Special Issue "Microelectrode Arrays and Application to Medical Devices"

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B:Biology and Biomedicine".

Deadline for manuscript submissions: closed (1 April 2020).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Colin Dalton
E-Mail Website
Guest Editor
Electrical and Computer Engineering Department, University of Calgary, Calgary, AB T2N 1N4, Canada
Interests: Biomedical micro devices; Brain Machine interfaces; Electrokinetics; Lab-on-a-chip; Micro/nano fabrication (MEMS, bioMEMS); Micro electrode arrays; Microfluidics
Special Issues and Collections in MDPI journals
Dr. Alinaghi Salari
E-Mail Website
Assistant Guest Editor
Institute for Biomedical Engineering, Science and Technology (IBEST), Li Ka Shing Knowledge Institute, 209 Victoria St, Toronto, ON M5B 1T8, Canada
Interests: Microfluidics; Lab-on-a-Chip; Electrokinetics; Cell Biology

Special Issue Information

Dear Colleagues,

Microelectrode arrays are increasingly used in a wide variety of situations in the medical device sector. For example, one major challenge in microfluidic devices is the manipulation of fluids and droplets effectively at such scales. Due to the laminar flow regime (i.e., low Reynolds number) in microfluidic devices, the mixing of species is also difficult, and unless an active mixing strategy is employed, passive diffusion is the only mechanism that causes the fluid to mix. For many applications, diffusion is considered too slow, and thus many active pumping and mixing strategies have been employed using electrokinetic methods, which utilize a variety of simple and complex microelectrode array structures.

Microelectrodes have also been implemented in in-vitro intracellular delivery platforms to conduct cell electroporation on chip, where a highly localized electric field on the scale of a single cell is generated to enhance the uptake of extracellular material. In addition, microelectrode arrays are utilized in different microfluidic biosensing modalities where a higher sensitivity, selectivity, and limit-of-detection are desired. Carbon nanotube microelectrode arrays are used for DNA detection, multi-electrode array chips are used for drug discovery, and there has been an explosion of research into brain–machine interfaces, fueled by microfabricated electrode arrays, both planar and three-dimensional.

The advantages associated with microelectrode arrays include small size, the ability to manufacture repeatedly and reliably tens to thousands of micro-electrodes on both rigid and flexible substrates, and their utility for both in vitro and in vivo applications. To realize their full potential, there is a need to develop and integrate microelectrode arrays to form useful medical device systems.

As the field of microelectrode array research is wide, and touches many application areas, it is often difficult to locate a single source of relevant information. This Special Issue seeks to showcase research papers, short communications, and review articles that focus on the application of microelectrode arrays in the medical device sector. Particular interest will be paid to innovative application areas that can improve upon existing medical devices, such as for neuromodulation and real world lab-on-a-chip applications.

Dr. Colin Dalton
Dr. Alinaghi Salari
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Micro Electrode Array
  • Biomedical Micro Devices
  • Brain Machine Interfaces
  • Electrokinetics
  • Lab-on-a-Chip
  • Microfluidics
  • Neuromodulcation
  • Biosensors
  • Micropumps
  • Micromixing
  • Electrothermal
  • Electroosmosis
  • Dielectrophoresis

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Published Papers (11 papers)

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Editorial

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Editorial
Editorial on the Special Issue on Microelectrode Arrays and Application to Medical Devices
Micromachines 2020, 11(8), 776; https://doi.org/10.3390/mi11080776 - 14 Aug 2020
Viewed by 540
Abstract
In this editorial note, we briefly review the major findings of the 10 articles published in the Special Issue on microelectrode arrays and application to medical devices [...] Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)

