Microfluidic Systems for Biomedical Analysis, Detection and Diagnosis

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

Deadline for manuscript submissions: 31 March 2025 | Viewed by 9916

Special Issue Editor


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Guest Editor
Biomedical Engineering Department, University of Melbourne, Melbourne 3010, Australia
Interests: acoustofluidics; lab-on-a-chip; bioprinting
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Special Issue Information

Dear Colleagues,

Microfluidic systems are ideal for manipulating cellular and tissue environments, with the ability to define chemical concentrations, fluidic flow and cell positions down to the microscale. Such devices have accordingly found increasing use in enhancing biological and medical research, with the benefits for biomedical analysis, detection and diagnosis, including improved system integration, shorter assay times, smaller reaction volumes and reduced cost compared to conventional processes. Beyond this, microfluidic devices and principles have also been instrumental in fundamental biological studies.

For this Special Issue, we seek research contributions and review articles that examine the use of microsystems and microfluidic devices for biomedical applications. This includes the processing of biological samples, encompassing cells, tissues, organisms and biologically relevant materials such as proteins, cell media or DNA. Example activities in this space include sample preparation, high throughput sorting, cell analysis and point-of-care diagnosis in lab-on-a-chip devices.
Authors are encouraged to contact the editors if they have any questions regarding the suitability of their work for this Special Issue.

Dr. David J. Collins
Guest Editor

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Keywords

  • microfluidics
  • microsystems
  • lab-on-a-chip
  • electrophoresis
  • tissue engineering
  • acoustofluidics
  • hydrodynamics
  • optical tweezers
  • micromanipulation
  • lab-on-a-disk
  • organ-on-a-chip
  • drug discovery
  • diagnosis
  • cell analysis
  • bioassay

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Published Papers (6 papers)

