1
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Fu B, Luo D, Li C, Feng Y, Liang W. Advances in micro-/nanorobots for cancer diagnosis and treatment: propulsion mechanisms, early detection, and cancer therapy. Front Chem 2025; 13:1537917. [PMID: 39981265 PMCID: PMC11839623 DOI: 10.3389/fchem.2025.1537917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 01/20/2025] [Indexed: 02/22/2025] Open
Abstract
In recent years, medical micro-/nanorobots (MNRs) have emerged as a promising technology for diagnosing and treating malignant tumors. MNRs enable precise, targeted actions at the cellular level, addressing several limitations of conventional cancer diagnosis and treatment, such as insufficient early diagnosis, nonspecific drug delivery, and chemoresistance. This review provides an in-depth discussion of the propulsion mechanisms of MNRs, including chemical fuels, external fields (light, ultrasound, magnetism), biological propulsion, and hybrid methods, highlighting their respective advantages and limitations. Additionally, we discuss novel approaches for tumor diagnosis, precision surgery, and drug delivery, emphasizing their potential clinical applications. Despite significant advancements, challenges such as biocompatibility, propulsion efficiency, and clinical translation persist. This review examines the current state of MNR applications and outlines future directions for their development, with the aim of enhancing their diagnostic and therapeutic efficacy and facilitating their integration into clinical practice.
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Affiliation(s)
- Baiyang Fu
- Department of Breast Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dan Luo
- College of Automotive and Mechanical Engineering, Harbin Cambridge University, Harbin, China
| | - Chao Li
- Department of Rheumatology and Immunology, Daqing Oilfield General Hospital, Daqing, China
| | - Yiwen Feng
- Key Laboratory for Micro/Nano Technology and System of Liaoning Province, Dalian University of Technology, Dalian, China
| | - Wenlong Liang
- Department of Breast Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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2
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Yang H, Lu Y, Ding Y, Zhang Z, Ren A, Wang H, Wang X, Li J, Zhang S, Xie H. A microgripper based on electrothermal Al-SiO 2 bimorphs. MICROSYSTEMS & NANOENGINEERING 2024; 10:195. [PMID: 39681569 DOI: 10.1038/s41378-024-00821-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 08/14/2024] [Accepted: 09/03/2024] [Indexed: 12/18/2024]
Abstract
Microgrippers are essential for assembly and manipulation at the micro- and nano-scales, facilitating important applications in microelectronics, MEMS, and biomedical engineering. To guarantee the safe handling of delicate materials and micro-objects, a microgripper needs to be designed to operate with exceptional precision, rapid response, user-friendly operation, strong reliability, and low power consumption. In this study, we develop an electrothermal actuated microgripper with Al-SiO2 bimorphs as the primary structural element. The fabricated microgripper naturally adopts a closed state due to process-induced residual stresses. The thermal expansion mismatch between Al and SiO2 allows for an easy transition of the microgripper between open and closed states by temperature control. Experimental data reveal that the microgripper can achieve impressive deformability, bending over 100 degrees at just 5 V, and responding within 10 ms. Its capability to handle micro-objects is verified using polymethyl methacrylate (PMMA) microbeads and its gripping strength is quantitatively assessed. It is demonstrated that the microgripper holding a microbead with a diameter of 400 μm and a weight of 0.1 mg can withstand an average acceleration of 35 g during vibration test and over 1600 g in impact tests, highlighting its exceptional grasping performance. Additionally, the "pick-and-place" task for handling and positioning solder beads (0.25 mg for each bead) with diameters of 400 μm on a bulk silicon inductor chip has been successfully completed. This unique microgripper is anticipated to be highly beneficial for various micro-assembly and micromanipulation applications, particularly in the field of electronic packaging.
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Affiliation(s)
- Hengzhang Yang
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China
| | - Yao Lu
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China
- Chongqing Institute of Microelectronics and Microsystems, Beijing Institute of Technology, Chongqing, China
| | - Yingtao Ding
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China
| | - Ziyue Zhang
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China
| | - Anrun Ren
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China
| | - Haopu Wang
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China
| | - Xiaoyi Wang
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China
- Chongqing Institute of Microelectronics and Microsystems, Beijing Institute of Technology, Chongqing, China
| | - Jiafang Li
- School of Physics, Beijing Institute of Technology, Beijing, China
| | - Shuailong Zhang
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China.
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China.
- Chongqing Institute of Microelectronics and Microsystems, Beijing Institute of Technology, Chongqing, China.
- Zhengzhou Research Institute, Beijing Institute of Technology, Zhengzhou, China.
| | - Huikai Xie
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, China.
- Engineering Research Center of Integrated Acousto-opto-electronic Microsystems, Ministry of Education of China, Beijing, China.
- Chongqing Institute of Microelectronics and Microsystems, Beijing Institute of Technology, Chongqing, China.
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3
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Liu W, Alam R, Choi SY, Wan Y, Zhang R, Baraban E, Matoso A, Matlaga BR, Winoker JS, Gracias DH. Untethered Microgrippers for Biopsy in the Upper Urinary Tract. Adv Healthc Mater 2024; 13:e2401407. [PMID: 39101622 PMCID: PMC11584312 DOI: 10.1002/adhm.202401407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/26/2024] [Indexed: 08/06/2024]
Abstract
Untethered microrobots offer the possibility to perform medical interventions in anatomically complex and small regions in the body. Presently, it is necessary to access the upper urinary tract to diagnose and treat Upper Tract Urothelial Carcinoma (UTUC). Diagnostic and treatment challenges include ensuring adequate tissue sampling, accurately grading the disease, achieving completeness in endoscopic treatment, and consistently delivering medications to targeted sites. This work introduces microgrippers (µ-grippers) that are autonomously triggered by physiological temperature for biopsy in the upper urinary tract. The experiments demonstrated that µ-grippers can be deployed using standard ureteral catheters and maneuvered using an external magnetic field. The μ-grippers successfully biopsied tissue samples from ex vivo pig ureters, indicating that the thin-film bilayer springs' autonomous, physiologically triggered actuation exerts enough force to retrieve urinary tract tissue. The quality of these biopsy samples is sufficient for histopathological examination, including hematoxylin and eosin (H&E) and GATA3 immunohistochemical staining. Beyond biopsy applications, the µ-grippers' small size, wafer-scale fabrication, and multifunctionality suggest their potential for statistical sampling in the urinary tract. Experimental data and clinical reports underscore this potential through statistical simulations that compare the efficacy of µ-grippers with conventional tools, such as ureteroscopic forceps and baskets.
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Affiliation(s)
- Wangqu Liu
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Ridwan Alam
- The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Si Young Choi
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Yan Wan
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Ruili Zhang
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Ezra Baraban
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Andres Matoso
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Brian R Matlaga
- The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Jared S Winoker
- Smith Institute for Urology, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, 10075, USA
| | - David H Gracias
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
- Department of Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA
- Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
- Laboratory for Computational Sensing and Robotics (LCSR), Johns Hopkins University, Baltimore, MD, 21218, USA
- Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
- Center for MicroPhysiological Systems (MPS), Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
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4
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Dong X, Xiao B, Vu H, Lin H, Sitti M. Millimeter-scale soft capsules for sampling liquids in fluid-filled confined spaces. SCIENCE ADVANCES 2024; 10:eadp2758. [PMID: 39196937 PMCID: PMC11352903 DOI: 10.1126/sciadv.adp2758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 07/23/2024] [Indexed: 08/30/2024]
Abstract
Sampling liquids in small and confined spaces to retrieve chemicals and microbiomes could enable minimally invasive monitoring human physiological conditions for understanding disease development and allowing early screening. However, existing tools are either invasive or too large for sampling liquids in tortuous and narrow spaces. Here we report a fundamental liquid sampling mechanism that enables millimeter-scale soft capsules for sampling liquids in confined spaces. The miniature capsule is enabled by flexible magnetic valves and superabsorbent polymer, fully wirelessly controlled for on-demand fluid sampling. A group of miniature capsules could navigate in fluid-filled and confined spaces safely using a rolling locomotion. The integration of on-demand triggering, sampling, and sealing mechanism and the agile group locomotion allows us to demonstrate precise control of the soft capsules, navigating and sampling body fluids in a phantom and animal organ ex vivo, guided by ultrasound and x-ray medical imaging. The proposed mechanism and wirelessly controlled devices spur the next-generation technologies for minimally invasive disease diagnosis.
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Affiliation(s)
- Xiaoguang Dong
- Department of Mechanical Engineering, Vanderbilt University, Nashville, TN 37235, USA
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Boyang Xiao
- Department of Mechanical Engineering, Vanderbilt University, Nashville, TN 37235, USA
| | - Hieu Vu
- Department of Mechanical Engineering, Vanderbilt University, Nashville, TN 37235, USA
| | - Honglu Lin
- Department of Mechanical Engineering, Vanderbilt University, Nashville, TN 37235, USA
| | - Metin Sitti
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
- School of Medicine and College of Engineering, Koç University, 34450 Istanbul, Turkey
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5
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Gao R, Wang W, Wang Z, Fan Y, Zhang L, Sun J, Hong M, Pan M, Wu J, Mei Q, Wang Y, Qiao L, Liu J, Tong F. Hibernating/Awakening Nanomotors Promote Highly Efficient Cryopreservation by Limiting Ice Crystals. Adv Healthc Mater 2024:e2401833. [PMID: 39101314 DOI: 10.1002/adhm.202401833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/20/2024] [Indexed: 08/06/2024]
Abstract
The disruptions caused by ice crystal formation during the cryopreservation of cells and tissues can cause cell and tissue damage. Thus, preventing such damage during cryopreservation is an important but challenging goal. Here, a hibernating/awakening nanomotor with magnesium/palladium covering one side of a silica platform (Mg@Pd@SiO2) is proposed. This nanomotor is used in the cultivation of live NCM460 cells to demonstrate a new method to actively limit ice crystal formation and enable highly efficient cryopreservation. Cooling Mg@Pd@SiO2 in solution releases Mg2+/H2 and promotes the adsorption of H2 at multiple Pd binding sites on the cell surface to inhibit ice crystal formation and cell/tissue damage; additionally, the Pd adsorbs and stores H2 to form a hibernating nanomotor. During laser-mediated heating, the hibernating nanomotor is activated (awakened) and releases H2, which further suppresses recrystallization and decreases cell/tissue damage. These hibernating/awakening nanomotors have great potential for promoting highly efficient cryopreservation by inhibiting ice crystal formation.
