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Biomedical Microfluidic Devices

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

Deadline for manuscript submissions: closed (30 June 2017) | Viewed by 84409

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Special Issue Editor

Prof. Dr. Kwang W. Oh

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Guest Editor

1. Sensors and MicroActuators Learning Lab (SMALL), Department of Electrical Engineering, The State University of New York at Buffalo, Buffalo, NY 14260, USA
2. Department of Biomedical Engineering, University at Buffalo, State University of New York (SUNY-Buffalo), Buffalo, NY 14260, USA
Interests: bioMEMS; lab-on-a-chip (LOC); microfluidics; droplet-based microfluidics; blood separation; micro PCR; micro SERS; sensors for LOC
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Special Issue Information

Dear Colleagues,

One of the greatest challenges of researchers using microfluidics is to develop novel microfluidic devices for the enhancement of their capabilities in biology and medical research. Many biomedical microfluidic devices have been miniaturized to replace conventional bioassays and diagnostics, featuring high bioassay performance, high system integration, improved potential for automation and control, small volume of samples and reagents, reduced cost, greater reliability and sensitivity, disposability and shorter bioassay times.

In this Special Issue, we solicit review articles and original research papers addressing technical challenges on developing microfluidic devices for biomedical and diagnostics applications. The papers can cover all aspects of biomedical microfluidic devices including, but not limited to, recent developments in the following areas: biomedical microfluidic devices; DNA, protein, cell, organism, tissue and organ on chip; diagnostics and theranostics; drug discovery and delivery; lab on chip (LOC); manipulation of biomolecules and biofluids; micro total analysis (mTAS); miniaturization of bioassays; and point of care (POC) devices.

Authors are invited to contact the guest editors prior to submission if they are uncertain whether their work falls within the general scope of this Special Issue on "Biomedical Microfluidic Devices".

Prof. Dr. Kwang W. Oh
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 submissions that pass pre-check are 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 2600 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

biomedical microfluidic devices
diagnostics
DNA, protein, cell, organism, tissue and organ on chip
drug discovery and delivery
lab on chip (LOC)
manipulation of biomolecules and biofluids
micro total analysis (mTAS)
miniaturization of bioassays
point of care (POC) devices
theranostics

Published Papers (13 papers)

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Editorial

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161 KiB

Open AccessEditorial

Multidisciplinary Role of Microfluidics for Biomedical and Diagnostic Applications: Biomedical Microfluidic Devices

by Kwang W. Oh

Micromachines 2017, 8(12), 343; https://doi.org/10.3390/mi8120343 - 27 Nov 2017

Cited by 11 | Viewed by 3588

Abstract

Life scientists are closely working with engineers to solve biological and biomedical problems through the application of engineering tools.[...] Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

Research

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5481 KiB

Open AccessArticle

A Fluidic Interface with High Flow Uniformity for Reusable Large Area Resonant Biosensors

by Charles-Louis Azzopardi, Vivien Lacour, Jean-François Manceau, Magali Barthès, Dimitri Bonnet, Franck Chollet and Thérèse Leblois

Micromachines 2017, 8(10), 308; https://doi.org/10.3390/mi8100308 - 14 Oct 2017

Cited by 4 | Viewed by 4691

Abstract

Resonant biosensors are known for their high accuracy and high level of miniaturization. However, their fabrication costs prevent them from being used as disposable sensors and their effective commercial success will depend on their ability to be reused repeatedly. Accordingly, all the parts of the sensor in contact with the fluid need to tolerate the regenerative process which uses different chemicals (H₃PO₄, H₂SO₄ based baths) without degrading the characteristics of the sensor. In this paper, we propose a fluidic interface that can meet these requirements, and control the liquid flow uniformity at the surface of the vibrating area. We study different inlet and outlet channel configurations, estimating their performance using numerical simulations based on finite element method (FEM). The interfaces were fabricated using wet chemical etching on Si, which has all the desirable characteristics for a reusable biosensor circuit. Using a glass cover, we could observe the circulation of liquid near the active surface, and by using micro-particle image velocimetry (μPIV) on large surface area we could verify experimentally the effectiveness of the different designs and compare with simulation results. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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4149 KiB

