Biomedical Microdevices: Design, Fabrication and Application

A special issue of Micromachines (ISSN 2072-666X).

Deadline for manuscript submissions: closed (30 November 2017) | Viewed by 49323

Special Issue Editor


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Guest Editor
Department of Mechanical Engineering and McMaster School of Biomedical Engineering, McMaster University, Hamilton, ON L8S 4L7, Canada
Interests: micro/nanofabrication; bioprinting; biomedical microdevices; microelectromechanical systems; microfluidics; medical and environmental sensors; smart textiles; biomaterials; artificial organs
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Special Issue Information

Dear Colleagues,

Over the past 30 years, microfabrication technology has been applied to miniaturize biomedical devices. Key advantages of miniaturization include smaller size and weight, lower power consumption, portability, lower cost, and, in some cases, greater precision or faster analysis time. A large body of literature exists on these microdevices, which have been developed for diagnostics, drug delivery, drug discovery, microscale chemical production, tissue engineering, artificial organs and microimplants. A variety of design approaches, materials, fabrication methods and transduction techniques have been used in these devices.

In this special issue, we seek a collection of articles that describe the developments in this field, highlights key issues or challenges, and showcases recent work and emerging trends. They include review articles that synthesize and organize the research and development in these application areas as well as original research papers that present novel design concepts, fabrication methods or new areas of application of microdevices in the biology and medicine.  

Prof. P. Ravi Selvaganapathy
Guest Editor

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Keywords

  • Diagnostics
  • Drug delivery
  • Drug Discovery
  • Tissue Engineering
  • Bioprinting
  • Artificial Organs
  • Lab-on-Chip
  • Micropumps
  • Microvalves
  • Micromixers
  • Microfabrication
  • Microfluidics
  • Microreactors

Published Papers (8 papers)