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Affiliation(s)
- Rui Gao
- Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Weixin Wang
- Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Zhongchao Wang
- Institute of Cardiovascular Disease, Shanxi Medical University, Taiyuan, 030001, P. R. China
| | - Yapeng Fan
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, P. R. China
| | - Lin Zhang
- Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Jiahui Sun
- Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Miaofang Hong
- Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Min Pan
- Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Jianming Wu
- Education Ministry Key Laboratory of Medical Electrophysiology, Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, 646000, P. R. China
| | - Qibing Mei
- Education Ministry Key Laboratory of Medical Electrophysiology, Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, 646000, P. R. China
| | - Yini Wang
- Clinical Medical College, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Lingyan Qiao
- Clinical Medical College, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Jin Liu
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, P. R. China
| | - Fei Tong
- Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai, 264003, P. R. China
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6
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Mirzababaei S, Towery LAK, Kozminsky M. 3D and 4D assembly of functional structures using shape-morphing materials for biological applications. Front Bioeng Biotechnol 2024; 12:1347666. [PMID: 38605991 PMCID: PMC11008679 DOI: 10.3389/fbioe.2024.1347666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 02/01/2024] [Indexed: 04/13/2024] Open
Abstract
3D structures are crucial to biological function in the human body, driving interest in their in vitro fabrication. Advances in shape-morphing materials allow the assembly of 3D functional materials with the ability to modulate the architecture, flexibility, functionality, and other properties of the final product that suit the desired application. The principles of these techniques correspond to the principles of origami and kirigami, which enable the transformation of planar materials into 3D structures by folding, cutting, and twisting the 2D structure. In these approaches, materials responding to a certain stimulus will be used to manufacture a preliminary structure. Upon applying the stimuli, the architecture changes, which could be considered the fourth dimension in the manufacturing process. Here, we briefly summarize manufacturing techniques, such as lithography and 3D printing, that can be used in fabricating complex structures based on the aforementioned principles. We then discuss the common architectures that have been developed using these methods, which include but are not limited to gripping, rolling, and folding structures. Then, we describe the biomedical applications of these structures, such as sensors, scaffolds, and minimally invasive medical devices. Finally, we discuss challenges and future directions in using shape-morphing materials to develop biomimetic and bioinspired designs.
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Affiliation(s)
- Soheyl Mirzababaei
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, United States
| | - Lily Alyssa Kera Towery
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, United States
| | - Molly Kozminsky
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, United States
- Nanovaccine Institute, Iowa State University, Ames, IA, United States
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7
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Mandal A, Chatterjee K. 4D printing for biomedical applications. J Mater Chem B 2024; 12:2985-3005. [PMID: 38436200 DOI: 10.1039/d4tb00006d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2024]
Abstract
While three-dimensional (3D) printing excels at fabricating static constructs, it fails to emulate the dynamic behavior of native tissues or the temporal programmability desired for medical devices. Four-dimensional (4D) printing is an advanced additive manufacturing technology capable of fabricating constructs that can undergo pre-programmed changes in shape, property, or functionality when exposed to specific stimuli. In this Perspective, we summarize the advances in materials chemistry, 3D printing strategies, and post-printing methodologies that collectively facilitate the realization of temporal dynamics within 4D-printed soft materials (hydrogels, shape-memory polymers, liquid crystalline elastomers), ceramics, and metals. We also discuss and present insights about the diverse biomedical applications of 4D printing, including tissue engineering and regenerative medicine, drug delivery, in vitro models, and medical devices. Finally, we discuss the current challenges and emphasize the importance of an application-driven design approach to enable the clinical translation and widespread adoption of 4D printing.
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Affiliation(s)
- Arkodip Mandal
- Department of Materials Engineering, Indian Institute of Science, Bengaluru, Karnataka 560012, India.
| | - Kaushik Chatterjee
- Department of Materials Engineering, Indian Institute of Science, Bengaluru, Karnataka 560012, India.
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8
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Hu X, Zhou Y, Li M, Wu J, He G, Jiao N. Catheter-Assisted Bioinspired Adhesive Magnetic Soft Millirobot for Drug Delivery. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2306510. [PMID: 37880878 DOI: 10.1002/smll.202306510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/26/2023] [Indexed: 10/27/2023]
Abstract
Soft millirobots have evolved into various therapeutic applications in the medical field, including for vascular dredging, cell transportation, and drug delivery, owing to adaptability to their surroundings. However, most soft millirobots cannot quickly enter, retrieve, and maintain operations in their original locations after removing the external actuation field. This study introduces a soft magnetic millirobot for targeted medicine delivery that can be transported into the body through a catheter and anchored to the tissues. The millirobot has a bilayer adhesive body with a mussel-inspired hydrogel layer and an octopus-inspired magnetic structural layer. It completes entry and retrieval with the assistance of a medical catheter based on the difference between the adhesion of the hydrogel layer in air and water. The millirobot can operate in multiple modes of motion under external magnetic fields and underwater tissue adhesion after self-unfolding with the structural layer. The adaptability and recyclability of the millirobots are demonstrated using a stomach model. Combined with ultrasound (US) imaging, operational feasibility within organisms is shown in isolated small intestines. In addition, a highly efficient targeted drug delivery is confirmed using a fluorescence imaging system. Therefore, the proposed soft magnetic millirobots have significant potential for medical applications.
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Affiliation(s)
- Xingyue Hu
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- Institutes for Robotics and Intelligent Manufacturing, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yuting Zhou
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- Institutes for Robotics and Intelligent Manufacturing, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Mengyue Li
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- Institutes for Robotics and Intelligent Manufacturing, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Junfeng Wu
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- Institutes for Robotics and Intelligent Manufacturing, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Guannan He
- Department of Anesthesiology, The First Hospital, China Medical University, Shenyang, Liaoning, 110001, China
| | - Niandong Jiao
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
- Institutes for Robotics and Intelligent Manufacturing, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China
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9
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Zhou H, Zhang S, Liu Z, Chi B, Li J, Wang Y. Untethered Microgrippers for Precision Medicine. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2305805. [PMID: 37941516 DOI: 10.1002/smll.202305805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 10/07/2023] [Indexed: 11/10/2023]
Abstract
Microgrippers, a branch of micro/nanorobots, refer to motile miniaturized machines that are of a size in the range of several to hundreds of micrometers. Compared with tethered grippers or other microscopic diagnostic and surgical equipment, untethered microgrippers play an indispensable role in biomedical applications because of their characteristics such as miniaturized size, dexterous shape tranformation, and controllable motion, which enables the microgrippers to enter hard-to-reach regions to execute specific medical tasks for disease diagnosis and treatment. To date, numerous medical microgrippers are developed, and their potential in cell manipulation, targeted drug delivery, biopsy, and minimally invasive surgery are explored. To achieve controlled locomotion and efficient target-oriented actions, the materials, size, microarchitecture, and morphology of microgrippers shall be deliberately designed. In this review, the authors summarizes the latest progress in untethered micrometer-scale grippers. The working mechanisms of shape-morphing and actuation methods for effective movement are first introduced. Then, the design principle and state-of-the-art fabrication techniques of microgrippers are discussed. Finally, their applications in the precise medicine are highlighted, followed by offering future perspectives for the development of untethered medical microgrippers.
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Affiliation(s)
- Huaijuan Zhou
- Advanced Research Institute of Multidisciplinary Sciences, Beijing Institute of Technology, Beijing, 100081, China
| | - Shengchang Zhang
- School of Medical Technology, Beijing Institute of Technology, Beijing, 100081, China
| | - Zijian Liu
- School of Medical Technology, Beijing Institute of Technology, Beijing, 100081, China
| | - Bowen Chi
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
| | - Jinhua Li
- School of Medical Technology, Beijing Institute of Technology, Beijing, 100081, China
| | - Yilong Wang
- School of Medical Technology, Beijing Institute of Technology, Beijing, 100081, China
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
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10
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Dong H, Lin J, Tao Y, Jia Y, Sun L, Li WJ, Sun H. AI-enhanced biomedical micro/nanorobots in microfluidics. LAB ON A CHIP 2024; 24:1419-1440. [PMID: 38174821 DOI: 10.1039/d3lc00909b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Human beings encompass sophisticated microcirculation and microenvironments, incorporating a broad spectrum of microfluidic systems that adopt fundamental roles in orchestrating physiological mechanisms. In vitro recapitulation of human microenvironments based on lab-on-a-chip technology represents a critical paradigm to better understand the intricate mechanisms. Moreover, the advent of micro/nanorobotics provides brand new perspectives and dynamic tools for elucidating the complex process in microfluidics. Currently, artificial intelligence (AI) has endowed micro/nanorobots (MNRs) with unprecedented benefits, such as material synthesis, optimal design, fabrication, and swarm behavior. Using advanced AI algorithms, the motion control, environment perception, and swarm intelligence of MNRs in microfluidics are significantly enhanced. This emerging interdisciplinary research trend holds great potential to propel biomedical research to the forefront and make valuable contributions to human health. Herein, we initially introduce the AI algorithms integral to the development of MNRs. We briefly revisit the components, designs, and fabrication techniques adopted by robots in microfluidics with an emphasis on the application of AI. Then, we review the latest research pertinent to AI-enhanced MNRs, focusing on their motion control, sensing abilities, and intricate collective behavior in microfluidics. Furthermore, we spotlight biomedical domains that are already witnessing or will undergo game-changing evolution based on AI-enhanced MNRs. Finally, we identify the current challenges that hinder the practical use of the pioneering interdisciplinary technology.
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Affiliation(s)
- Hui Dong
- School of Mechanical Engineering and Automation, Fuzhou University, Fuzhou, China.
- School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, China
- State Key Laboratory of Robotics and System, Harbin Institute of Technology, Harbin, China
| | - Jiawen Lin
- School of Mechanical Engineering and Automation, Fuzhou University, Fuzhou, China.
| | - Yihui Tao
- Department of Automation Control and System Engineering, University of Sheffield, Sheffield, UK
| | - Yuan Jia
- Sino-German College of Intelligent Manufacturing, Shenzhen Technology University, Shenzhen, China
| | - Lining Sun
- School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, China
- State Key Laboratory of Robotics and System, Harbin Institute of Technology, Harbin, China
| | - Wen Jung Li
- Department of Mechanical Engineering, City University of Hong Kong, Hong Kong, China
| | - Hao Sun
- School of Mechanical Engineering and Automation, Fuzhou University, Fuzhou, China.
- School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, China
- Research Center of Aerospace Mechanism and Control, Harbin Institute of Technology, Harbin, China
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11
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Sun T, Chen J, Zhang J, Zhao Z, Zhao Y, Sun J, Chang H. Application of micro/nanorobot in medicine. Front Bioeng Biotechnol 2024; 12:1347312. [PMID: 38333078 PMCID: PMC10850249 DOI: 10.3389/fbioe.2024.1347312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 01/02/2024] [Indexed: 02/10/2024] Open
Abstract
The development of micro/nanorobots and their application in medical treatment holds the promise of revolutionizing disease diagnosis and treatment. In comparison to conventional diagnostic and treatment methods, micro/nanorobots exhibit immense potential due to their small size and the ability to penetrate deep tissues. However, the transition of this technology from the laboratory to clinical applications presents significant challenges. This paper provides a comprehensive review of the research progress in micro/nanorobotics, encompassing biosensors, diagnostics, targeted drug delivery, and minimally invasive surgery. It also addresses the key issues and challenges facing this technology. The fusion of micro/nanorobots with medical treatments is poised to have a profound impact on the future of medicine.
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Affiliation(s)
- Tianhao Sun
- Department of Thoracic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Jingyu Chen
- Department of Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Jiayang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhihong Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yiming Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Jingxue Sun
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hao Chang
- Department of Thoracic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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12
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Paul N, Zhang L, Lei S, Huang D, Wang L, Cheng Z, Zeng M. Ligand-Directed Shape Reconfiguration in Inorganic Materials. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2305460. [PMID: 37726244 DOI: 10.1002/smll.202305460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 09/05/2023] [Indexed: 09/21/2023]
Abstract
Polymer elastomers with reversible shape-changing capability have led to significant development of artificial muscles, functional devices, and soft robots. By contrast, reversible shape transformation of inorganic nanoparticles is notoriously challenging due to their relatively rigid lattice structure. Here, the authors demonstrate the synthesis of shape-changing nanoparticles via an asymmetrical surface functionalization process. Various ligands are investigated, revealing the essential role of steric hindrance from the functional groups. By controlling the unbalanced structural hindrance on the surface, the as-prepared clay nanoparticles can transform their shape in a fast, facile, and reversible manner. In addition, such flexible morphology-controlled mechanism provides a platform for developing self-propelled shape-shifting nanocollectors. Owing to the ion-exchanging capability of clay, these self-propelled nanoswimmers (NS) are able to autonomously adsorb rare earth elements with ultralow concentration, indicating the feasibility of using naturally occurring materials for self-powered nanomachine.