Research

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Article
Electrochemical Evaluation of a Multi-Site Clinical Depth Recording Electrode for Monitoring Cerebral Tissue Oxygen
Micromachines 2020, 11(7), 632; https://doi.org/10.3390/mi11070632 - 28 Jun 2020
Cited by 2 | Viewed by 859
Abstract
The intracranial measurement of local cerebral tissue oxygen levels—PbtO2—has become a useful tool for the critical care unit to investigate severe trauma and ischemia injury in patients. Our preliminary work in animal models supports the hypothesis that multi-site depth electrode recording [...] Read more.
The intracranial measurement of local cerebral tissue oxygen levels—PbtO2—has become a useful tool for the critical care unit to investigate severe trauma and ischemia injury in patients. Our preliminary work in animal models supports the hypothesis that multi-site depth electrode recording of PbtO2 may give surgeons and critical care providers needed information about brain viability and the capacity for better recovery. Here, we present a surface morphology characterization and an electrochemical evaluation of the analytical properties toward oxygen detection of an FDA-approved, commercially available, clinical grade depth recording electrode comprising 12 Pt recording contacts. We found that the surface of the recording sites is composed of a thin film of smooth Pt and that the electrochemical behavior evaluated by cyclic voltammetry in acidic and neutral electrolyte is typical of polycrystalline Pt surface. The smoothness of the Pt surface was further corroborated by determination of the electrochemical active surface, confirming a roughness factor of 0.9. At an optimal working potential of −0.6 V vs. Ag/AgCl, the sensor displayed suitable values of sensitivity and limit of detection for in vivo PbtO2 measurements. Based on the reported catalytical properties of Pt toward the electroreduction reaction of O2, we propose that these probes could be repurposed for multisite monitoring of PbtO2 in vivo in the human brain. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Article
Mechanically Robust, Softening Shape Memory Polymer Probes for Intracortical Recording
Micromachines 2020, 11(6), 619; https://doi.org/10.3390/mi11060619 - 25 Jun 2020
Cited by 2 | Viewed by 804
Abstract
While intracortical microelectrode arrays (MEAs) may be useful in a variety of basic and clinical scenarios, their implementation is hindered by a variety of factors, many of which are related to the stiff material composition of the device. MEAs are often fabricated from [...] Read more.
While intracortical microelectrode arrays (MEAs) may be useful in a variety of basic and clinical scenarios, their implementation is hindered by a variety of factors, many of which are related to the stiff material composition of the device. MEAs are often fabricated from high modulus materials such as silicon, leaving devices vulnerable to brittle fracture and thus complicating device fabrication and handling. For this reason, polymer-based devices are being heavily investigated; however, their implementation is often difficult due to mechanical instability that requires insertion aids during implantation. In this study, we design and fabricate intracortical MEAs from a shape memory polymer (SMP) substrate that remains stiff at room temperature but softens to 20 MPa after implantation, therefore allowing the device to be implanted without aids. We demonstrate chronic recordings and electrochemical measurements for 16 weeks in rat cortex and show that the devices are robust to physical deformation, therefore making them advantageous for surgical implementation. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Article
Microelectrode Array based Functional Testing of Pancreatic Islet Cells
Micromachines 2020, 11(5), 507; https://doi.org/10.3390/mi11050507 - 17 May 2020
Cited by 1 | Viewed by 1103
Abstract
Electrophysiological techniques to characterize the functionality of islets of Langerhans have been limited to short-term, one-time recordings such as a patch clamp recording. We describe the use of microelectrode arrays (MEAs) to better understand the electrophysiology of dissociated islet cells in response to [...] Read more.
Electrophysiological techniques to characterize the functionality of islets of Langerhans have been limited to short-term, one-time recordings such as a patch clamp recording. We describe the use of microelectrode arrays (MEAs) to better understand the electrophysiology of dissociated islet cells in response to glucose in a real-time, non-invasive method over prolonged culture periods. Human islets were dissociated into singular cells and seeded onto MEA, which were cultured for up to 7 days. Immunofluorescent imaging revealed that several cellular subtypes of islets; β, δ, and γ cells were present after dissociation. At days 1, 3, 5, and 7 of culture, MEA recordings captured higher electrical activities of islet cells under 16.7 mM glucose (high glucose) than 1.1 mM glucose (low glucose) conditions. The fraction of the plateau phase (FOPP), which is the fraction of time with spiking activity recorded using the MEA, consistently showed distinguishably greater percentages of spiking activity with high glucose compared to the low glucose for all culture days. In parallel, glucose stimulated insulin secretion was measured revealing a diminished insulin response after day 3 of culture. Additionally, MEA spiking profiles were similar to the time course of insulin response when glucose concentration is switched from 1.1 to 16.7 mM. Our analyses suggest that extracellular recordings of dissociated islet cells using MEA is an effective approach to rapidly assess islet functionality, and could supplement standard assays such as glucose stimulate insulin response. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Article