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Research

18 pages, 4328 KiB  
Article
Study of the Operational Safety of a Vascular Interventional Surgical Robotic System
by Jian Guo, Xiaoliang Jin and Shuxiang Guo
Micromachines 2018, 9(3), 119; https://doi.org/10.3390/mi9030119 - 08 Mar 2018
Cited by 52 | Viewed by 5476
Abstract
This paper proposes an operation safety early warning system based on LabView (2014, National Instruments Corporation, Austin, TX, USA) for vascular interventional surgery (VIS) robotic system. The system not only provides intuitive visual feedback information for the surgeon, but also has a safety [...] Read more.
This paper proposes an operation safety early warning system based on LabView (2014, National Instruments Corporation, Austin, TX, USA) for vascular interventional surgery (VIS) robotic system. The system not only provides intuitive visual feedback information for the surgeon, but also has a safety early warning function. It is well known that blood vessels differ in their ability to withstand stress in different age groups, therefore, the operation safety early warning system based on LabView has a vascular safety threshold function that changes in real-time, which can be oriented to different age groups of patients and a broader applicable scope. In addition, the tracing performance of the slave manipulator to the master manipulator is also an important index for operation safety. Therefore, we also transformed the slave manipulator and integrated the displacement error compensation algorithm in order to improve the tracking ability of the slave manipulator to the master manipulator and reduce master–slave tracking errors. We performed experiments “in vitro” to validate the proposed system. According to previous studies, 0.12 N is the maximum force when the blood vessel wall has been penetrated. Experimental results showed that the proposed operation safety early warning system based on LabView combined with operating force feedback can effectively avoid excessive collisions between the surgical catheter and vessel wall to avoid vascular puncture. The force feedback error of the proposed system is maintained between ±20 mN, which is within the allowable safety range and meets our design requirements. Therefore, the proposed system can ensure the safety of surgery. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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23 pages, 9142 KiB  
Article
Analysis of PCR Kinetics inside a Microfluidic DNA Amplification System
by Jyh Jian Chen and Kun Tze Li
Micromachines 2018, 9(2), 48; https://doi.org/10.3390/mi9020048 - 28 Jan 2018
Cited by 20 | Viewed by 5800
Abstract
In order to analyze the DNA amplification numerically with integration of the DNA kinetics, three-dimensional simulations, including flow and thermal fields, and one-dimensional polymerase chain reaction (PCR) kinetics are presented. The simulated results are compared with experimental data that have been applied to [...] Read more.
In order to analyze the DNA amplification numerically with integration of the DNA kinetics, three-dimensional simulations, including flow and thermal fields, and one-dimensional polymerase chain reaction (PCR) kinetics are presented. The simulated results are compared with experimental data that have been applied to the operation of a continuous-flow PCR device. Microchannels fabricated by Micro Electro-Mechanical Systems (MEMS) technologies are shown. Comprehensive simulations of the flow and thermal fields and experiments measuring temperatures during thermal cycling are presented first. The resultant velocity and temperature profiles from the simulations are introduced to the mathematical models of PCR kinetics. Then kinetic equations are utilized to determine the evolution of the species concentrations inside the DNA mixture along the microchannel. The exponential growth of the double-stranded DNA concentration is investigated numerically with the various operational parameters during PCR. Next a 190-bp segment of Bartonella DNA is amplified to evaluate the PCR performance. The trends of the experimental results and numerical data regarding the DNA amplification are similar. The unique architecture built in this study can be applied to a low-cost portable PCR system in the future. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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15 pages, 11296 KiB  
Article
Design and Near-Infrared Actuation of a Gold Nanorod–Polymer Microelectromechanical Device for On-Demand Drug Delivery
by John Jackson, Aurora Chen, Hongbin Zhang, Helen Burt and Mu Chiao
Micromachines 2018, 9(1), 28; https://doi.org/10.3390/mi9010028 - 13 Jan 2018
Cited by 9 | Viewed by 5497
Abstract
Polymeric drug delivery systems usually deliver drugs by diffusion with an initial burst of release followed by a slower prolonged release phase. An optimal system would release exact doses of drugs using an on-demand external actuation system. The purpose of this study was [...] Read more.
Polymeric drug delivery systems usually deliver drugs by diffusion with an initial burst of release followed by a slower prolonged release phase. An optimal system would release exact doses of drugs using an on-demand external actuation system. The purpose of this study was to design and characterize a novel drug-delivery device that utilizes near infrared (NIR 800 nm) laser-actuated drug release. The device was constructed from biocompatible polymers comprising a reservoir of drug covered by an elastic perforated diaphragm composed of a bilayer of two polymers with different thermal expansion coefficients (ethylenevinylacetate (EVA) and polydimethylsiloxane (PDMS) containing gold nanoparticles). Upon illumination with a NIR laser, the gold nanoparticles rapidly heated the bilayer resulting in bending and a drug-pumping action through the perforated bilayer, following sequential laser-actuation cycles. Devices filled with the anti-proliferative drug docetaxel were seen to release only small amounts of drug by diffusion but to release large and reproducible amounts of drug over 20 s laser-actuation periods. Because NIR 800 nm is tissue-penetrating without heating tissue, suitable geometry drug-delivery devices might be implanted in the body to be actuated by an externally applied NIR laser to allow for on-demand exact drug dosing in vivo. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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6565 KiB  