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Research

10 pages, 7585 KiB  
Article
Monitoring Escherichia coli in Water through Real-Time Loop-Mediated Isothermal Amplification on Biochips
by Yuxin Wang, Yun-Sheng Chan, Eugene Lee, Donglu Shi, Chen-Yi Lee and Jiajie Diao
Micromachines 2024, 15(9), 1112; https://doi.org/10.3390/mi15091112 - 31 Aug 2024
Viewed by 1090
Abstract
Access to clean water is fundamental to public health and safety, serving as the cornerstone of well-being in communities. Despite the significant investments of millions of dollars in water testing and treatment processes, the United States continues to grapple with over 7 million [...] Read more.
Access to clean water is fundamental to public health and safety, serving as the cornerstone of well-being in communities. Despite the significant investments of millions of dollars in water testing and treatment processes, the United States continues to grapple with over 7 million waterborne-related cases annually. This persistent challenge underscores the pressing need for the development of a new, efficient, rapid, low-cost, and reliable method for ensuring water quality. The urgency of this endeavor cannot be overstated, as it holds the potential to safeguard countless lives and mitigate the pervasive risks associated with contaminated water sources. In this study, we introduce a biochip LAMP assay tailored for water source monitoring. Our method swiftly detects even extremely low concentrations of Escherichia coli (E. coli) in water, and 10 copies/μL of E. coli aqueous solution could yield positive results within 15 min on a PC-MEDA biochip. This innovation marks a significant departure from the current reliance on lab-dependent methods, which typically necessitate several days for bacterial culture and colony counting. Our multifunctional biochip system not only enables the real-time LAMP testing of crude E. coli samples but also holds promise for future modifications to facilitate on-site usage, thereby revolutionizing water quality assessment and ensuring rapid responses to potential contamination events. Full article
(This article belongs to the Special Issue Microfluidic Systems for Biomedical Analysis, Detection and Diagnosis)
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17 pages, 3910 KiB  
Article
Fabrication of Cost-Effective Microchip-Based Device Using Sandblasting Technique for Real-Time Multiplex PCR Detection
by Yiteng Liu, Zhiyang Hu, Siyu Yang, Na Xu, Qi Song, Yibo Gao and Weijia Wen
Micromachines 2024, 15(8), 944; https://doi.org/10.3390/mi15080944 - 24 Jul 2024
Viewed by 992
Abstract
The combination of multiplex polymerase chain reaction (mPCR) and microfluidic technologies demonstrates great significance in biomedical applications. However, current microfluidics-based molecular diagnostics face challenges in multi-target detection due to their limited fluorescence channels, complicated fabrication process, and high cost. In this research, we [...] Read more.
The combination of multiplex polymerase chain reaction (mPCR) and microfluidic technologies demonstrates great significance in biomedical applications. However, current microfluidics-based molecular diagnostics face challenges in multi-target detection due to their limited fluorescence channels, complicated fabrication process, and high cost. In this research, we proposed a cost-effective sandblasting method for manufacturing silicon microchips and a chip-based microdevice for field mPCR detection. The atomic force microscopy (AFM) images showed a rough surface of the sandblasted microchips, leading to poor biocompatibility. To relieve the inhibitory effect, we dip-coated a layer of bovine serum albumin (BSA) on the irregular substrate. The optimized coating condition was determined by scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) (65 °C for 60 min). After sufficient coating, we performed on-chip PCR tests with 500 copies/mL Coronavirus Disease 2019 (COVID-19) standard sample within 20 min, and the sandblasted microchip displayed a higher amplification rate compared to dry etching chips. Finally, we achieved a 50 min mPCR for screening five resistance genes of the endophthalmitis pathogens on our microdevices, with strong specificity and reliability. Thus, this sandblasted microchip-based platform not only provides a rapid, accessible, and effective solution for multiplex molecular detection but also enables large-scale microfabrication in a low-cost and convenient way. Full article
(This article belongs to the Special Issue Microfluidic Systems for Biomedical Analysis, Detection and Diagnosis)
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20 pages, 4136 KiB  
Article
Achieving High-Precision, Low-Cost Microfluidic Chip Fabrication with Flexible PCB Technology
by Andres Vanhooydonck, Thalissa Caers, Marc Parrilla, Peter Delputte and Regan Watts
Micromachines 2024, 15(4), 425; https://doi.org/10.3390/mi15040425 - 22 Mar 2024
Cited by 1 | Viewed by 2543
Abstract
Soft lithography has long remained the state of the art to generate the necessary micropatterning for molded microfluidic (MF) chips. Previous attempts to use printed circuit boards (PCBs) as a cheap and accessible alternative to expensive lithographed molds for the production of PDMS [...] Read more.
Soft lithography has long remained the state of the art to generate the necessary micropatterning for molded microfluidic (MF) chips. Previous attempts to use printed circuit boards (PCBs) as a cheap and accessible alternative to expensive lithographed molds for the production of PDMS MF chip prototypes have shown their limitations. A more in-depth exploration of using PCBs as a mold substrate and a novel methodology of using flexible PCBs to produce highly accurate MF chips is reported here for the first time. Cross sections highlight the improved accuracy of this method, and peel testing is performed to demonstrate suitable adhesion between the glass substrate and PDMS cast. Positive cell growth viability showcases this novel method as a high-accuracy, high-accessibility, low-cost prototyping method for microfluidic chips while still maintaining all favorable properties provided by the PDMS material. Full article
(This article belongs to the Special Issue Microfluidic Systems for Biomedical Analysis, Detection and Diagnosis)
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14 pages, 5274 KiB  
Article
Development of Drug Efficacy Testing Platform for Glomerulonephritis
by Eun-Jeong Kwon, Yunyeong Choi, Shin Young Kim, Seokwoo Park, Giae Yun, Sei Hong Min and Sejoong Kim
Micromachines 2024, 15(3), 317; https://doi.org/10.3390/mi15030317 - 24 Feb 2024