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Affiliation(s)
- Nishat Paul
- Department of Chemical Engineering, Texas Tech University, Lubbock, TX, 79409, USA
| | - Lecheng Zhang
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843, USA
| | - Shijun Lei
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843, USA
| | - Dali Huang
- Department of Materials Science & Engineering, Texas A&M University, 3003 TAMU, College Station, TX, 77843, USA
| | - Ling Wang
- School of Materials Science and Engineering, Tianjin University, Tianjin, 300350, China
| | - Zhengdong Cheng
- College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China
| | - Minxiang Zeng
- Department of Chemical Engineering, Texas Tech University, Lubbock, TX, 79409, USA
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13
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Moon S. A Planar-Type Micro-Biopsy Tool for a Capsule-Type Endoscope Using a One-Step Nickel Electroplating Process. MICROMACHINES 2023; 14:1900. [PMID: 37893337 PMCID: PMC10609584 DOI: 10.3390/mi14101900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/23/2023] [Accepted: 10/02/2023] [Indexed: 10/29/2023]
Abstract
Millimeter-scale biopsy tools combined with an endoscope instrument have been widely used for minimal invasive surgery and medical diagnosis. Recently, a capsule-type endoscope was developed, which requires micromachining to fabricate micro-scale biopsy tools that have a sharp tip and other complex features, e.g., nanometer-scale end-tip sharpness and a complex scalpel design. However, conventional machining approaches are not cost-effective for mass production and cannot fabricate the micrometer-scale features needed for biopsy tools. Here, we demonstrate an electroplated nickel micro-biopsy tool which features a planar shape and is suitable to be equipped with a capsule-type endoscope. Planar-type micro-biopsy tools are designed, fabricated, and evaluated through in vitro tissue dissection experiments. Various micro-biopsy tools with a long shaft and sharp tip can be easily fabricated using a thick photoresist (SU8) mold via a simple one-step lithography and nickel electroplating process. The characteristics of various micro-biopsy tool design features, including a tip taper angle, different tool geometries, and a cutting scalpel, are evaluated for efficient tissue extraction from mice intestine. These fabricated biopsy tools have shown appropriate strength and sharpness with a sufficient amount of tissue extraction for clinical applications, e.g., cancer tissue biopsy. These micro-scale biopsy tools could be easily integrated with a capsule-type endoscope and conventional forceps.
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Affiliation(s)
- Sangjun Moon
- Department of Mechanical Convergence Engineering, Gyeongsang National University, Changwon 51391, Gyeongsangnam-do, Republic of Korea; ; Tel.: +82-55-250-7304; Fax: +82-55-250-7399
- Cyberneticsimagingsystems Co., Ltd., Changwon 51391, Gyeongsangnam-do, Republic of Korea
- Department of Mechanical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
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14
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Shivalkar S, Roy A, Chaudhary S, Samanta SK, Chowdhary P, Sahoo AK. Strategies in design of self-propelling hybrid micro/nanobots for bioengineering applications. Biomed Mater 2023; 18:062003. [PMID: 37703889 DOI: 10.1088/1748-605x/acf975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 09/13/2023] [Indexed: 09/15/2023]
Abstract
Micro/nanobots are integrated devices developed from engineered nanomaterials that have evolved significantly over the past decades. They can potentially be pre-programmed to operate robustly at numerous hard-to-reach organ/tissues/cellular sites for multiple bioengineering applications such as early disease diagnosis, precision surgeries, targeted drug delivery, cancer therapeutics, bio-imaging, biomolecules isolation, detoxification, bio-sensing, and clearing up clogged arteries with high soaring effectiveness and minimal exhaustion of power. Several techniques have been introduced in recent years to develop programmable, biocompatible, and energy-efficient micro/nanobots. Therefore, the primary focus of most of these techniques is to develop hybrid micro/nanobots that are an optimized combination of purely synthetic or biodegradable bots suitable for the execution of user-defined tasks more precisely and efficiently. Recent progress has been illustrated here as an overview of a few of the achievable construction principles to be used to make biomedical micro/nanobots and explores the pivotal ventures of nanotechnology-moderated development of catalytic autonomous bots. Furthermore, it is also foregrounding their advancement offering an insight into the recent trends and subsequent prospects, opportunities, and challenges involved in the accomplishments of the effective multifarious bioengineering applications.
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Affiliation(s)
- Saurabh Shivalkar
- Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, UP, India
| | - Anwesha Roy
- Department of Biotechnology, Heritage Institute of Technology, Kolkata, West Bengal, India
| | - Shrutika Chaudhary
- Department of Biotechnology, Delhi Technological University, Delhi, India
| | - Sintu Kumar Samanta
- Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, UP, India
| | - Pallabi Chowdhary
- Department of Biotechnology, M.S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India
| | - Amaresh Kumar Sahoo
- Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, UP, India
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15
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Li J, Zhou H, Liu C, Zhang S, Du R, Deng Y, Zou X. Biomembrane‐inspired design of medical micro/nanorobots: From cytomembrane stealth cloaks to cellularized Trojan horses. AGGREGATE 2023; 4. [DOI: 10.1002/agt2.359] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
AbstractMicro/nanorobots are promising for a wide range of biomedical applications (such as targeted tumor, thrombus, and infection therapies in hard‐to‐reach body sites) because of their tiny size and high maneuverability through the actuation of external fields (e.g., magnetic field, light, ultrasound, electric field, and/or heat). However, fully synthetic micro/nanorobots as foreign objects are susceptible to phagocytosis and clearance by diverse phagocytes. To address this issue, researchers have attempted to develop various cytomembrane‐camouflaged micro/nanorobots by two means: (1) direct coating of micro/nanorobots with cytomembranes derived from living cells and (2) the swallowing of micro/nanorobots by living immunocytes via phagocytosis. The camouflaging with cytomembranes or living immunocytes not only protects micro/nanorobots from phagocytosis, but also endows them with new characteristics or functionalities, such as prolonging propulsion in biofluids, targeting diseased areas, or neutralizing bacterial toxins. In this review, we comprehensively summarize the recent advances and developments of cytomembrane‐camouflaged medical micro/nanorobots. We first discuss how cytomembrane coating nanotechnology has been employed to engineer synthetic nanomaterials, and then we review in detail how cytomembrane camouflage tactic can be exploited to functionalize micro/nanorobots. We aim to bridge the gap between cytomembrane‐cloaked micro/nanorobots and nanomaterials and to provide design guidance for developing cytomembrane‐camouflaged micro/nanorobots.
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Affiliation(s)
- Jinhua Li
- School of Medical Technology Beijing Institute of Technology Beijing China
| | - Huaijuan Zhou
- Advanced Research Institute of Multidisciplinary Sciences Beijing Institute of Technology Beijing China
| | - Chun Liu
- Center for Translational Medicine Precision Medicine Institute The First Affiliated Hospital of Sun Yat‐sen University Guangzhou China
- Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spinal Surgery The First Affiliated Hospital of Sun Yat‐sen University Guangzhou China
| | - Shuailong Zhang
- School of Mechatronical Engineering Beijing Institute of Technology Beijing China
| | - Ran Du
- School of Materials Science & Engineering Key Laboratory of High Energy Density Materials of the Ministry of Education Beijing Institute of Technology Beijing China
| | - Yulin Deng
- School of Life Science Beijing Institute of Technology Beijing China
| | - Xuenong Zou
- Center for Translational Medicine Precision Medicine Institute The First Affiliated Hospital of Sun Yat‐sen University Guangzhou China
- Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spinal Surgery The First Affiliated Hospital of Sun Yat‐sen University Guangzhou China
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16
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Bo R, Xu S, Yang Y, Zhang Y. Mechanically-Guided 3D Assembly for Architected Flexible Electronics. Chem Rev 2023; 123:11137-11189. [PMID: 37676059 PMCID: PMC10540141 DOI: 10.1021/acs.chemrev.3c00335] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Indexed: 09/08/2023]
Abstract
Architected flexible electronic devices with rationally designed 3D geometries have found essential applications in biology, medicine, therapeutics, sensing/imaging, energy, robotics, and daily healthcare. Mechanically-guided 3D assembly methods, exploiting mechanics principles of materials and structures to transform planar electronic devices fabricated using mature semiconductor techniques into 3D architected ones, are promising routes to such architected flexible electronic devices. Here, we comprehensively review mechanically-guided 3D assembly methods for architected flexible electronics. Mainstream methods of mechanically-guided 3D assembly are classified and discussed on the basis of their fundamental deformation modes (i.e., rolling, folding, curving, and buckling). Diverse 3D interconnects and device forms are then summarized, which correspond to the two key components of an architected flexible electronic device. Afterward, structure-induced functionalities are highlighted to provide guidelines for function-driven structural designs of flexible electronics, followed by a collective summary of their resulting applications. Finally, conclusions and outlooks are given, covering routes to achieve extreme deformations and dimensions, inverse design methods, and encapsulation strategies of architected 3D flexible electronics, as well as perspectives on future applications.
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Affiliation(s)
- Renheng Bo
- Applied
Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, 100084 Beijing, People’s Republic of China
- Laboratory
of Flexible Electronics Technology, Tsinghua
University, 100084 Beijing, People’s Republic
of China
| | - Shiwei Xu
- Applied
Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, 100084 Beijing, People’s Republic of China
- Laboratory
of Flexible Electronics Technology, Tsinghua
University, 100084 Beijing, People’s Republic
of China
| | - Youzhou Yang
- Applied
Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, 100084 Beijing, People’s Republic of China
- Laboratory
of Flexible Electronics Technology, Tsinghua
University, 100084 Beijing, People’s Republic
of China
| | - Yihui Zhang
- Applied
Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, 100084 Beijing, People’s Republic of China
- Laboratory
of Flexible Electronics Technology, Tsinghua
University, 100084 Beijing, People’s Republic
of China
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17
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Achouri K, Chung M, Kiselev A, Martin OJF. Multipolar Pseudochirality-Induced Optical Torque. ACS PHOTONICS 2023; 10:3275-3282. [PMID: 37743946 PMCID: PMC10515695 DOI: 10.1021/acsphotonics.3c00696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Indexed: 09/26/2023]
Abstract
It has been observed that achiral nanoparticles, such as flat helices, may be subjected to an optical torque even when illuminated by normally incident linearly polarized light. However, the origin of this fascinating phenomenon has so far remained mostly unexplained. We therefore propose an exhaustive discussion that provides a clear and rigorous explanation for the existence of such a torque. Using multipolar theory and taking into account nonlocal interactions, we find that this torque stems from multipolar pseudochiral responses that generate both spin and orbital angular momenta. We also show that the nature of these peculiar responses makes them particularly dependent on the asymmetry of the particles. By elucidating the origin of this type of torque, this work may prove instrumental for the design of high-performance nano-rotors.
