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Lab-on-a-Chip and Microfluidic Sensors

A special issue of Sensors (ISSN 1424-8220). This special issue belongs to the section "Physical Sensors".

Deadline for manuscript submissions: closed (19 February 2021) | Viewed by 34623

Special Issue Editor


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Guest Editor
Institute for Frontier Materials, Deakin University, Waurn Ponds, VIC 3216, Australia
Interests: lab on a chip; point of care device; low-cost; diagnostics; food safety; water analysis; sensors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lab-on-a-chip technology is the cornerstone of low-cost and robust testing at the point-of-care. It is widely applied for the semiquantitative detection of a broad range of target molecules in bodily fluids and water and food samples. However, it suffers from a major shortcoming that limits its usefulness, which is that it is mostly suitable for the analysis of simple analyte samples. For example, testing of blood biomarkers requires ex situ sample preprocessing (to obtain plasma), which negates the benefit of the point-of-care format. There is therefore a significant need to develop a next-generation point-of-care technology compatible with complex samples such as blood, tissue, stool, and food with greater limit-of-detection.

This Special Issue is devoted to covering microfluidic and lab-on-a-chip research that focuses on integrated sample preparation and detection on a single chip to provide low-cost and equipment-free detection. Some reviews constitute the backbone of the Special Issue, and there is room for many regular research papers, as well as mini reports.

Dr. Azadeh Nilghaz
Guest Editor

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Keywords

  • Lab-on-a-Chip devices
  • Microfluidics
  • Diagnostics
  • Food safety
  • Biosensors
  • Biochemistry
  • Analytical chemistry

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Published Papers (8 papers)