Open AccessArticle

Electroceutical Approach for Impairing the Motility of Pathogenic Bacterium Using a Microfluidic Platform

by Ryan Berthelot, Kristina Doxsee and Suresh Neethirajan

Micromachines 2017, 8(7), 207; https://doi.org/10.3390/mi8070207 - 29 Jun 2017

Cited by 4 | Viewed by 4981

Abstract

Electrotaxis, or galvanotaxis, refers to the migration pattern of cells induced in response to electrical potential. Electrotaxis has not been explored in detail in bacterial cells; information regarding the impact of current on pathogenic bacteria is severely lacking. Using microfluidic platforms and optical microscopy, we designed a series of single- and multi-cue experiments to assess the impact of varying electrical currents and acetic acid concentrations on bacterial motility dynamics in pathogenic multi-drug resistant (MDR) strains of Pseudomonas aeruginosa and Escherichia coli. The use of the microfluidic platform allows for single-cue experiments where electrical current is supplied at a range that is biocidal to bacteria and multi-cue experiments where acetic acid is combined with current to enhance disinfection. These strategies may offer substantial therapeutic benefits, specifically for the treatment of biofilm infections, such as those found in the wound environment. Our results showed that an application of current in combination with acetic acid has profound inhibitory effects on MDR strains of P. aeruginosa and E. coli, even with brief applications. Specifically, E. coli motility dynamics and cell survival were significantly impaired starting at a concentration of 0.125 mA of direct current (DC) and 0.31% acetic acid, while P. aeruginosa was impaired at 0.70 mA and 0.31% acetic acid. As these strains are relevant wound pathogens, it is likely that this strategy would be effective against similar strains in vivo and could represent a new approach to hasten wound healing. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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3424 KiB

Open AccessArticle

Hollow Hydrogel Microfiber Encapsulating Microorganisms for Mass-Cultivation in Open Systems

by Kazuhiko Higashi, Miho Ogawa, Kazuma Fujimoto, Hiroaki Onoe and Norihisa Miki

Micromachines 2017, 8(6), 176; https://doi.org/10.3390/mi8060176 - 03 Jun 2017

Cited by 7 | Viewed by 5842

Abstract

Open cultivation systems to monoculture microorganisms are promising for the commercialization of low-value commodities because they reduce the cultivation cost. However, contamination from biological pollutants frequently impedes the process. Here we propose a cultivation method using hollow hydrogel microfibers encapsulating microorganisms. Due to the pore size, hydrogels allow nutrients and waste to pass through while preventing invading microorganisms from entering the microfiber. Experimental cultivation shows the growth of target bacteria inside the alginate hydrogel microfiber during exposure to invading bacteria. The membrane thickness of the microfiber greatly affects the bacterial growth due to changes in membrane permeability. The enhancement of mechanical toughness is also demonstrated by employing a double-network hydrogel for long-term cultivation. The hollow hydrogel microfiber has the potential to become a mainstream solution for mass-cultivation of microorganisms in an open system. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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1728 KiB

Open AccessArticle

A Multiplexed Microfluidic Platform for Bone Marker Measurement: A Proof-of-Concept

by Patricia Khashayar, Ghassem Amoabediny, Bagher Larijani, Morteza Hosseini, Rik Verplancke, David Schaubroeck, Steven Van Put, Farideh Razi, Michel De Keersmaecker, Annemie Adriaens, Stefan Goemaere, Tom Fiers and Jan Vanfleteren