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Affiliation(s)
- Karim Achouri
- Nanophotonics and Metrology Laboratory, Institute of Electrical and Microengineering, École
Polytechnique Fédérale de Lausanne, Route Cantonale, 1015 Lausanne, Switzerland
| | - Mintae Chung
- Nanophotonics and Metrology Laboratory, Institute of Electrical and Microengineering, École
Polytechnique Fédérale de Lausanne, Route Cantonale, 1015 Lausanne, Switzerland
| | - Andrei Kiselev
- Nanophotonics and Metrology Laboratory, Institute of Electrical and Microengineering, École
Polytechnique Fédérale de Lausanne, Route Cantonale, 1015 Lausanne, Switzerland
| | - Olivier J. F. Martin
- Nanophotonics and Metrology Laboratory, Institute of Electrical and Microengineering, École
Polytechnique Fédérale de Lausanne, Route Cantonale, 1015 Lausanne, Switzerland
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18
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Li Z, Wang K, Hou C, Li C, Zhang F, Ren W, Dong L, Zhao J. Self-sensing intelligent microrobots for noninvasive and wireless monitoring systems. MICROSYSTEMS & NANOENGINEERING 2023; 9:102. [PMID: 37565051 PMCID: PMC10409863 DOI: 10.1038/s41378-023-00574-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 06/01/2023] [Accepted: 07/10/2023] [Indexed: 08/12/2023]
Abstract
Microrobots have garnered tremendous attention due to their small size, flexible movement, and potential for various in situ treatments. However, functional modification of microrobots has become crucial for their interaction with the environment, except for precise motion control. Here, a novel artificial intelligence (AI) microrobot is designed that can respond to changes in the external environment without an onboard energy supply and transmit signals wirelessly in real time. The AI microrobot can cooperate with external electromagnetic imaging equipment and enhance the local radiofrequency (RF) magnetic field to achieve a large penetration sensing depth and a high spatial resolution. The working ranges are determined by the structure of the sensor circuit, and the corresponding enhancement effect can be modulated by the conductivity and permittivity of the surrounding environment, reaching ~560 times at most. Under the control of an external magnetic field, the magnetic tail can actuate the microrobotic agent to move accurately, with great potential to realize in situ monitoring in different places in the human body, almost noninvasively, especially around potential diseases, which is of great significance for early disease discovery and accurate diagnosis. In addition, the compatible fabrication process can produce swarms of functional microrobots. The findings highlight the feasibility of the self-sensing AI microrobots for the development of in situ diagnosis or even treatment according to sensing signals.
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Affiliation(s)
- Zhongyi Li
- School of Mechatronical Engineering, Beijing Institute of Technology, 100081 Beijing, China
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, 100081 Beijing, China
| | - Kun Wang
- Department of Biomedical Engineering, City University of Hong Kong, 999077 Kowloon Tong, Hong Kong China
| | - Chaojian Hou
- Department of Biomedical Engineering, City University of Hong Kong, 999077 Kowloon Tong, Hong Kong China
| | - Chunyang Li
- School of Mechatronical Engineering, Beijing Institute of Technology, 100081 Beijing, China
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, 100081 Beijing, China
| | - Fanqing Zhang
- School of Mechatronical Engineering, Beijing Institute of Technology, 100081 Beijing, China
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, 100081 Beijing, China
| | - Wu Ren
- School of Integrated Circuits and Electronics, Beijing Institute of Technology, 100081 Beijing, China
| | - Lixin Dong
- Department of Biomedical Engineering, City University of Hong Kong, 999077 Kowloon Tong, Hong Kong China
| | - Jing Zhao
- School of Mechatronical Engineering, Beijing Institute of Technology, 100081 Beijing, China
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, 100081 Beijing, China
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19
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Zhang B, Zhu L, Pan H, Cai L. Biocompatible smart micro/nanorobots for active gastrointestinal tract drug delivery. Expert Opin Drug Deliv 2023; 20:1427-1441. [PMID: 37840310 DOI: 10.1080/17425247.2023.2270915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/11/2023] [Indexed: 10/17/2023]
Abstract
INTRODUCTION Oral delivery is the most commonly used route of drug administration owing to good patient compliance. However, the gastrointestinal (GI) tract contains multiple physiological barriers that limit the absorption efficiency of conventional passive delivery systems resulting in a low drug concentration reaching the diseased sites. Micro/nanorobots can convert energy to self-propulsive force, providing a novel platform to actively overcome GI tract barriers for noninvasive drug delivery and treatment. AREAS COVERED In this review, we first describe the microenvironments and barriers in the different compartments of the GI tract. Afterward, the applications of micro/nanorobots to overcome GI tract barriers for active drug delivery are highlighted and discussed. Finally, we summarize and discuss the challenges and future prospects of micro/nanorobots for further clinical applications. EXPERT OPINION Micro/nanorobots with the ability to autonomously propel themselves and to load, transport, and release payloads on demand are ideal carriers for active oral drug delivery. Although there are many challenges to be addressed, micro/nanorobots have great potential to introduce a new era of drug delivery for precision therapy.
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Affiliation(s)
- Baozhen Zhang
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, China
- Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Lizhen Zhu
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, China
| | - Hong Pan
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, China
| | - Lintao Cai
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, China
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20
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Liu W, Choi SJ, George D, Li L, Zhong Z, Zhang R, Choi SY, Selaru FM, Gracias DH. Untethered shape-changing devices in the gastrointestinal tract. Expert Opin Drug Deliv 2023; 20:1801-1822. [PMID: 38044866 PMCID: PMC10872387 DOI: 10.1080/17425247.2023.2291450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 12/01/2023] [Indexed: 12/05/2023]
Abstract
INTRODUCTION Advances in microfabrication, automation, and computer engineering seek to revolutionize small-scale devices and machines. Emerging trends in medicine point to smart devices that emulate the motility, biosensing abilities, and intelligence of cells and pathogens that inhabit the human body. Two important characteristics of smart medical devices are the capability to be deployed in small conduits, which necessitates being untethered, and the capacity to perform mechanized functions, which requires autonomous shape-changing. AREAS COVERED We motivate the need for untethered shape-changing devices in the gastrointestinal tract for drug delivery, diagnosis, and targeted treatment. We survey existing structures and devices designed and utilized across length scales from the macro to the sub-millimeter. These devices range from triggerable pre-stressed thin film microgrippers and spring-loaded devices to shape-memory and differentially swelling structures. EXPERT OPINION Recent studies demonstrate that when fully enabled, tether-free and shape-changing devices, especially at sub-mm scales, could significantly advance the diagnosis and treatment of GI diseases ranging from cancer and inflammatory bowel disease (IBD) to irritable bowel syndrome (IBS) by improving treatment efficacy, reducing costs, and increasing medication compliance. We discuss the challenges and possibilities associated with ensuring safe, reliable, and autonomous operation of these smart devices.
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Affiliation(s)
- Wangqu Liu
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Soo Jin Choi
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Derosh George
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Ling Li
- Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Zijian Zhong
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Ruili Zhang
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Si Young Choi
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Florin M. Selaru
- Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - David H. Gracias
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
- Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA
- Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Laboratory for Computational Sensing and Robotics (LCSR), Johns Hopkins University, Baltimore, MD 21218, USA
- Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
- Center for MicroPhysiological Systems (MPS), Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
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21
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Heunis CM, Wang Z, de Vente G, Misra S, Venkiteswaran VK. A Magnetic Bio-Inspired Soft Carrier as a Temperature-Controlled Gastrointestinal Drug Delivery System. Macromol Biosci 2023; 23:e2200559. [PMID: 36945731 DOI: 10.1002/mabi.202200559] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/14/2023] [Indexed: 03/23/2023]
Abstract
Currently, gastrointestinal bleeding in the colon wall and the small bowel is diagnosed and treated with endoscopes. However, the locations of this condition are often problematic to treat using traditional flexible and tethered tools. New studies commonly consider untethered devices for solving this problem. However, there still exists a gap in the extant literature, and more research is needed to diagnose and deliver drugs in the lower gastrointestinal tract using soft robotic carriers. This paper discusses the development of an untethered, magnetically-responsive bio-inspired soft carrier. A molding process is utilized to produce prototypes from Diisopropylidene-1,6-diphenyl-1,6-hexanediol-based Polymer with Ethylene Glycol Dimethacrylate (DiAPLEX) MP-3510 - a shape memory polymer with a low transition temperature to enable the fabrication of these carriers. The soft carrier design is validated through simulation results of deformation caused by magnetic elements embedded in the carrier in response to an external field. The thermal responsiveness of the fabricated prototype carriers is assessed ex vivo and in a phantom. The results indicate a feasible design capable of administering drugs to a target inside a phantom of a large intestine. The soft carrier introduces a method for the controlled release of drugs by utilizing the rubbery modulus of the polymer and increasing the recovery force through magnetic actuation.
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Affiliation(s)
- Christoff M Heunis
- Surgical Robotics Laboratory, Department of Biomechanical Engineering, University of Twente, Enschede, 7500 AE, The Netherlands
| | - Zhuoyue Wang
- Department of Biomedical Engineering, University of Groningen and University Medical Centre Groningen, Groningen, 9713 GZ, The Netherlands
| | - Gerko de Vente
- Surgical Robotics Laboratory, Department of Biomechanical Engineering, University of Twente, Enschede, 7500 AE, The Netherlands
| | - Sarthak Misra
- Surgical Robotics Laboratory, Department of Biomechanical Engineering, University of Twente, Enschede, 7500 AE, The Netherlands
- Department of Biomedical Engineering, University of Groningen and University Medical Centre Groningen, Groningen, 9713 GZ, The Netherlands
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22
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Yan J, Zhang Y, Liu Z, Wang J, Xu J, Yu L. Ultracompact single-nanowire-morphed grippers driven by vectorial Lorentz forces for dexterous robotic manipulations. Nat Commun 2023; 14:3786. [PMID: 37355640 DOI: 10.1038/s41467-023-39524-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 06/16/2023] [Indexed: 06/26/2023] Open
Abstract
Ultracompact and soft pairwise grippers, capable of swift large-amplitude multi-dimensional maneuvering, are widely needed for high-precision manipulation, assembly and treatment of microscale objects. In this work, we demonstrate the simplest construction of such robotic structures, shaped via a single-nanowire-morphing and powered by geometry-tailored Lorentz vectorial forces. This has been accomplished via a designable folding growth of ultralong and ultrathin silicon NWs into single and nested omega-ring structures, which can then be suspended upon electrode frames and coated with silver metal layer to carry a passing current along geometry-tailored pathway. Within a magnetic field, the grippers can be driven by the Lorentz forces to demonstrate swift large-amplitude maneuvers of grasping, flapping and twisting of microscale objects, as well as high-frequency or even resonant vibrations to overcome sticky van de Waals forces in microscale for a reliable releasing of carried payloads. More sophisticated and functional teamwork of mutual alignment, precise passing and selective light-emitting-diode unit testing and installation were also successfully accomplished via pairwise gripper collaborations. This single-nanowire-morphing strategy provides an ideal platform to rapidly design, construct and prototype a wide range of advanced ultracompact nanorobotic, mechanical sensing and biological manipulation functionalities.