Article
The Design, Fabrication, and Testing of an Electromagnetic Micropump with a Matrix-Patterned Magnetic Polymer Composite Actuator Membrane
by Muzalifah Mohd Said, Jumril Yunas, Badariah Bais, Azrul Azlan Hamzah and Burhanuddin Yeop Majlis
Micromachines 2018, 9(1), 13; https://doi.org/10.3390/mi9010013 - 31 Dec 2017
Cited by 36 | Viewed by 6926
Abstract
A valveless electromagnetic (EM) micropump with a matrix-patterned magnetic polymer composite actuator membrane structure was successfully designed and fabricated. The composite membrane structure is made of polydemethylsiloxane (PDMS) that is mixed with magnetic particles and patterned in matrix blocks. The matrix magnetic composite [...] Read more.
A valveless electromagnetic (EM) micropump with a matrix-patterned magnetic polymer composite actuator membrane structure was successfully designed and fabricated. The composite membrane structure is made of polydemethylsiloxane (PDMS) that is mixed with magnetic particles and patterned in matrix blocks. The matrix magnetic composite membrane was fabricated using a soft lithography process and expected to have a compact structure having sufficient magnetic force for membrane deformation and maintained membrane flexibility. The magnetic membrane was integrated with the microfluidic system and functionally tested. The experimental results show that a magnetic composite actuator membrane containing of 6% NdFeB is capable of producing a maximum membrane deflection up to 12.87 µm. The functionality test of the EM actuator for fluid pumping resulted in an extremely low sample injection flow rate of approximately 6.523 nL/min. It was also concluded that there is a correlation between the matrix structure of the actuator membrane and the fluid pumping flow rate. The injection flow rate of the EM micropump can be controlled by adjusting the input power supplied to the EM coil, and this is believed to improve the injection accuracy of the drug dosage and have potential in improving the proficiency of the existing drug delivery system. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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4455 KiB  
Article
Rhombic-Shaped Channel Stent with Enhanced Drug Capacity and Fatigue Life
by Hao-Ming Hsiao, Cheng-Han Lin, Yung-Kang Shen, Tzu-Yun Chou and Yen-Yu Hsu
Micromachines 2018, 9(1), 3; https://doi.org/10.3390/mi9010003 - 24 Dec 2017
Cited by 6 | Viewed by 6328
Abstract
A drug-eluting stent with rhombic-shaped drug reservoirs is proposed, aimed at providing long-term drug delivery and enhanced fatigue life. Unique rhombic-shaped reservoirs or channels on the stent struts can increase the total drug capacity and improve the stress distribution for longer fatigue life, [...] Read more.
A drug-eluting stent with rhombic-shaped drug reservoirs is proposed, aimed at providing long-term drug delivery and enhanced fatigue life. Unique rhombic-shaped reservoirs or channels on the stent struts can increase the total drug capacity and improve the stress distribution for longer fatigue life, without compromising other important clinical attributes. Our rhombic-shaped channel stent increases the total drug capacity by multiple times. Its fatigue safety factor, even with the large rhombic cutouts on the stent struts, could be 50% higher than that of the conventional drug-eluting stent. A pulsed fiber-optic laser and a series of expansions and heat treatments were used to make the first prototype of our rhombic-shaped channel stent. This new concept may open up a wide variety of new treatment options and opportunities for the medical industry in the future. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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7655 KiB  
Article
Integrated Lateral Flow Device for Flow Control with Blood Separation and Biosensing
by Veronica Betancur, Jianbo Sun, Nianqiang Wu and Yuxin Liu
Micromachines 2017, 8(12), 367; https://doi.org/10.3390/mi8120367 - 20 Dec 2017
Cited by 9 | Viewed by 6318
Abstract
Lateral flow devices are versatile and serve a wide variety of purposes, including medical, agricultural, environmental, and military applications. Yet, the most promising opportunities of these devices for diagnosis might reside in point-of-care (POC) applications. Disposable paper-based lateral flow strips have been of [...] Read more.
Lateral flow devices are versatile and serve a wide variety of purposes, including medical, agricultural, environmental, and military applications. Yet, the most promising opportunities of these devices for diagnosis might reside in point-of-care (POC) applications. Disposable paper-based lateral flow strips have been of particular interest, because they utilize low-cost materials and do not require expensive fabrication instruments. However, there are constraints on tuning flow rates and immunoassays functionalization in papers, as well as technical challenges in sensors’ integration and concentration units for low-abundant molecular detection. In the present work, we demonstrated an integrated lateral flow device that applied the capillary forces with functionalized polymer-based microfluidics as a strategy to realize a portable, simplified, and self-powered lateral flow device (LFD). The polydimethylsiloxane (PDMS) surface was rendered hydrophilic via functionalization with different concentrations of Pluronic F127. Controlled flow is a key variable