Transparent Microelectrode Arrays Fabricated by Ion Beam Assisted Deposition for Neuronal Cell In Vitro Recordings
Micromachines 2020, 11(5), 497; https://doi.org/10.3390/mi11050497 - 14 May 2020
Cited by 3 | Viewed by 1070
Abstract
Microelectrode array (MEA) is a tool used for recording bioelectric signals from electrically active cells in vitro. In this paper, ion beam assisted electron beam deposition (IBAD) has been used for depositing indium tin oxide (ITO) and titanium nitride (TiN) thin films which [...] Read more.
Microelectrode array (MEA) is a tool used for recording bioelectric signals from electrically active cells in vitro. In this paper, ion beam assisted electron beam deposition (IBAD) has been used for depositing indium tin oxide (ITO) and titanium nitride (TiN) thin films which are applied as transparent track and electrode materials in MEAs. In the first version, both tracks and electrodes were made of ITO to guarantee full transparency and thus optimal imaging capability. In the second version, very thin (20 nm) ITO electrodes were coated with a thin (40 nm) TiN layer to decrease the impedance of Ø30 µm electrodes to one third (1200 kΩ → 320 kΩ) while maintaining (partial) transparency. The third version was also composed of transparent ITO tracks, but the measurement properties were optimized by using thick (200 nm) opaque TiN electrodes. In addition to the impedance, the optical transmission and electric noise levels of all three versions were characterized and the functionality of the MEAs was successfully demonstrated using human pluripotent stem cell-derived neuronal cells. To understand more thoroughly the factors contributing to the impedance, MEAs with higher IBAD ITO thickness as well as commercial sputter-deposited and highly conductive ITO were fabricated for comparison. Even if the sheet-resistance of our IBAD ITO thin films is very high compared to the sputtered one, the impedances of the MEAs of each ITO grade were found to be practically equal (e.g., 300–370 kΩ for Ø30 µm electrodes with 40 nm TiN coating). This implies that the increased resistance of the tracks, either caused by lower thickness or lower conductivity, has hardly any contribution to the impedance of the MEA electrodes. The impedance is almost completely defined by the double-layer interface between the electrode top layer and the medium including cells. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Article
Buoyancy-Free Janus Microcylinders as Mobile Microelectrode Arrays for Continuous Microfluidic Biomolecule Collection within a Wide Frequency Range: A Numerical Simulation Study
Micromachines 2020, 11(3), 289; https://doi.org/10.3390/mi11030289 - 10 Mar 2020
Cited by 4 | Viewed by 1042
Abstract
We numerically study herein the AC electrokinetic motion of Janus mobile microelectrode (ME) arrays in electrolyte solution in a wide field frequency, which holds great potential for biomedical applications. A fully coupled physical model, which incorporates the fluid-structure interaction under the synergy of [...] Read more.
We numerically study herein the AC electrokinetic motion of Janus mobile microelectrode (ME) arrays in electrolyte solution in a wide field frequency, which holds great potential for biomedical applications. A fully coupled physical model, which incorporates the fluid-structure interaction under the synergy of induced-charge electroosmotic (ICEO) slipping and interfacial Maxwell stress, is developed for this purpose. A freely suspended Janus cylinder free from buoyancy, whose main body is made of polystyrene, while half of the particle surface is coated with a thin conducting film of negligible thickness, will react actively on application of an AC signal. In the low-frequency limit, induced-charge electrophoretic (ICEP) translation occurs due to symmetric breaking in ICEO slipping, which renders the insulating end to move ahead. At higher field frequencies, a brand-new electrokinetic transport phenomenon called “ego-dielectrophoresis (e-DEP)” arises due to the action of the localized uneven field on the inhomogeneous particle dipole moment. In stark contrast with the low-frequency ICEP translation, the high-frequency e-DEP force tends to drive the asymmetric dipole moment to move in the direction of the conducting end. The bidirectional transport feature of Janus microspheres in a wide AC frequency range can be vividly interpreted as an array of ME for continuous loading of secondary bioparticles from the surrounding liquid medium along its direction-controllable path by long-range electroconvection. These results pave the way for achieving flexible and high-throughput on-chip extraction of nanoscale biological contents for subsequent on-site bioassay based upon AC electrokinetics of Janus ME arrays. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Article