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16 pages, 3808 KiB  
Article
Opto-Microfluidic System for Absorbance Measurements in Lithium Niobate Device Applied to pH Measurements
by Riccardo Zamboni, Annamaria Zaltron, Elena Izzo, Gregorio Bottaro, Davide Ferraro and Cinzia Sada
Sensors 2020, 20(18), 5366; https://doi.org/10.3390/s20185366 - 19 Sep 2020
Cited by 14 | Viewed by 3241
Abstract
The aim of Lab-on-a-chip systems is the downscaling of analytical protocols into microfluidic devices, including optical measurements. In this context, the growing interest of the scientific community in opto-microfluidic devices has fueled the development of new materials. Recently, lithium niobate has been presented [...] Read more.
The aim of Lab-on-a-chip systems is the downscaling of analytical protocols into microfluidic devices, including optical measurements. In this context, the growing interest of the scientific community in opto-microfluidic devices has fueled the development of new materials. Recently, lithium niobate has been presented as a promising material for this scope, thanks to its remarkable optical and physicochemical properties. Here, we present a novel microfluidic device realized starting from a lithium niobate crystal, combining engraved microfluidic channels with integrated and self-aligned optical waveguides. Notably, the proposed microfabrication strategy does not compromise the optical coupling between the waveguides and the microchannel, allowing one to measure the transmitted light through the liquid flowing in the channel. In addition, the device shows a high versatility in terms of the optical properties of the light source, such as wavelength and polarization. Finally, the developed opto-microfluidic system is successfully validated as a probe for real-time pH monitoring of the liquid flowing inside the microchannel, showing a high integrability and fast response. Full article
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)
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13 pages, 5007 KiB  
Article
Rapid Detection of β-Lactamase-Producing Bacteria Using the Integrated Comprehensive Droplet Digital Detection (IC 3D) System
by Yiyan Li, Hemanth Cherukury, Louai Labanieh, Weian Zhao and Dong-Ku Kang
Sensors 2020, 20(17), 4667; https://doi.org/10.3390/s20174667 - 19 Aug 2020
Cited by 9 | Viewed by 4289
Abstract
Antibiotic-resistant bacteria have emerged as an imminent global threat. The lack of rapid and sensitive diagnostic techniques leaves health care providers with inadequate resources for guiding therapy and risks the lives of patients. The traditional plate culturing methods for identifying antibiotic-resistant bacteria is [...] Read more.
Antibiotic-resistant bacteria have emerged as an imminent global threat. The lack of rapid and sensitive diagnostic techniques leaves health care providers with inadequate resources for guiding therapy and risks the lives of patients. The traditional plate culturing methods for identifying antibiotic-resistant bacteria is laborious and time-consuming. Bulk PCR (Polymerase Chain Reaction) and qPCR are limited by poor detection sensitivity, which is critical for the early-stage detection of bloodstream infections. In this study, we introduce a technique for detecting β-lactamase-producing bacteria at single-cell sensitivity based on a commercial β-lactamase sensor (Fluorocillin), droplet microfluidics, and a custom 3D particle counter. Bacteria-containing samples were encapsulated within picoliter-sized droplets at the single-cell level and cultured within water-in-oil droplets containing antibiotics and the Fluorocillin sensor. Then, fluorescent droplets were digitally quantified with the 3D particle counter, which is capable of analyzing milliliter-scale volumes of collected droplets within 10 min. The fluorescence signal from single-colony droplets was detectable in less than 5 h, and the 3D scanning was performed in less than 10 min, which was significantly faster than conventional culture-based methods. In this approach, the limit of detection achieved was about 10 bacterial cells per mL of sample, and the turnaround time from sample to result was less than 6 h. This study demonstrates a promising strategy for the detection of β-lactamase-producing bacteria using the recently developed IC 3D system. Full article
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)
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17 pages, 4827 KiB  
Article
An Interface–Particle Interaction Approach for Evaluation of the Co-Encapsulation Efficiency of Cells in a Flow-Focusing Droplet Generator
by Mohammad Yaghoobi, Mohammad Said Saidi, Sepehr Ghadami and Navid Kashaninejad
Sensors 2020, 20(13), 3774; https://doi.org/10.3390/s20133774 - 5 Jul 2020
Cited by 9 | Viewed by 4033
Abstract
Droplet-based microfluidics offers significant advantages, such as high throughput and scalability, making platforms based on this technology ideal candidates for point-of-care (POC) testing and clinical diagnosis. However, the efficiency of co-encapsulation in droplets is suboptimal, limiting the applicability of such platforms for the [...] Read more.