Micromachines 2017, 8(5), 133; https://doi.org/10.3390/mi8050133 - 25 Apr 2017

Cited by 8 | Viewed by 3933

Abstract

In this work, we report a microfluidic platform that can be easily translated into a biomarker diagnostic. This platform integrates microfluidic technology with electrochemical sensing and embodies a reaction/detection chamber to measure serum levels of different biomarkers. Microfabricated Au electrodes encased in a microfluidic chamber are functionalized to immobilize the antibodies, which can selectively capture the corresponding antigen. An oxidative peak is obtained using the chronoamperometry technique at room temperature. The magnitude of the response current varies linearly with the logarithmic concentration of the relative biomarker and, thus, is used to quantify the concentration of the relative biomarker in serum samples. We demonstrated the implementation, feasibility and specificity of this platform (Osteokit) in assaying serum levels of bone turnover markers (BTMs) using osteocalcin (limits of detection (LOD) = 1.94 ng/mL) and collagen type 1 cross-linked C-telopeptide (CTX) (LOD = 1.39 pg/mL). To our knowledge, this is the first such device fabricated to measure BTMs. Our results also showed that the sensitivity of Osteokit is comparable with the current states of art, electrochemiluminescence (ECLIA). Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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3526 KiB

Open AccessArticle

Red Blood Cell Responses during a Long-Standing Load in a Microfluidic Constriction

by Mitsuhiro Horade, Chia-Hung Dylan Tsai, Hiroaki Ito and Makoto Kaneko

Micromachines 2017, 8(4), 100; https://doi.org/10.3390/mi8040100 - 26 Mar 2017

Cited by 11 | Viewed by 5274

Abstract

Red blood cell responses during a long-standing load were experimentally investigated. With a high-speed camera and a high-speed actuator, we were able to manipulate cells staying inside a microfluidic constriction, and each cell was compressed due to the geometric constraints. During the load inside the constriction, the color of the cells was found to gradually darken, while the cell lengths became shorter and shorter. According to the analysis results of a 5 min load, the average increase of the cell darkness was 60.9 in 8-bit color resolution, and the average shrinkage of the cell length was 15% of the initial length. The same tendency was consistently observed from cell to cell. A correlation between the changes of the color and the length were established based on the experimental results. The changes are believed partially due to the viscoelastic properties of the cells that the cells’ configurations change with time for adapting to the confined space inside the constriction. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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16452 KiB

Open AccessArticle

Transfer Function of Macro-Micro Manipulation on a PDMS Microfluidic Chip

by Koji Mizoue, Kaoru Teramura, Chia-Hung Dylan Tsai and Makoto Kaneko

Micromachines 2017, 8(3), 80; https://doi.org/10.3390/mi8030080 - 04 Mar 2017

Cited by 7 | Viewed by 5113

Abstract

To achieve fast and accurate cell manipulation in a microfluidic channel, it is essential to know the true nature of its input-output relationship. This paper aims to reveal the transfer function of such a micro manipulation controlled by a macro actuator. Both a theoretical model and experimental results for the manipulation are presented. A second-order transfer function is derived based on the proposed model, where the polydimethylsiloxane (PDMS) deformation plays an important role in the manipulation. Experiments are conducted with input frequencies up to 300 Hz. An interesting observation from the experimental results is that the frequency responses of the transfer function behave just like a first-order integration operator in the system. The role of PDMS deformation for the transfer function is discussed based on the experimentally-determined parameters and the proposed model. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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2502 KiB

Open AccessArticle

The Optimization of a Microfluidic CTC Filtering Chip by Simulation

by Huan Li, Jianfeng Chen, Wenqiang Du, Youjun Xia, Depei Wang, Gang Zhao and Jiaru Chu