Low-Power, Multimodal Laser Micromachining of Materials for Applications in sub-5 µm Shadow Masks and sub-10 µm Interdigitated Electrodes (IDEs) Fabrication
Micromachines 2020, 11(2), 178; https://doi.org/10.3390/mi11020178 - 08 Feb 2020
Cited by 3 | Viewed by 1030
Abstract
Laser micromachining is a direct write microfabrication technology that has several advantages over traditional micro/nanofabrication techniques. In this paper, we present a comprehensive characterization of a QuikLaze 50ST2 multimodal laser micromachining tool by determining the ablation characteristics of six (6) different materials and [...] Read more.
Laser micromachining is a direct write microfabrication technology that has several advantages over traditional micro/nanofabrication techniques. In this paper, we present a comprehensive characterization of a QuikLaze 50ST2 multimodal laser micromachining tool by determining the ablation characteristics of six (6) different materials and demonstrating two applications. Both the thermodynamic theoretical and experimental ablation characteristics of stainless steel (SS) and aluminum are examined at 1064 nm, silicon and polydimethylsiloxane (PDMS) at 532 nm, and Kapton® and polyethylene terephthalate at 355 nm. We found that the experimental data aligned well with the theoretical analysis. Additionally, two applications of this multimodal laser micromachining technology are demonstrated: shadow masking down to approximately 1.5 µm feature sizes and interdigitated electrode (IDE) fabrication down to 7 µm electrode gap width. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Article
A Low Contact Impedance Medical Flexible Electrode Based on a Pyramid Array Micro-Structure
Micromachines 2020, 11(1), 57; https://doi.org/10.3390/mi11010057 - 01 Jan 2020
Cited by 3 | Viewed by 952
Abstract
Flexible electrodes are extensively used to detect signals in electrocardiography, electroencephalography, electro-ophthalmography, and electromyography, among others. These electrodes can also be used in wearable and implantable medical systems. The collected signals directly affect doctors’ diagnoses of patient etiology and are closely associated with [...] Read more.
Flexible electrodes are extensively used to detect signals in electrocardiography, electroencephalography, electro-ophthalmography, and electromyography, among others. These electrodes can also be used in wearable and implantable medical systems. The collected signals directly affect doctors’ diagnoses of patient etiology and are closely associated with patients’ life safety. Electrodes with low contact impedance can acquire good quality signals. Herein, we established a method of arraying pyramidal microstructures on polydimethylsiloxane (PDMS) substrates to increase the contact area of electrodes, and a parylene transitional layer is coated between PDMS substrates and metal membranes to enhance the bonding force, finally reducing the impedance of flexible electrodes. Experimental results demonstrated that the proposed methods were effective. The contact area of the fabricated electrode increased by 18.15% per unit area, and the contact impedance at 20 Hz to 1 kHz scanning frequency ranged from 23 to 8 kΩ, which was always smaller than that of a commercial electrode. Overall, these results indicated the excellent performance of the fabricated electrode given its low contact impedance and good biocompatibility. This study can also serve as a reference for further electrode research and application in wearable and implantable medical systems. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Article
Rapid and Sensitive Detection of Bisphenol A Based on Self-Assembly
Micromachines 2020, 11(1), 41; https://doi.org/10.3390/mi11010041 - 30 Dec 2019
Cited by 2 | Viewed by 806
Abstract
Bisphenol A (BPA) is an endocrine disruptor that may lead to reproductive disorder, heart disease, and diabetes. Infants and young children are likely to be vulnerable to the effects of BPA. At present, the detection methods of BPA are complicated to operate and [...] Read more.
Bisphenol A (BPA) is an endocrine disruptor that may lead to reproductive disorder, heart disease, and diabetes. Infants and young children are likely to be vulnerable to the effects of BPA. At present, the detection methods of BPA are complicated to operate and require expensive instruments. Therefore, it is quite vital to develop a simple, rapid, and highly sensitive method to detect BPA in different samples. In this study, we have designed a rapid and highly sensitive biosensor based on an effective self-assembled monolayer (SAM) and alternating current (AC) electrokinetics capacitive sensing method, which successfully detected BPA at nanomolar levels with only one minute. The developed biosensor demonstrates a detection of BPA ranging from 0.028 μg/mL to 280 μg/mL with a limit of detection (LOD) down to 0.028 μg/mL in the samples. The developed biosensor exhibited great potential as a portable BPA biosensor, and further development of this biosensor may also be useful in the detection of other small biochemical molecules. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Review