Droplet-based microfluidics offers significant advantages, such as high throughput and scalability, making platforms based on this technology ideal candidates for point-of-care (POC) testing and clinical diagnosis. However, the efficiency of co-encapsulation in droplets is suboptimal, limiting the applicability of such platforms for the biosensing applications. The homogeneity of the bioanalytes in the droplets is an unsolved problem. While there is extensive literature on the experimental setups and active methods used to increase the efficiency of such platforms, passive techniques have received less attention, and their fundamentals have not been fully explored. Here, we develop a novel passive technique for investigating cell encapsulation using the finite element method (FEM). The level set method was used to track the interfaces of forming droplets. The effects of walls and the droplet interfaces on relatively large cells were calculated to track them more accurately during encapsulation. The static surface tension force was used to account for the effects of the interfaces on cells. The results revealed that the pairing efficiency is highly sensitive to the standard deviation (SD) of the distance between the cells in the entrance channel. The pairing efficiency prediction error of our model differed by less than 5% from previous experiments. The proposed model can be used to evaluate the performance of droplet-based microfluidic devices to ensure higher precision for co-encapsulation of cells. Full article
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)
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20 pages, 3139 KiB  
Article
Continuous-Flow Separation of Magnetic Particles from Biofluids: How Does the Microdevice Geometry Determine the Separation Performance?
by Cristina González Fernández, Jenifer Gómez Pastora, Arantza Basauri, Marcos Fallanza, Eugenio Bringas, Jeffrey J. Chalmers and Inmaculada Ortiz
Sensors 2020, 20(11), 3030; https://doi.org/10.3390/s20113030 - 27 May 2020
Cited by 20 | Viewed by 4085
Abstract
The use of functionalized magnetic particles for the detection or separation of multiple chemicals and biomolecules from biofluids continues to attract significant attention. After their incubation with the targeted substances, the beads can be magnetically recovered to perform analysis or diagnostic tests. Particle [...] Read more.
The use of functionalized magnetic particles for the detection or separation of multiple chemicals and biomolecules from biofluids continues to attract significant attention. After their incubation with the targeted substances, the beads can be magnetically recovered to perform analysis or diagnostic tests. Particle recovery with permanent magnets in continuous-flow microdevices has gathered great attention in the last decade due to the multiple advantages of microfluidics. As such, great efforts have been made to determine the magnetic and fluidic conditions for achieving complete particle capture; however, less attention has been paid to the effect of the channel geometry on the system performance, although it is key for designing systems that simultaneously provide high particle recovery and flow rates. Herein, we address the optimization of Y-Y-shaped microchannels, where magnetic beads are separated from blood and collected into a buffer stream by applying an external magnetic field. The influence of several geometrical features (namely cross section shape, thickness, length, and volume) on both bead recovery and system throughput is studied. For that purpose, we employ an experimentally validated Computational Fluid Dynamics (CFD) numerical model that considers the dominant forces acting on the beads during separation. Our results indicate that rectangular, long devices display the best performance as they deliver high particle recovery and high throughput. Thus, this methodology could be applied to the rational design of lab-on-a-chip devices for any magnetically driven purification, enrichment or isolation. Full article
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)
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12 pages, 2982 KiB  
Article
Miniaturized Continuous-Flow Digital PCR for Clinical-Level Serum Sample Based on the 3D Microfluidics and CMOS Imaging Device
by Bin Li, Yuanming Li, Andreas Manz and Wenming Wu
Sensors 2020, 20(9), 2492; https://doi.org/10.3390/s20092492 - 28 Apr 2020
Cited by 7 | Viewed by 4263
Abstract
In recent years, the development of polymerase chain reaction (PCR) technology has focused on digital PCR, which depends on the microfluidics. Based on continuous-flow microfluidic technology, this paper designed a miniaturized digital PCR amplification system, and greatly reduced the area required for microdroplet [...] Read more.
In recent years, the development of polymerase chain reaction (PCR) technology has focused on digital PCR, which depends on the microfluidics. Based on continuous-flow microfluidic technology, this paper designed a miniaturized digital PCR amplification system, and greatly reduced the area required for microdroplet generation and reaction. The core rod. made of polydimethylsiloxane (PDMS), was combined with the Teflon tube to form 3D microfluidics, which requires only one heating source to form the temperature difference required for gene amplification. Only two 34 g needles can form and transmit micro-droplets in a 4-fold tapered Teflon tube, which is the simplest method to generate digital PCR droplets as far as we know, which allows the microdroplet generation device to be free from dependence on expensive chips. A complementary metal oxide semiconductor (CMOS) camera was used as a detection tool to obtain fluorescence video for the entire loop area or a specified loop area. In addition, we developed a homebrew for automatic image acquisition and processing to realize the function of digital PCR. This technique realizes the analysis of clinical serum samples of hepatitis B virus (HBV) and obtained the same results as real-time quantitative PCR. This system has greatly reduced the size and cost of the entire system, while maintaining a stable response. Full article
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)
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14 pages, 4888 KiB  
Article
Digital Microfluidics for the Detection of Selected Inorganic Ions in Aerosols
by Shuquan Huang, Jessica Connolly, Andrei Khlystov and Richard B. Fair
Sensors 2020, 20(5), 1281; https://doi.org/10.3390/s20051281 - 27 Feb 2020
Cited by 23 | Viewed by 5113
Abstract