Micromachines 2017, 8(3), 79; https://doi.org/10.3390/mi8030079 - 04 Mar 2017

Cited by 11 | Viewed by 5471

Abstract

The detection and separation of circulating tumor cells (CTCs) are crucial in early cancer diagnosis and cancer prognosis. Filtration through a thin film is one of the size and deformability based separation methods, which can isolate rare CTCs from the peripheral blood of cancer patients regardless of their heterogeneity. In this paper, volume of fluid (VOF) multiphase flow models are employed to clarify the cells’ filtering processes. The cells may deform significantly when they enter a channel constriction, which will induce cell membrane stress and damage if the area strain is larger than the critical value. Therefore, the cellular damage criterion characterized by membrane area strain is presented in our model, i.e., the lysis limit of the lipid bilayer is taken as the critical area strain. Under this criterion, we discover that the microfilters with slit-shaped pores do less damage to cells than those with circular pores. The influence of contact angle between the microfilters and blood cells on cellular injury is also discussed. Moreover, the optimal film thickness and flux in our simulations are obtained as 0.5 μm and 0.375 mm/s, respectively. These findings will provide constructive guidance for the improvement of next generation microfilters with higher throughput and less cellular damage. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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6891 KiB

Open AccessArticle

An On-Chip RBC Deformability Checker Significantly Improves Velocity-Deformation Correlation

by Chia-Hung Dylan Tsai, Junichi Tanaka, Makoto Kaneko, Mitsuhiro Horade, Hiroaki Ito, Tatsunori Taniguchi, Tomohito Ohtani and Yasushi Sakata

Micromachines 2016, 7(10), 176; https://doi.org/10.3390/mi7100176 - 01 Oct 2016

Cited by 35 | Viewed by 6518

Abstract

An on-chip deformability checker is proposed to improve the velocity–deformation correlation for red blood cell (RBC) evaluation. RBC deformability has been found related to human diseases, and can be evaluated based on RBC velocity through a microfluidic constriction as in conventional approaches. The correlation between transit velocity and amount of deformation provides statistical information of RBC deformability. However, such correlations are usually only moderate, or even weak, in practical evaluations due to limited range of RBC deformation. To solve this issue, we implemented three constrictions of different width in the proposed checker, so that three different deformation regions can be applied to RBCs. By considering cell responses from the three regions as a whole, we practically extend the range of cell deformation in the evaluation, and could resolve the issue about the limited range of RBC deformation. RBCs from five volunteer subjects were tested using the proposed checker. The results show that the correlation between cell deformation and transit velocity is significantly improved by the proposed deformability checker. The absolute values of the correlation coefficients are increased from an average of 0.54 to 0.92. The effects of cell size, shape and orientation to the evaluation are discussed according to the experimental results. The proposed checker is expected to be useful for RBC evaluation in medical practices. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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4442 KiB

Open AccessFeature PaperArticle

Baking Powder Actuated Centrifugo-Pneumatic Valving for Automation of Multi-Step Bioassays

by David J. Kinahan, Marine Renou, Dirk Kurzbuch, Niamh A. Kilcawley, Éanna Bailey, Macdara T. Glynn, Colette McDonagh and Jens Ducrée

Micromachines 2016, 7(10), 175; https://doi.org/10.3390/mi7100175 - 01 Oct 2016

Cited by 17 | Viewed by 5577

Abstract

We report a new flow control method for centrifugal microfluidic systems; CO₂ is released from on-board stored baking powder upon contact with an ancillary liquid. The elevated pressure generated drives the sample into a dead-end pneumatic chamber sealed by a dissolvable film (DF). This liquid incursion wets and dissolves the DF, thus opening the valve. The activation pressure of the DF valve can be tuned by the geometry of the channel upstream of the DF membrane. Through pneumatic coupling with properly dimensioned disc architecture, we established serial cascading of valves, even at a constant spin rate. Similarly, we demonstrate sequential actuation of valves by dividing the disc into a number of distinct pneumatic chambers (separated by DF membranes). Opening these DFs, typically through arrival of a liquid to that location on a disc, permits pressurization of these chambers. This barrier-based scheme provides robust and strictly ordered valve actuation, which is demonstrated by the automation of a multi-step/multi-reagent DNA-based hybridization assay. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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2903 KiB

Open AccessArticle

A Simple Method for Fabrication of Microstructures Using a PDMS Stamp

by Hun Lee, Domin Koh, Linfeng Xu, Sindhu Row, Stelios T. Andreadis and Kwang W. Oh