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Affiliation(s)
- Jiang Yan
- School of Electronic Science and Engineering, National Laboratory of Solid-State Microstructures, Nanjing University, 210023, Nanjing, China
| | - Ying Zhang
- School of Electronic Science and Engineering, National Laboratory of Solid-State Microstructures, Nanjing University, 210023, Nanjing, China
| | - Zongguang Liu
- School of Electronic Science and Engineering, National Laboratory of Solid-State Microstructures, Nanjing University, 210023, Nanjing, China.
| | - Junzhuan Wang
- School of Electronic Science and Engineering, National Laboratory of Solid-State Microstructures, Nanjing University, 210023, Nanjing, China
| | - Jun Xu
- School of Electronic Science and Engineering, National Laboratory of Solid-State Microstructures, Nanjing University, 210023, Nanjing, China
| | - Linwei Yu
- School of Electronic Science and Engineering, National Laboratory of Solid-State Microstructures, Nanjing University, 210023, Nanjing, China.
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Abstract
Untethered robots in the size range of micro/nano-scale offer unprecedented access to hard-to-reach areas of the body. In these challenging environments, autonomous task completion capabilities of micro/nanorobots have been the subject of research in recent years. However, most of the studies have presented preliminary in vitro results that can significantly differ under in vivo settings. Here, we focus on the studies conducted with animal models to reveal the current status of micro/nanorobotic applications in real-world conditions. By a categorization based on target locations, we highlight the main strategies employed in organs and other body parts. We also discuss key challenges that require interest before the successful translation of micro/nanorobots to the clinic.
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Affiliation(s)
- Cagatay M Oral
- Future Energy and Innovation Laboratory, Central European Institute of Technology, Brno University of Technology, Purkynova 123, 61200, Brno, Czech Republic.
| | - Martin Pumera
- Future Energy and Innovation Laboratory, Central European Institute of Technology, Brno University of Technology, Purkynova 123, 61200, Brno, Czech Republic.
- Faculty of Electrical Engineering and Computer Science, VSB - Technical University of Ostrava, 17. Listopadu 2172/15, 70800, Ostrava, Czech Republic
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Yu L, Yang M, Guan J, Mou F. Ultrasmall Fe 2O 3 Tubular Nanomotors: The First Example of Swarming Photocatalytic Nanomotors Operating in High-Electrolyte Media. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:1370. [PMID: 37110955 PMCID: PMC10143400 DOI: 10.3390/nano13081370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/11/2023] [Accepted: 04/12/2023] [Indexed: 06/19/2023]
Abstract
Self-propelled chemical micro/nanomotors (MNMs) have demonstrated considerable potential in targeted drug delivery, (bio)sensing, and environmental remediation due to their autonomous nature and possible intelligent self-targeting behaviors (e.g., chemotaxis and phototaxis). However, these MNMs are commonly limited by their primary propulsion mechanisms of self-electrophoresis and electrolyte self-diffusiophoresis, making them prone to quenching in high electrolyte environments. Thus, the swarming behaviors of chemical MNMs in high-electrolyte media remain underexplored, despite their potential to enable the execution of complex tasks in high-electrolyte biological media or natural waters. In this study, we develop ultrasmall tubular nanomotors that exhibit ion-tolerant propulsions and collective behaviors. Upon vertical upward UV irradiation, the ultrasmall Fe2O3 tubular nanomotors (Fe2O3 TNMs) demonstrate positive superdiffusive photogravitaxis and can further self-organize into nanoclusters near the substrate in a reversible manner. After self-organization, the Fe2O3 TNMs exhibit a pronounced emergent behavior, allowing them to switch from random superdiffusions to ballistic motions near the substrate. Even at a high electrolyte concentration (Ce), the ultrasmall Fe2O3 TNMs retain a relatively thick electrical double layer (EDL) compared to their size, and the electroosmotic slip flow in their EDL is strong enough to propel them and induce phoretic interactions among them. As a result, the nanomotors can rapidly concentrate near the substrate and then gather into motile nanoclusters in high-electrolyte environments. This work opens a gate for designing swarming ion-tolerant chemical nanomotors and may expedite their applications in biomedicine and environmental remediation.
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Zhang H, Paik J. Lattice-and-Plate Model: Mechanics Modeling of Physical Origami Robots. Soft Robot 2023; 10:149-158. [PMID: 35714351 DOI: 10.1089/soro.2021.0172] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Origami robots are characterized by their compact design, quasi-two-dimensional manufacturing process, and folding joint-based transmission kinematics. The physical requirements in terms of payload, range of motion, and embedding core robotic components have made it unrealistic to rely on conventional mathematical models for designing these new robots. Therefore, origami robots require a comprehensive approach to model their mechanics. Currently, there is no generalized mechanics model to achieve this goal. Therefore, in this work, we propose a nonlinear lattice-and-plate model to simulate the mechanics of physical origami robots within several seconds, including the localized bending on flexible hinges, global displacements of rigid panels, and trajectory of predefined outputs. Moreover, this proposed model captures the large displacement and self-contact of adjacent panels during locomotion. We validate the efficiency of the model on various origami actuators, grippers, and metamaterials. To conclude, the computational model can help to accelerate the design iteration of origami robots.
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Affiliation(s)
- Hongying Zhang
- Department of Mechanical Engineering, National University of Singapore, Singapore, Singapore
| | - Jamie Paik
- Reconfigurable Robotics Laboratory, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
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Medical micro- and nanomotors in the body. Acta Pharm Sin B 2023; 13:517-541. [PMID: 36873176 PMCID: PMC9979267 DOI: 10.1016/j.apsb.2022.10.010] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 08/24/2022] [Accepted: 09/14/2022] [Indexed: 11/20/2022] Open
Abstract
Attributed to the miniaturized body size and active mobility, micro- and nanomotors (MNMs) have demonstrated tremendous potential for medical applications. However, from bench to bedside, massive efforts are needed to address critical issues, such as cost-effective fabrication, on-demand integration of multiple functions, biocompatibility, biodegradability, controlled propulsion and in vivo navigation. Herein, we summarize the advances of biomedical MNMs reported in the past two decades, with particular emphasis on the design, fabrication, propulsion, navigation, and the abilities of biological barriers penetration, biosensing, diagnosis, minimally invasive surgery and targeted cargo delivery. Future perspectives and challenges are discussed as well. This review can lay the foundation for the future direction of medical MNMs, pushing one step forward on the road to achieving practical theranostics using MNMs.
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Liang H, Peng F, Tu Y. Active therapy based on the byproducts of micro/nanomotors. NANOSCALE 2023; 15:953-962. [PMID: 36537366 DOI: 10.1039/d2nr05818a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Different from traditional colloidal particles based on Brownian motion, micro/nanomotors are micro/nanoscale devices capable of performing complex tasks in liquid media via transforming various energy sources into mechanical motion or actuation. Such unique self-propulsion endows motors with fantastic capabilities to access and enter the deep layer of targeted diseased tissue, which in turn breaks through the limitation of the poor permeability of traditional pharmaceutical preparations, thus providing giant prospects for active therapy. It is noteworthy that recently several studies, which utilized the byproducts generated in situ by micro/nanomotors to achieve active therapy, in a truly green zero-waste manner, have been carried out. In this minireview, we highlight the recent efforts with respect to active therapy based on the byproducts of micro/nanomotors, expecting to motivate readers to expand the practical biomedical application scope of micro/nanomotors in a broader horizon. Accompanied by ever booming enthusiasm and persevering exploration, micro/nanomotors are on their way to revolutionize conventional fields.
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Affiliation(s)
- Haiying Liang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
| | - Fei Peng
- School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China
| | - Yingfeng Tu
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
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Wang Y, Shen J, Handschuh-Wang S, Qiu M, Du S, Wang B. Microrobots for Targeted Delivery and Therapy in Digestive System. ACS NANO 2023; 17:27-50. [PMID: 36534488 DOI: 10.1021/acsnano.2c04716] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Untethered miniature robots enable targeted delivery and therapy deep inside the gastrointestinal tract in a minimally invasive manner. By combining actuation systems and imaging tools, significant progress has been made toward the development of functional microrobots. These robots can be actuated by external fields and fuels while featuring real-time tracking feedback toward certain regions and can perform the therapeutic process by rational exertion of the local environment of the gastrointestinal tract (e.g., pH, enzyme). Compared with conventional surgical tools, such as endoscopic devices and catheters, miniature robots feature minimally invasive diagnosis and treatment, multifunctionality, high safety and adaptivity, embodied intelligence, and easy access to tortuous and narrow lumens. In addition, the active motion of microrobots enhances local penetration and retention of drugs in tissues compared to common passive oral drug delivery. Based on the dissimilar microenvironments in the various sections of the gastrointestinal tract, this review introduces the advances of miniature robots for minimally invasive targeted delivery and therapy of diseases along the gastrointestinal tract. The imaging modalities for the tracking and their application scenarios are also discussed. We finally evaluate the challenges and barriers that retard their applications and hint on future research directions in this field.
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Affiliation(s)
- Yun Wang
- College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen518055, P.R. China
| | - Jie Shen
- Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen518036, P.R. China
| | - Stephan Handschuh-Wang
- College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen518055, P.R. China
| | - Ming Qiu
- Department of Neurosurgery, South China Hospital of Shenzhen University, Shenzhen518111, P.R. China
| | - Shiwei Du
- Department of Neurosurgery, South China Hospital of Shenzhen University, Shenzhen518111, P.R. China
| | - Ben Wang
- College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen518055, P.R. China
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Zhang D, Gorochowski TE, Marucci L, Lee HT, Gil B, Li B, Hauert S, Yeatman E. Advanced medical micro-robotics for early diagnosis and therapeutic interventions. Front Robot AI 2023; 9:1086043. [PMID: 36704240 PMCID: PMC9871318 DOI: 10.3389/frobt.2022.1086043] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 12/15/2022] [Indexed: 01/12/2023] Open
Abstract
Recent technological advances in micro-robotics have demonstrated their immense potential for biomedical applications. Emerging micro-robots have versatile sensing systems, flexible locomotion and dexterous manipulation capabilities that can significantly contribute to the healthcare system. Despite the appreciated and tangible benefits of medical micro-robotics, many challenges still remain. Here, we review the major challenges, current trends and significant achievements for developing versatile and intelligent micro-robotics with a focus on applications in early diagnosis and therapeutic interventions. We also consider some recent emerging micro-robotic technologies that employ synthetic biology to support a new generation of living micro-robots. We expect to inspire future development of micro-robots toward clinical translation by identifying the roadblocks that need to be overcome.