Cited by 1 | Viewed by 1267
Abstract
We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring a gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells with a bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, [...] Read more.
We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring a gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells with a bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, and reduced WT1 and nephrin compared to the normal GFB. Tacrolimus restored cell viability, reduced albumin permeability, and increased WT1 expression. Using serum from five membranous nephropathy (MN) patients, we created MN models using a GFB-mimicking chip. A notable decline in cell viability was observed in the serum-induced MN1 and MN2 models. However, tacrolimus restored it. Albumin permeability was reduced in the MN1, MN2, and MN5 models by tacrolimus treatment. MN1 displayed the best clinical response to tacrolimus, exhibiting increased expression of WT1 in chip-based evaluations after tacrolimus treatment. We successfully evaluated the efficacy of tacrolimus using puromycin-induced and serum-induced GN models on a chip that mimicked the structure and function of the GFB. The GFB-mimicking chip holds promise as a personalized platform for assessing drug efficacy using patient serum samples. Full article
(This article belongs to the Special Issue Microfluidic Systems for Biomedical Analysis, Detection and Diagnosis)
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12 pages, 4359 KiB  
Article
A Rapid Prototyping Approach for Multi-Material, Reversibly Sealed Microfluidics
by Michael Halwes, Melanie Stamp and David J. Collins
Micromachines 2023, 14(12), 2213; https://doi.org/10.3390/mi14122213 - 7 Dec 2023
Cited by 2 | Viewed by 1554
Abstract
Microfluidic organ-on-chip models recapitulate increasingly complex physiological phenomena to study tissue development and disease mechanisms, where there is a growing interest in retrieving delicate biological structures from these devices for downstream analysis. Standard bonding techniques, however, often utilize irreversible sealing, making sample retrieval [...] Read more.
Microfluidic organ-on-chip models recapitulate increasingly complex physiological phenomena to study tissue development and disease mechanisms, where there is a growing interest in retrieving delicate biological structures from these devices for downstream analysis. Standard bonding techniques, however, often utilize irreversible sealing, making sample retrieval unfeasible or necessitating destructive methods for disassembly. To address this, several commercial devices employ reversible sealing techniques, though integrating these techniques into early-stage prototyping workflows is often ignored because of the variation and complexity of microfluidic designs. Here, we demonstrate the concerted use of rapid prototyping techniques, including 3D printing and laser cutting, to produce multi-material microfluidic devices that can be reversibly sealed. This is enhanced via the incorporation of acrylic components directly into polydimethylsiloxane channel layers to enhance stability, sealing, and handling. These acrylic components act as a rigid surface separating the multiple mechanical seals created between the bottom substrate, the microfluidic features in the device, and the fluidic interconnect to external tubing, allowing for greater design flexibility. We demonstrate that these devices can be produced reproducibly outside of a cleanroom environment and that they can withstand ~1 bar pressures that are appropriate for a wide range of biological applications. By presenting an accessible and low-cost method, we hope to enable microfluidic prototyping for a broad range of biomedical research applications. Full article
(This article belongs to the Special Issue Microfluidic Systems for Biomedical Analysis, Detection and Diagnosis)
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11 pages, 5101 KiB  
Article
A Novel Electrokinetic-Based Technique for the Isolation of Circulating Tumor Cells
by Mohammad K. D. Manshadi, Mahsa Saadat, Mehdi Mohammadi and Amir Sanati Nezhad
Micromachines 2023, 14(11), 2062; https://doi.org/10.3390/mi14112062 - 5 Nov 2023
Viewed by 1567
Abstract
The separation of rare cells from complex biofluids has attracted attention in biological research and clinical applications, especially for cancer detection and treatment. In particular, various technologies and methods have been developed for the isolation of circulating tumor cells (CTCs) in the blood. [...] Read more.
The separation of rare cells from complex biofluids has attracted attention in biological research and clinical applications, especially for cancer detection and treatment. In particular, various technologies and methods have been developed for the isolation of circulating tumor cells (CTCs) in the blood. Among them, the induced-charge electrokinetic (ICEK) flow method has shown its high efficacy for cell manipulation where micro-vortices (MVs), generated as a result of induced charges on a polarizable surface, can effectively manipulate particles and cells in complex fluids. While the majority of MVs have been induced by AC electric fields, these vortices have also been observed under a DC electric field generated around a polarizable hurdle. In the present numerical work, the capability of MVs for the manipulation of CTCs and their entrapment in the DC electric field is investigated. First, the numerical results are verified against the available data in the literature. Then, various hurdle geometries are employed to find the most effective geometry for MV-based particle entrapment. The effects of electric field strength (EFS), wall zeta potential magnitude, and the particles’ diameter on the trapping efficacy are further investigated. The results demonstrated that the MVs generated around only the rectangular hurdle are capable of trapping particles as large as the size of CTCs. An EFS of about 75 V/cm was shown to be effective for the entrapment of above 90% of CTCs in the MVs. In addition, an EFS of 85 V/cm demonstrated a capability for isolating particles larger than 8 µm from a suspension of particles/cells 1–25 µm in diameter, useful for the enrichment of cancer cells and potentially for the real-time and non-invasive monitoring of drug effectiveness on circulating cancer cells in blood circulation. Full article
(This article belongs to the Special Issue Microfluidic Systems for Biomedical Analysis, Detection and Diagnosis)
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