A prototype aerosol detection system is presented that is designed to accurately and quickly measure the concentration of selected inorganic ions in the atmosphere. The aerosol detection system combines digital microfluidics technology, aerosol impaction and chemical detection integrated on the same chip. Target [...] Read more.
A prototype aerosol detection system is presented that is designed to accurately and quickly measure the concentration of selected inorganic ions in the atmosphere. The aerosol detection system combines digital microfluidics technology, aerosol impaction and chemical detection integrated on the same chip. Target compounds are the major inorganic aerosol constituents: sulfate, nitrate and ammonium. The digital microfluidic system consists of top and bottom plates that sandwich a fluid layer. Nozzles for an inertial impactor are built into the top plate according to known, scaling principles. The deposited air particles are densely concentrated in well-defined deposits on the bottom plate containing droplet actuation electrodes of the chip in fixed areas. The aerosol collection efficiency for particles larger than 100 nm in diameter was higher than 95%. After a collection phase, deposits are dissolved into a scanning droplet. Due to a sub-microliter droplet size, the obtained extract is highly concentrated. Droplets then pass through an air/oil interface on chip for colorimetric analysis by spectrophotometry using optical fibers placed between the two plates of the chip. To create a standard curve for each analyte, six different concentrations of liquid standards were chosen for each assay and dispensed from on-chip reservoirs. The droplet mixing was completed in a few seconds and the final droplet was transported to the detection position as soon as the mixing was finished. Limits of detection (LOD) in the final droplet were determined to be 11 ppm for sulfate and 0.26 ppm for ammonium. For nitrate, it was impossible to get stable measurements. The LOD of the on-chip measurements for sulfate was close to that obtained by an off-chip method using a Tecan spectrometer. LOD of the on-chip method for ammonium was about five times larger than what was obtained with the off-chip method. For the current impactor collection air flow (1 L/min) and 1 h collection time, the converted LODs in air were: 0.275 μg/m3 for sulfate, 6.5 ng/m3 for ammonium, sufficient for most ambient air monitoring applications. Full article
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)
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12 pages, 848 KiB  
Article
A Hybrid Lab-on-a-Chip Injector System for Autonomous Carbofuran Screening
by Aristeidis S. Tsagkaris, Jana Pulkrabova, Jana Hajslova and Daniel Filippini
Sensors 2019, 19(24), 5579; https://doi.org/10.3390/s19245579 - 17 Dec 2019
Cited by 20 | Viewed by 4728
Abstract
Securing food safety standards is crucial to protect the population from health-threatening food contaminants. In the case of pesticide residues, reference procedures typically find less than 1% of tested samples being contaminated, thus indicating the necessity for new tools able to support smart [...] Read more.
Securing food safety standards is crucial to protect the population from health-threatening food contaminants. In the case of pesticide residues, reference procedures typically find less than 1% of tested samples being contaminated, thus indicating the necessity for new tools able to support smart and affordable prescreening. Here, we introduce a hybrid paper–lab-on-a-chip platform, which integrates on-demand injectors to perform multiple step protocols in a single disposable device. Simultaneous detection of enzymatic color response in sample and reference cells, using a regular smartphone, enabled semiquantitative detection of carbofuran, a neurotoxic and EU-banned carbamate pesticide, in a wide concentration range. The resulting evaluation procedure is generic and allows the rejection of spurious measurements based on their dynamic responses, and was effectively applied for the binary detection of carbofuran in apple extracts. Full article
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)
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9 pages, 2003 KiB  
Letter
Alginate Hydrogel-Embedded Capillary Sensor for Quantitative Immunoassay with Naked Eye
by Wenshu Zheng, Cen Gao, Liheng Shen, Chang Qu, Xuan Zhang, Lu Yang, Qiang Feng and Rongbing Tang
Sensors 2020, 20(17), 4831; https://doi.org/10.3390/s20174831 - 27 Aug 2020
Cited by 8 | Viewed by 3442
Abstract
We have developed an alginate hydrogel-embedded capillary sensor (AHCS) for naked eye-based quantification of immunoassay. Alkaline phosphatase (ALP) can modulate gel-sol transformation to increase the permeability of Cu2+-cross-linked alginate hydrogel film in the AHCS, followed by solution exchange into the capillary. [...] Read more.
We have developed an alginate hydrogel-embedded capillary sensor (AHCS) for naked eye-based quantification of immunoassay. Alkaline phosphatase (ALP) can modulate gel-sol transformation to increase the permeability of Cu2+-cross-linked alginate hydrogel film in the AHCS, followed by solution exchange into the capillary. Through measuring the length of the liquid phase of the microfluidics in the capillary at a given time, the concentration of the ALP could be quantified with the naked eye. Since ALP is widely applied as a signal reporter for immunoassays, the AHCS could easily accommodate conventional immune sensing platforms. We justify the practicality of AHCS with hepatitis B virus surface antigen (HBsAg) in serum samples and got comparable results with commercialized immunoassay. This AHCS is easy to make and use, effective in cost, and robust in quantification with the naked eye, showing great promise for next generation point-of-care testing. Full article
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)
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