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Affiliation(s)
- Dandan Zhang
- Department of Engineering Mathematics, University of Bristol, Bristol, United Kingdom
- Bristol Robotics Laboratory, Bristol, United Kingdom
| | - Thomas E. Gorochowski
- School of Biological Sciences, University of Bristol, Bristol, United Kingdom
- BrisEngBio, University of Bristol, Bristol, United Kingdom
| | - Lucia Marucci
- Department of Engineering Mathematics, University of Bristol, Bristol, United Kingdom
- School of Biological Sciences, University of Bristol, Bristol, United Kingdom
- BrisEngBio, University of Bristol, Bristol, United Kingdom
| | - Hyun-Taek Lee
- Department of Mechanical Engineering, Inha University, Incheon, South Korea
| | - Bruno Gil
- Department of Electrical and Electronic Engineering, Imperial College London, London, United Kingdom
| | - Bing Li
- The Institute for Materials Discovery, University College London, London, United Kingdom
- Department of Brain Science, Imperial College London, London, United Kingdom
- Care Research & Technology Centre, UK Dementia Research Institute, Imperial College London, London, United Kingdom
| | - Sabine Hauert
- Department of Engineering Mathematics, University of Bristol, Bristol, United Kingdom
- Bristol Robotics Laboratory, Bristol, United Kingdom
- BrisEngBio, University of Bristol, Bristol, United Kingdom
| | - Eric Yeatman
- Department of Electrical and Electronic Engineering, Imperial College London, London, United Kingdom
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30
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Manero A, Crawford KE, Prock‐Gibbs H, Shah N, Gandhi D, Coathup MJ. Improving disease prevention, diagnosis, and treatment using novel bionic technologies. Bioeng Transl Med 2023; 8:e10359. [PMID: 36684104 PMCID: PMC9842045 DOI: 10.1002/btm2.10359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 05/09/2022] [Accepted: 05/30/2022] [Indexed: 01/25/2023] Open
Abstract
Increased human life expectancy, due in part to improvements in infant and childhood survival, more active lifestyles, in combination with higher patient expectations for better health outcomes, is leading to an extensive change in the number, type and manner in which health conditions are treated. Over the next decades as the global population rapidly progresses toward a super-aging society, meeting the long-term quality of care needs is forecast to present a major healthcare challenge. The goal is to ensure longer periods of good health, a sustained sense of well-being, with extended periods of activity, social engagement, and productivity. To accomplish these goals, multifunctionalized interfaces are an indispensable component of next generation medical technologies. The development of more sophisticated materials and devices as well as an improved understanding of human disease is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer's disease and will impact disease prevention. This review examines emerging cutting-edge bionic materials, devices and technologies developed to advance disease prevention, and medical care and treatment in our elderly population including developments in smart bandages, cochlear implants, and the increasing role of artificial intelligence and nanorobotics in medicine.
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Affiliation(s)
- Albert Manero
- Limbitless SolutionsUniversity of Central FloridaOrlandoFloridaUSA
- Biionix ClusterUniversity of Central FloridaOrlandoFloridaUSA
| | - Kaitlyn E. Crawford
- Biionix ClusterUniversity of Central FloridaOrlandoFloridaUSA
- Department of Materials Science and EngineeringUniversity of Central FloridaOrlandoFloridaUSA
| | | | - Neel Shah
- College of MedicineUniversity of Central FloridaOrlandoFloridaUSA
| | - Deep Gandhi
- College of MedicineUniversity of Central FloridaOrlandoFloridaUSA
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Wang J, Dong Y, Ma P, Wang Y, Zhang F, Cai B, Chen P, Liu BF. Intelligent Micro-/Nanorobots for Cancer Theragnostic. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2201051. [PMID: 35385160 DOI: 10.1002/adma.202201051] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/15/2022] [Indexed: 06/14/2023]
Abstract
Cancer is one of the most intractable diseases owing to its high mortality rate and lack of effective diagnostic and treatment tools. Advancements in micro-/nanorobot (MNR)-assisted sensing, imaging, and therapeutics offer unprecedented opportunities to develop MNR-based cancer theragnostic platforms. Unlike ordinary nanoparticles, which exhibit Brownian motion in biofluids, MNRs overcome viscous resistance in an ultralow Reynolds number (Re << 1) environment by effective self-propulsion. This unique locomotion property has motivated the advanced design and functionalization of MNRs as a basis for next-generation cancer-therapy platforms, which offer the potential for precise distribution and improved permeation of therapeutic agents. Enhanced barrier penetration, imaging-guided operation, and biosensing are additionally studied to enable the promising cancer-related applications of MNRs. Herein, the recent advances in MNR-based cancer therapy are comprehensively addresses, including actuation engines, diagnostics, medical imaging, and targeted drug delivery; promising research opportunities that can have a profound impact on cancer therapy over the next decade is highlighted.
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Affiliation(s)
- Jie Wang
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
| | - Yue Dong
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
| | - Peng Ma
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
| | - Yu Wang
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
| | - Fangyu Zhang
- Department of Nano Engineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Bocheng Cai
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, 94720, USA
| | - Peng Chen
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
| | - Bi-Feng Liu
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
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32
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King JB, Katta N, Parekh SH, Milner TE, Tunnell JW. Tissue harvest with a laser microbiopsy. JOURNAL OF BIOMEDICAL OPTICS 2022; 27:125001. [PMID: 36530344 PMCID: PMC9749420 DOI: 10.1117/1.jbo.27.12.125001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 11/22/2022] [Indexed: 06/17/2023]
Abstract
Significance Traditional pathology workflow suffers from limitations including biopsy invasiveness, small fraction of large tissue samples being analyzed, and complex and time-consuming processing. Aim We address limitations of conventional pathology workflow through development of a laser microbiopsy device for minimally invasive harvest of sub-microliter tissue volumes. Laser microbiopsy combined with rapid diagnostic methods, such as virtual hematoxylin and eosin (H&E) imaging has potential to provide rapid minimally invasive tissue diagnosis. Approach Laser microbiopsies were harvested using an annular shaped Ho:YAG laser beam focused onto the tissue surface. As the annulus was ablated, the tissue section in the center of the annulus was ejected and collected directly onto a glass slide for analysis. Cryogen spray cooling was used before and after laser harvest to limit thermal damage. Microbiopsies were collected from porcine skin and kidney. Harvested microbiopsies were imaged with confocal microscopy and digitally false colored to provide virtual H&E images. Results Microbiopsies were successfully harvested from porcine skin and kidney. Computational and experimental results show the benefit of cryogen pre- and post-cooling to limit thermal damage. Virtual H&E images of microbiopsies retained observable cellular features including cell nuclei. Conclusions Laser microbiopsy with virtual H&E imaging shows promise as a potential rapid and minimally invasive tool for biopsy and diagnosis.
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Affiliation(s)
- Jason B. King
- The University of Texas at Austin, Department of Biomedical Engineering, Austin, Texas, United States
| | - Nitesh Katta
- University of California Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - Sapun H. Parekh
- The University of Texas at Austin, Department of Biomedical Engineering, Austin, Texas, United States
| | - Thomas E. Milner
- University of California Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States
| | - James W. Tunnell
- The University of Texas at Austin, Department of Biomedical Engineering, Austin, Texas, United States
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Ghosh A, Liu W, Li L, Pahapale GJ, Choi SY, Xu L, Huang Q, Zhang R, Zhong Z, Selaru FM, Gracias DH. Autonomous Untethered Microinjectors for Gastrointestinal Delivery of Insulin. ACS NANO 2022; 16:16211-16220. [PMID: 36201302 PMCID: PMC9960177 DOI: 10.1021/acsnano.2c05098] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
The delivery of macromolecular drugs via the gastrointestinal (GI) tract is challenging as these drugs display low stability as well as poor absorption across the intestinal epithelium. While permeation-enhancing drug delivery methods can increase the bioavailability of low molecular weight drugs, the effective delivery of high molecular weight drugs across the tight epithelial cell junctions remains a formidable challenge. Here, we describe autonomous microinjectors that are deployed in the GI tract, then efficiently penetrate the GI mucosa to deliver a macromolecular drug, insulin, to the systemic circulation. We performed in vitro studies to characterize insulin release and assess the penetration capability of microinjectors and we measured the in vivo release of insulin in live rats. We found that the microinjectors administered within the luminal GI tract could deliver insulin transmucosally to the systemic circulation at levels similar to those with intravenously administered insulin. Due to their small size, tunability in sizing and dosing, wafer-scale fabrication, and parallel, autonomous operation, we anticipate that these microinjectors will significantly advance drug delivery across the GI tract mucosa to the systemic circulation in a safe manner.
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Affiliation(s)
- Arijit Ghosh
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Wangqu Liu
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Ling Li
- Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Gayatri J. Pahapale
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Si Young Choi
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Liyi Xu
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Qi Huang
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Ruili Zhang
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Zijian Zhong
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Florin M. Selaru
- Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - David H. Gracias
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
- Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Center for Microphysiological Systems, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA
- Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
- Laboratory for Computational Sensing and Robotics (LCSR), Johns Hopkins University, Baltimore, MD 21218, USA
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Mukherjee P, Park SH, Pathak N, Patino CA, Bao G, Espinosa HD. Integrating Micro and Nano Technologies for Cell Engineering and Analysis: Toward the Next Generation of Cell Therapy Workflows. ACS NANO 2022; 16:15653-15680. [PMID: 36154011 DOI: 10.1021/acsnano.2c05494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
The emerging field of cell therapy offers the potential to treat and even cure a diverse array of diseases for which existing interventions are inadequate. Recent advances in micro and nanotechnology have added a multitude of single cell analysis methods to our research repertoire. At the same time, techniques have been developed for the precise engineering and manipulation of cells. Together, these methods have aided the understanding of disease pathophysiology, helped formulate corrective interventions at the cellular level, and expanded the spectrum of available cell therapeutic options. This review discusses how micro and nanotechnology have catalyzed the development of cell sorting, cellular engineering, and single cell analysis technologies, which have become essential workflow components in developing cell-based therapeutics. The review focuses on the technologies adopted in research studies and explores the opportunities and challenges in combining the various elements of cell engineering and single cell analysis into the next generation of integrated and automated platforms that can accelerate preclinical studies and translational research.
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Affiliation(s)
- Prithvijit Mukherjee
- Department of Mechanical Engineering, Northwestern University, Evanston, Illinois 60208, United States
- Theoretical and Applied Mechanics Program, Northwestern University, Evanston, Illinois 60208, United States
| | - So Hyun Park
- Department of Bioengineering, Rice University, 6500 Main Street, Houston, Texas 77030, United States
| | - Nibir Pathak
- Department of Mechanical Engineering, Northwestern University, Evanston, Illinois 60208, United States
- Theoretical and Applied Mechanics Program, Northwestern University, Evanston, Illinois 60208, United States
| | - Cesar A Patino
- Department of Mechanical Engineering, Northwestern University, Evanston, Illinois 60208, United States
| | - Gang Bao
- Department of Bioengineering, Rice University, 6500 Main Street, Houston, Texas 77030, United States
| | - Horacio D Espinosa
- Department of Mechanical Engineering, Northwestern University, Evanston, Illinois 60208, United States
- Theoretical and Applied Mechanics Program, Northwestern University, Evanston, Illinois 60208, United States
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Son H, Park Y, Na Y, Yoon C. 4D Multiscale Origami Soft Robots: A Review. Polymers (Basel) 2022; 14:polym14194235. [PMID: 36236182 PMCID: PMC9571758 DOI: 10.3390/polym14194235] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/29/2022] [Accepted: 10/06/2022] [Indexed: 11/06/2022] Open
Abstract
Time-dependent shape-transferable soft robots are important for various intelligent applications in flexible electronics and bionics. Four-dimensional (4D) shape changes can offer versatile functional advantages during operations to soft robots that respond to external environmental stimuli, including heat, pH, light, electric, or pneumatic triggers. This review investigates the current advances in multiscale soft robots that can display 4D shape transformations. This review first focuses on material selection to demonstrate 4D origami-driven shape transformations. Second, this review investigates versatile fabrication strategies to form the 4D mechanical structures of soft robots. Third, this review surveys the folding, rolling, bending, and wrinkling mechanisms of soft robots during operation. Fourth, this review highlights the diverse applications of 4D origami-driven soft robots in actuators, sensors, and bionics. Finally, perspectives on future directions and challenges in the development of intelligent soft robots in real operational environments are discussed.