Micromachines 2016, 7(10), 173; https://doi.org/10.3390/mi7100173 - 01 Oct 2016

Cited by 19 | Viewed by 10604

Abstract

We report a simple method to fabricate PDMS (polydimethylsiloxane) microwell arrays on glass by using a PDMS stamp to study cell-to-cell adhesion. In the cell-to-cell study, a glass substrate is required since glass has better cell attachment. The microwell arrays are replicated from an SU-8 master mold, and then are transferred to a glass substrate by lifting the PDMS stamp, followed by oxygen plasma bonding of the PDMS stamp on the glass substrate. For the cell-to-cell adhesion, four different types of PDMS arrays (e.g., rectangle, bowtie, wide-rhombus, and rhombus) were designed to vary the cell-to-cell contact length. The transfer success rates of the microwell arrays were measured as a function of both the contact area of the PDMS and the glass substrate and the different ratios between the base polymers and the curing agent. This method of generating the microwell arrays will enable a simple and robust construction of PDMS-based devices for various biological applications. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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Review

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17973 KiB

Open AccessReview

Towards Multiplex Molecular Diagnosis—A Review of Microfluidic Genomics Technologies

by Ismail Hussain Kamal Basha, Eric Tatt Wei Ho, Caffiyar Mohamed Yousuff and Nor Hisham Bin Hamid

Micromachines 2017, 8(9), 266; https://doi.org/10.3390/mi8090266 - 30 Aug 2017

Cited by 25 | Viewed by 10772

Abstract

Highly sensitive and specific pathogen diagnosis is essential for correct and timely treatment of infectious diseases, especially virulent strains, in people. Point-of-care pathogen diagnosis can be a tremendous help in managing disease outbreaks as well as in routine healthcare settings. Infectious pathogens can be identified with high specificity using molecular methods. A plethora of microfluidic innovations in recent years have now made it increasingly feasible to develop portable, robust, accurate, and sensitive genomic diagnostic devices for deployment at the point of care. However, improving processing time, multiplexed detection, sensitivity and limit of detection, specificity, and ease of deployment in resource-limited settings are ongoing challenges. This review outlines recent techniques in microfluidic genomic diagnosis and devices with a focus on integrating them into a lab on a chip that will lead towards the development of multiplexed point-of-care devices of high sensitivity and specificity. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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7987 KiB

Open AccessReview

Biomaterials Meet Microfluidics: From Synthesis Technologies to Biological Applications

by Jingyun Ma, Yachen Wang and Jing Liu

Micromachines 2017, 8(8), 255; https://doi.org/10.3390/mi8080255 - 19 Aug 2017

Cited by 54 | Viewed by 10648

Abstract

Microfluidics is characterized by laminar flow at micro-scale dimension, high surface to volume ratio, and markedly improved heat/mass transfer. In addition, together with advantages of large-scale integration and flexible manipulation, microfluidic technology has been rapidly developed as one of the most important platforms in the field of functional biomaterial synthesis. Compared to biomaterials assisted by conventional strategies, functional biomaterials synthesized by microfluidics are with superior properties and performances, due to their controllable morphology and composition, which have shown great advantages and potential in the field of biomedicine, biosensing, and tissue engineering. Take the significance of microfluidic engineered biomaterials into consideration; this review highlights the microfluidic synthesis technologies and biomedical applications of materials. We divide microfluidic based biomaterials into four kinds. According to the material dimensionality, it includes: 0D (particulate materials), 1D (fibrous materials), 2D (sheet materials), and 3D (construct forms of materials). In particular, micro/nano-particles and micro/nano-fibers are introduced respectively. This classification standard could include all of the microfluidic biomaterials, and we envision introducing a comprehensive and overall evaluation and presentation of microfluidic based biomaterials and their applications. Full article

(This article belongs to the Special Issue Biomedical Microfluidic Devices)

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