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Review
Advances in Liquid Metal-Enabled Flexible and Wearable Sensors
Micromachines 2020, 11(2), 200; https://doi.org/10.3390/mi11020200 - 15 Feb 2020
Cited by 15 | Viewed by 2512
Abstract
Sensors are core elements to directly obtain information from surrounding objects for further detecting, judging and controlling purposes. With the rapid development of soft electronics, flexible sensors have made considerable progress, and can better fit the objects to detect and, thus respond to [...] Read more.
Sensors are core elements to directly obtain information from surrounding objects for further detecting, judging and controlling purposes. With the rapid development of soft electronics, flexible sensors have made considerable progress, and can better fit the objects to detect and, thus respond to changes more sensitively. Recently, as a newly emerging electronic ink, liquid metal is being increasingly investigated to realize various electronic elements, especially soft ones. Compared to conventional soft sensors, the introduction of liquid metal shows rather unique advantages. Due to excellent flexibility and conductivity, liquid-metal soft sensors present high enhancement in sensitivity and precision, thus producing many profound applications. So far, a series of flexible and wearable sensors based on liquid metal have been designed and tested. Their applications have also witnessed a growing exploration in biomedical areas, including health-monitoring, electronic skin, wearable devices and intelligent robots etc. This article presents a systematic review of the typical progress of liquid metal-enabled soft sensors, including material innovations, fabrication strategies, fundamental principles, representative application examples, and so on. The perspectives of liquid-metal soft sensors is finally interpreted to conclude the future challenges and opportunities. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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Review
AC Electrothermal Effect in Microfluidics: A Review
Micromachines 2019, 10(11), 762; https://doi.org/10.3390/mi10110762 - 11 Nov 2019
Cited by 18 | Viewed by 1000
Abstract
The electrothermal effect has been investigated extensively in microfluidics since the 1990s and has been suggested as a promising technique for fluid manipulations in lab-on-a-chip devices. The purpose of this article is to provide a timely overview of the previous works conducted in [...] Read more.
The electrothermal effect has been investigated extensively in microfluidics since the 1990s and has been suggested as a promising technique for fluid manipulations in lab-on-a-chip devices. The purpose of this article is to provide a timely overview of the previous works conducted in the AC electrothermal field to provide a comprehensive reference for researchers new to this field. First, electrokinetic phenomena are briefly introduced to show where the electrothermal effect stands, comparatively, versus other mechanisms. Then, recent advances in the electrothermal field are reviewed from different aspects and categorized to provide a better insight into the current state of the literature. Results and achievements of different studies are compared, and recommendations are made to help researchers weigh their options and decide on proper configuration and parameters. Full article
(This article belongs to the Special Issue Microelectrode Arrays and Application to Medical Devices)
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