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Affiliation(s)
- Hyegyo Son
- Department of Mechanical Systems Engineering, Sookmyung Women’s University, Seoul 04310, Korea
| | - Yunha Park
- Department of Mechanical Systems Engineering, Sookmyung Women’s University, Seoul 04310, Korea
| | - Youngjin Na
- Department of Mechanical Systems Engineering, Sookmyung Women’s University, Seoul 04310, Korea
- Correspondence: (Y.N.); (C.Y.)
| | - ChangKyu Yoon
- Department of Mechanical Systems Engineering, Sookmyung Women’s University, Seoul 04310, Korea
- Institute of Advanced Materials and Systems, Sookmyung Women’s University, Seoul 04310, Korea
- Correspondence: (Y.N.); (C.Y.)
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Zhou H, Dong G, Gao G, Du R, Tang X, Ma Y, Li J. Hydrogel-Based Stimuli-Responsive Micromotors for Biomedicine. CYBORG AND BIONIC SYSTEMS 2022; 2022:9852853. [PMID: 36285306 PMCID: PMC9579945 DOI: 10.34133/2022/9852853] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 09/23/2022] [Indexed: 11/07/2022] Open
Abstract
The rapid development of medical micromotors draws a beautiful blueprint for the noninvasive or minimally invasive diagnosis and therapy. By combining stimuli-sensitive hydrogel materials, micromotors are bestowed with new characteristics such as stimuli-responsive shape transformation/morphing, excellent biocompatibility and biodegradability, and drug loading ability. Actuated by chemical fuels or external fields (e.g., magnetic field, ultrasound, light, and electric field), hydrogel-based stimuli-responsive (HBSR) micromotors can be utilized to load therapeutic agents into the hydrogel networks or directly grip the target cargos (e.g., drug-loaded particles, cells, and thrombus), transport them to sites of interest (e.g., tumor area and diseased tissues), and unload the cargos or execute a specific task (e.g., cell capture, targeted sampling, and removal of blood clots) in response to a stimulus (e.g., change of temperature, pH, ion strength, and chemicals) in the physiological environment. The high flexibility, adaptive capacity, and shape morphing property enable the HBSR micromotors to complete specific medical tasks in complex physiological scenarios, especially in confined, hard-to-reach tissues, and vessels of the body. Herein, this review summarizes the current progress in hydrogel-based medical micromotors with stimuli responsiveness. The thermo-responsive, photothermal-responsive, magnetocaloric-responsive, pH-responsive, ionic-strength-responsive, and chemoresponsive micromotors are discussed in detail. Finally, current challenges and future perspectives for the development of HBSR micromotors in the biomedical field are discussed.
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Affiliation(s)
- Huaijuan Zhou
- Advanced Research Institute of Multidisciplinary Sciences, Beijing Institute of Technology, Beijing 100081, China
| | - Guozhao Dong
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China
| | - Ge Gao
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China
| | - Ran Du
- School of Materials Science & Engineering, Key Laboratory of High Energy Density Materials of the Ministry of Education, Beijing Institute of Technology, Beijing 100081, China
| | - Xiaoying Tang
- School of Life Science, Beijing Institute of Technology, Beijing 100081, China
| | - Yining Ma
- Department of Forensic Science, Jiangsu Police Institute, Nanjing 210031, China
| | - Jinhua Li
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China
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37
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Zhang Z, Wang Y, Wang Q, Shang L. Smart Film Actuators for Biomedical Applications. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2105116. [PMID: 35038215 DOI: 10.1002/smll.202105116] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 11/23/2021] [Indexed: 06/14/2023]
Abstract
Taking inspiration from the extremely flexible motion abilities in natural organisms, soft actuators have emerged in the past few decades. Particularly, smart film actuators (SFAs) demonstrate unique superiority in easy fabrication, tailorable geometric configurations, and programmable 3D deformations. Thus, they are promising in many biomedical applications, such as soft robotics, tissue engineering, delivery system, and organ-on-a-chip. In this review, the latest achievements of SFAs applied in biomedical fields are summarized. The authors start by introducing the fabrication techniques of SFAs, then shift to the topology design of SFAs, followed by their material selections and distinct actuating mechanisms. After that, their biomedical applications are categorized in practical aspects. The challenges and prospects of this field are finally discussed. The authors believe that this review can boost the development of soft robotics, biomimetics, and human healthcare.
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Affiliation(s)
- Zhuohao Zhang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Yu Wang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Qiao Wang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Luoran Shang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
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38
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Dunn CR, Lee BP, Rajachar RM. Thermomagnetic-Responsive Self-Folding Microgrippers for Improving Minimally Invasive Surgical Techniques and Biopsies. Molecules 2022; 27:5196. [PMID: 36014435 PMCID: PMC9412701 DOI: 10.3390/molecules27165196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/05/2022] [Accepted: 08/09/2022] [Indexed: 11/16/2022] Open
Abstract
Traditional open surgery complications are typically due to trauma caused by accessing the procedural site rather than the procedure itself. Minimally invasive surgery allows for fewer complications as microdevices operate through small incisions or natural orifices. However, current minimally invasive tools typically have restricted maneuverability, accessibility, and positional control of microdevices. Thermomagnetic-responsive microgrippers are microscopic multi-fingered devices that respond to temperature changes due to the presence of thermal-responsive polymers. Polymeric devices, made of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) and polypropylene fumarate (PPF), self-fold due to swelling and contracting of the hydrogel layer. In comparison, soft metallic devices feature a pre-stressed metal bilayer and polymer hinges that soften with increased temperature. Both types of microdevices can self-actuate when exposed to the elevated temperature of a cancerous tumor region, allowing for direct targeting for biopsies. Microgrippers can also be doped to become magnetically responsive, allowing for direction without tethers and the retrieval of microdevices containing excised tissue. The smaller size of stimuli-responsive microgrippers allows for their movement through hard-to-reach areas within the body and the successful extraction of intact cells, RNA and DNA. This review discusses the mechanisms of thermal- and magnetic-responsive microdevices and recent advances in microgripper technology to improve minimally invasive surgical techniques.
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Affiliation(s)
- Caleigh R. Dunn
- Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931, USA
| | - Bruce P. Lee
- Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931, USA
| | - Rupak M. Rajachar
- Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931, USA
- Marine Ecology and Telemetry Research (MarEcoTel), Seabeck, WA 98380, USA
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Guo K, Huang C, Miao Y, Cosgrove DJ, Hsia KJ. Leaf morphogenesis: The multifaceted roles of mechanics. MOLECULAR PLANT 2022; 15:1098-1119. [PMID: 35662674 DOI: 10.1016/j.molp.2022.05.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/18/2022] [Accepted: 05/26/2022] [Indexed: 05/12/2023]
Abstract
Plants produce a rich diversity of biological forms, and the diversity of leaves is especially notable. Mechanisms of leaf morphogenesis have been studied in the past two decades, with a growing focus on the interactive roles of mechanics in recent years. Growth of plant organs involves feedback by mechanical stress: growth induces stress, and stress affects growth and morphogenesis. Although much attention has been given to potential stress-sensing mechanisms and cellular responses, the mechanical principles guiding morphogenesis have not been well understood. Here we synthesize the overarching roles of mechanics and mechanical stress in multilevel and multiple stages of leaf morphogenesis, encompassing leaf primordium initiation, phyllotaxis and venation patterning, and the establishment of complex mature leaf shapes. Moreover, the roles of mechanics at multiscale levels, from subcellular cytoskeletal molecules to single cells to tissues at the organ scale, are articulated. By highlighting the role of mechanical buckling in the formation of three-dimensional leaf shapes, this review integrates the perspectives of mechanics and biology to provide broader insights into the mechanobiology of leaf morphogenesis.
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Affiliation(s)
- Kexin Guo
- School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore
| | - Changjin Huang
- School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore
| | - Yansong Miao
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
| | - Daniel J Cosgrove
- Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA.
| | - K Jimmy Hsia
- School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
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40
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Agarwal D, Thakur AD, Thakur A. Magnetic microbot-based micromanipulation of surrogate biological objects in fluidic channels. JOURNAL OF MICRO-BIO ROBOTICS 2022. [DOI: 10.1007/s12213-022-00151-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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41
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Ze Q, Wu S, Dai J, Leanza S, Ikeda G, Yang PC, Iaccarino G, Zhao RR. Spinning-enabled wireless amphibious origami millirobot. Nat Commun 2022; 13:3118. [PMID: 35701405 PMCID: PMC9198078 DOI: 10.1038/s41467-022-30802-w] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/19/2022] [Indexed: 12/22/2022] Open
Abstract
Wireless millimeter-scale origami robots have recently been explored with great potential for biomedical applications. Existing millimeter-scale origami devices usually require separate geometrical components for locomotion and functions. Additionally, none of them can achieve both on-ground and in-water locomotion. Here we report a magnetically actuated amphibious origami millirobot that integrates capabilities of spinning-enabled multimodal locomotion, delivery of liquid medicine, and cargo transportation with wireless operation. This millirobot takes full advantage of the geometrical features and folding/unfolding capability of Kresling origami, a triangulated hollow cylinder, to fulfill multifunction: its geometrical features are exploited for generating omnidirectional locomotion in various working environments through rolling, flipping, and spinning-induced propulsion; the folding/unfolding is utilized as a pumping mechanism for controlled delivery of liquid medicine; furthermore, the spinning motion provides a sucking mechanism for targeted solid cargo transportation. We anticipate the amphibious origami millirobots can potentially serve as minimally invasive devices for biomedical diagnoses and treatments. Wireless millirobots are promising as minimally invasive biomedical devices. Here, the authors design a magnetically actuated amphibious millirobot that integrates spinning-enabled locomotion, targeted drug delivery, and cargo transportation by utilizing geometrical features and folding/unfolding capability of the Kresling origami.
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Affiliation(s)
- Qiji Ze
- Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA
| | - Shuai Wu
- Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA
| | - Jize Dai
- Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA
| | - Sophie Leanza
- Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA
| | - Gentaro Ikeda
- Stanford Cardiovascular Institute and Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Phillip C Yang
- Stanford Cardiovascular Institute and Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Gianluca Iaccarino
- Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA.,Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA, 94305, USA
| | - Ruike Renee Zhao
- Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA.
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42
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Zhang X, Wu Y, Li Y, Jiang H, Yang Q, Wang Z, Liu J, Wang Y, Fan X, Kong J. Small-scale soft grippers with environmentally responsive logic gates. MATERIALS HORIZONS 2022; 9:1431-1439. [PMID: 35380150 DOI: 10.1039/d2mh00097k] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Small-scale soft grippers are adaptive and deformable, and can be utilized for confined environments (e.g., the human body). Small-scale soft grippers require logic-based computation to achieve intelligent control and perform logical analysis of the surrounding information. However, it is a great challenge to integrate electronic chips and power supplies (i.e., batteries) on their small systems. Here, the approach provides a route to add computational capabilities via environmentally responsive logic gates in small-scale soft grippers, without electronics, external control, or tethering. Various origami-inspired grippers performing YES, NOT, XOR, AND, OR, NOR and NAND gates, respectively, were developed by stimuli-responsive hydrogels as building blocks. Although the hydrogels respond to different kinds of stimuli, their outputs are the same: a change in hydrogel size, leading to the bending of the arms of the grippers. Hence, the logic gates can be integrated easily within a gripper (e.g., connecting an AND gate to another AND gate). Moreover, the gripper fabricated by dual-responsive hydrogels can intelligently and autonomously switch from an AND gate to an OR gate upon varied environmental stimuli. In addition, a magnetic gripper with an AND gate was fabricated that can analyse different stimuli, and capture and release the targeted object via the environmentally responsive logic gates. This strategy provides a new route to incorporate on-board perception, control and computation via environmentally responsive logic gates in small-scale soft robots and machines.