for immunoassay-based applications for providing enough time for protein binding to antibodies. The flow rate of the integrated LFD was regulated by the combination of multiple factors, including Pluronic F127 functionalized surface properties and surface treatments of microchannels, resistance of the integrated flow resistor, the dimensions of the microstructures and the spacing between them in the capillary pump, the contact angles, and viscosity of the fluids. Various plasma flow rates were regulated and achieved in the whole device. The LFD combined the ability to separate high quality plasma from human whole blood by using a highly asymmetric plasma separation membrane, and created controlled and steady fluid flow using capillary forces produced by the interfacial tensions. Biomarker immunoglobulin G (IgG) detection from plasma was demonstrated with a graphene nanoelectronic sensor integrated with the LFD. The developed LFD can be used as a flexible and versatile platform, and has the potential for detecting circulating biomarkers from whole blood. Sandwich-immunoassays can be performed directly on the LFD by patterning receptors for analytes on a desired substrate, and detections can be performed using a variety of sensing methods including nanoelectronic, colorimetric, or fluorescence sensors. The described bio-sensing technology presents an alternative for POC testing using small samples of human whole blood. It could benefit regions with limited access to healthcare, where delays in diagnosis can lead to quick deterioration of the quality of life and increase the morbidity and mortality. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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3491 KiB  
Article
Electrical Tweezer for Droplet Transportation, Extraction, Merging and DNA Analysis
by Ali Shahid, Sylvia Chong, James Mahony, M. Jamal Deen and P. Ravi Selvaganapathy
Micromachines 2017, 8(12), 353; https://doi.org/10.3390/mi8120353 - 30 Nov 2017
Cited by 1 | Viewed by 4596
Abstract
Droplets of aqueous solutions distributed in an immiscible oil phase are increasingly used and investigated as a means to handle and assay small volumes of samples. The primary attraction of this method is that surface interactions are kept to a minimum, and changes [...] Read more.
Droplets of aqueous solutions distributed in an immiscible oil phase are increasingly used and investigated as a means to handle and assay small volumes of samples. The primary attraction of this method is that surface interactions are kept to a minimum, and changes in sample concentration, especially due to adsorption to the walls, are avoided. Microfluidic methods to generate, transport, merge, split and perform reactions in droplets were developed recently. These methods depend on the continuous flow of the two phases involved inside closed microfluidic channels. Alternatively, an electrowetting phenomenon was also exploited to control the movement of droplets between two solid substrates. However, there are some situations where small volume sample transport and assaying are required in open systems. Here, we demonstrate a simple electromechanical probe (tweezers) that is capable of manipulating a small aqueous droplet in a bi-layer oil phase. The tweezer consists of two needles positioned close to each other and uses polarization of the aqueous droplet in an applied electrical field to confine the droplet between the needles with minimal solid contact. Mechanical motion of the tweezer can be used to transport the droplet to various positions. Operations such as aliquoting, merging and transport are demonstrated. Finally, this method was used to perform a DNA amplification assay where droplets of the sample and the amplification mixture are aliquoted separately, mixed and amplified using an in-situ heater. This electromechanical tweezer is of interest in low-throughput, small-volume biological and chemical assays where the investigator requires direct and open access to the samples. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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4539 KiB  
Article
An Electromagnetically Actuated Double-Sided Cell-Stretching Device for Mechanobiology Research
by Harshad Kamble, Raja Vadivelu, Mathew Barton, Kseniia Boriachek, Ahmed Munaz, Sungsu Park, Muhammad J. A. Shiddiky and Nam-Trung Nguyen
Micromachines 2017, 8(8), 256; https://doi.org/10.3390/mi8080256 - 22 Aug 2017
Cited by 19 | Viewed by 7259
Abstract
Cellular response to mechanical stimuli is an integral part of cell homeostasis. The interaction of the extracellular matrix with the mechanical stress plays an important role in cytoskeleton organisation and cell alignment. Insights from the response can be utilised to develop cell culture [...] Read more.
Cellular response to mechanical stimuli is an integral part of cell homeostasis. The interaction of the extracellular matrix with the mechanical stress plays an important role in cytoskeleton organisation and cell alignment. Insights from the response can be utilised to develop cell culture methods that achieve predefined cell patterns, which are critical for tissue remodelling and cell therapy. We report the working principle, design, simulation, and characterisation of a novel electromagnetic cell stretching platform based on the double-sided axial stretching approach. The device is capable of introducing a cyclic and static strain pattern on a cell culture. The platform was tested with fibroblasts. The experimental results are consistent with the previously reported cytoskeleton reorganisation and cell reorientation induced by strain. Our observations suggest that the cell orientation is highly influenced by external mechanical cues. Cells reorganise their cytoskeletons to avoid external strain and to maintain intact extracellular matrix arrangements. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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