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Affiliation(s)
- Xuan Zhang
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - Ya Wu
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - Yan Li
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - He Jiang
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - Qinglin Yang
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - Zichao Wang
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - Jiahao Liu
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - Yang Wang
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - Xiaodong Fan
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
| | - Jie Kong
- MOE Key Laboratory of Materials Physics and Chemistry in Extraordinary Conditions, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
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43
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Wang Z, Xu Z, Zhu B, Zhang Y, Lin J, Wu Y, Wu D. Design, fabrication and application of magnetically actuated micro/nanorobots: a review. NANOTECHNOLOGY 2022; 33:152001. [PMID: 34915458 DOI: 10.1088/1361-6528/ac43e6] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 12/16/2021] [Indexed: 06/14/2023]
Abstract
Magnetically actuated micro/nanorobots are typical micro- and nanoscale artificial devices with favorable attributes of quick response, remote and contactless control, harmless human-machine interaction and high economic efficiency. Under external magnetic actuation strategies, they are capable of achieving elaborate manipulation and navigation in extreme biomedical environments. This review focuses on state-of-the-art progresses in design strategies, fabrication techniques and applications of magnetically actuated micro/nanorobots. Firstly, recent advances of various robot designs, including helical robots, surface walkers, ciliary robots, scaffold robots and biohybrid robots, are discussed separately. Secondly, the main progresses of common fabrication techniques are respectively introduced, and application achievements on these robots in targeted drug delivery, minimally invasive surgery and cell manipulation are also presented. Finally, a short summary is made, and the current challenges and future work for magnetically actuated micro/nanorobots are discussed.
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Affiliation(s)
- Zhongbao Wang
- Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China
- Shenzhen Research Institute of Xiamen University, Shenzhen, 518057, People's Republic of China
| | - Zhenjin Xu
- Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China
- Shenzhen Research Institute of Xiamen University, Shenzhen, 518057, People's Republic of China
| | - Bin Zhu
- Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China
- Shenzhen Research Institute of Xiamen University, Shenzhen, 518057, People's Republic of China
| | - Yang Zhang
- Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China
- Shenzhen Research Institute of Xiamen University, Shenzhen, 518057, People's Republic of China
| | - Jiawei Lin
- Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China
- Shenzhen Research Institute of Xiamen University, Shenzhen, 518057, People's Republic of China
| | - Yigen Wu
- Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China
- Shenzhen Research Institute of Xiamen University, Shenzhen, 518057, People's Republic of China
| | - Dezhi Wu
- Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China
- Shenzhen Research Institute of Xiamen University, Shenzhen, 518057, People's Republic of China
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44
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Tanjeem N, Minnis MB, Hayward RC, Shields CW. Shape-Changing Particles: From Materials Design and Mechanisms to Implementation. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2105758. [PMID: 34741359 PMCID: PMC9579005 DOI: 10.1002/adma.202105758] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/06/2021] [Indexed: 05/05/2023]
Abstract
Demands for next-generation soft and responsive materials have sparked recent interest in the development of shape-changing particles and particle assemblies. Over the last two decades, a variety of mechanisms that drive shape change have been explored and integrated into particulate systems. Through a combination of top-down fabrication and bottom-up synthesis techniques, shape-morphing capabilities extend from the microscale to the nanoscale. Consequently, shape-morphing particles are rapidly emerging in a variety of contexts, including photonics, microfluidics, microrobotics, and biomedicine. Herein, the key mechanisms and materials that facilitate shape changes of microscale and nanoscale particles are discussed. Recent progress in the applications made possible by these particles is summarized, and perspectives on their promise and key open challenges in the field are discussed.
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Affiliation(s)
- Nabila Tanjeem
- Department of Chemical & Biological Engineering, University of Colorado, Boulder, 3415 Colorado Avenue, Boulder, CO, 80303, USA
| | - Montana B Minnis
- Department of Chemical & Biological Engineering, University of Colorado, Boulder, 3415 Colorado Avenue, Boulder, CO, 80303, USA
| | - Ryan C Hayward
- Department of Chemical & Biological Engineering, University of Colorado, Boulder, 3415 Colorado Avenue, Boulder, CO, 80303, USA
| | - Charles Wyatt Shields
- Department of Chemical & Biological Engineering, University of Colorado, Boulder, 3415 Colorado Avenue, Boulder, CO, 80303, USA
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45
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Abstract
In contrast to conventional hard actuators, soft actuators offer many vivid advantages, such as improved flexibility, adaptability, and reconfigurability, which are intrinsic to living systems. These properties make them particularly promising for different applications, including soft electronics, surgery, drug delivery, artificial organs, or prosthesis. The additional degree of freedom for soft actuatoric devices can be provided through the use of intelligent materials, which are able to change their structure, macroscopic properties, and shape under the influence of external signals. The use of such intelligent materials allows a substantial reduction of a device's size, which enables a number of applications that cannot be realized by externally powered systems. This review aims to provide an overview of the properties of intelligent synthetic and living/natural materials used for the fabrication of soft robotic devices. We discuss basic physical/chemical properties of the main kinds of materials (elastomers, gels, shape memory polymers and gels, liquid crystalline elastomers, semicrystalline ferroelectric polymers, gels and hydrogels, other swelling polymers, materials with volume change during melting/crystallization, materials with tunable mechanical properties, and living and naturally derived materials), how they are related to actuation and soft robotic application, and effects of micro/macro structures on shape transformation, fabrication methods, and we highlight selected applications.
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Affiliation(s)
- Indra Apsite
- Faculty of Engineering Science, Department of Biofabrication, University of Bayreuth, Ludwig Thoma Str. 36A, 95447 Bayreuth, Germany
| | - Sahar Salehi
- Department of Biomaterials, Center of Energy Technology und Materials Science, University of Bayreuth, Prof.-Rüdiger-Bormann-Straße 1, 95447 Bayreuth, Germany
| | - Leonid Ionov
- Faculty of Engineering Science, Department of Biofabrication, University of Bayreuth, Ludwig Thoma Str. 36A, 95447 Bayreuth, Germany.,Bavarian Polymer Institute, University of Bayreuth, Universitätsstr. 30, 95440 Bayreuth, Germany
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46
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Going Hands-Free: MagnetoSuture™ for Untethered Guided Needle Penetration of Human Tissue Ex Vivo. ROBOTICS 2021. [DOI: 10.3390/robotics10040129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The application of force in surgical settings is typically accomplished via physical tethers to the surgical tool. While physical tethers are common and critical, some internal surgical procedures may benefit from a tetherless operation of needles, possibly reducing the number of ports in the patient or the amount of tissue damage caused by tools used to manipulate needles. Magnetic field gradients can dynamically apply kinetic forces to magnetizable objects free of such tethers, possibly enabling ultra-minimally invasive robotic surgical procedures. We demonstrate the untethered manipulation of a suture needle in vitro, exemplified by steering through narrow holes, as well as needle penetration through excised rat and human tissues. We present proof of principle manipulations for the fully untethered control of a minimally modified, standard stainless steel surgical suture needle.
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47
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A Review of Microrobot's System: Towards System Integration for Autonomous Actuation In Vivo. MICROMACHINES 2021; 12:mi12101249. [PMID: 34683300 PMCID: PMC8540518 DOI: 10.3390/mi12101249] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 10/07/2021] [Accepted: 10/11/2021] [Indexed: 12/30/2022]
Abstract
Microrobots have received great attention due to their great potential in the biomedical field, and there has been extraordinary progress on them in many respects, making it possible to use them in vivo clinically. However, the most important question is how to get microrobots to a given position accurately. Therefore, autonomous actuation technology based on medical imaging has become the solution receiving the most attention considering its low precision and efficiency of manual control. This paper investigates key components of microrobot’s autonomous actuation systems, including actuation systems, medical imaging systems, and control systems, hoping to help realize system integration of them. The hardware integration has two situations according to sharing the transmitting equipment or not, with the consideration of interference, efficiency, microrobot’s material and structure. Furthermore, system integration of hybrid actuation and multimodal imaging can improve the navigation effect of the microrobot. The software integration needs to consider the characteristics and deficiencies of the existing actuation algorithms, imaging algorithms, and the complex 3D working environment in vivo. Additionally, considering the moving distance in the human body, the autonomous actuation system combined with rapid delivery methods can deliver microrobots to specify position rapidly and precisely.
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48
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Wan M, Liu Z, Li T, Chen H, Wang Q, Chen T, Tao Y, Mao C. Zwitterion-Based Hydrogen Sulfide Nanomotors Induce Multiple Acidosis in Tumor Cells by Destroying Tumor Metabolic Symbiosis. Angew Chem Int Ed Engl 2021; 60:16139-16148. [PMID: 33914416 DOI: 10.1002/anie.202104304] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Indexed: 12/17/2022]
Abstract
Destruction of tumor metabolism symbiosis is an attractive cancer treatment method which targets tumor cells with little harm to normal cells. Yet, a single intervention strategy and poor penetration of the drug in tumor tissue result in limited effect. Herein, we propose a zero-waste zwitterion-based hydrogen sulfide (H2 S)-driven nanomotor based on the basic principle of reaction in human body. When loaded with monocarboxylic acid transporter inhibitor α-cyano-4-hydroxycinnamic acid (α-CHCA), the nanomotor can move in tumor microenvironment and induce multiple acidosis of tumor cells and inhibit tumor growth through the synergistic effect of motion effect, driving force H2 S and α-CHCA. Given the good biosafety of the substrate and driving gas of this kind of nanomotor, as well as the limited variety of nanomotors currently available to move in the tumor microenvironment, this kind of nanomotor may provide a competitive candidate for the active drug delivery system of cancer treatment.
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Affiliation(s)
- Mimi Wan
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Zhiyong Liu
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Ting Li
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Huan Chen
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Qi Wang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Tiantian Chen
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Yingfang Tao
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
| | - Chun Mao
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China
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49
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Wan M, Liu Z, Li T, Chen H, Wang Q, Chen T, Tao Y, Mao C. Zwitterion‐Based Hydrogen Sulfide Nanomotors Induce Multiple Acidosis in Tumor Cells by Destroying Tumor Metabolic Symbiosis. Angew Chem Int Ed Engl 2021. [DOI: 10.1002/ange.202104304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Mimi Wan
- National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University Nanjing 210023 China
| | - Zhiyong Liu
- National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University Nanjing 210023 China
| | - Ting Li
- National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University Nanjing 210023 China
| | - Huan Chen
- National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University Nanjing 210023 China
| | - Qi Wang
- National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University Nanjing 210023 China
| | - Tiantian Chen
- National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University Nanjing 210023 China
| | - Yingfang Tao
- National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University Nanjing 210023 China
| | - Chun Mao
- National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University Nanjing 210023 China
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50
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Manamanchaiyaporn L, Tang X, Zheng Y, Yan X. Molecular Transport of a Magnetic Nanoparticle Swarm Towards Thrombolytic Therapy. IEEE Robot Autom Lett 2021. [DOI: 10.1109/lra.2021.3068978] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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