Paper-Based Biosensors

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Nano- and Micro-Technologies in Biosensors".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 36692

Special Issue Editors

School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China
Interests: biosensing based on functional nanomaterials; microfluidic paper-based devices; fabricating and controlling solid–liquid interface; non-invasive diagnosis
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Guest Editor
Department of Engineering Science, National Cheng Kung University, Tainan 70101, Taiwan
Interests: microfluidic systems; microfluidic paper-based devices; mems fabrication technologies; micro-sensor and computational fluid dynamics simulations
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Guest Editor
Department of BioNano Technology, Gachon University, Gyeonggi 13120, Republic of Korea
Interests: nano-biosensor; biosynthesis of drug candiates & drug delivery; cell-based biosensors & anti-bacterial assay; in vitro biosynthesis of nanoparticles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Paper-based biosensors, with the inherent merits of paper cellulose (e.g., low cost, abundant reserves, facilitated functionalization, green biodegradation) have attracted considerable attention in the operation of point-of-care diagnostics. By integrating the multiplex capabilities of relatively well-developed microfluidics with the flexibility and simplicity of lateral flow test strip technology, paper-based biosensors represent a new generation of point-of-care diagnostic methods, especially in the areas where resources are limited. So far, the development of this technology has brought significant improvements, and a variety of novel paper-based biosensors have emerged to provide powerful analytical strategies for the development of affordable, portable, low-cost technologies in the fields of clinical diagnosis; they are now essential for the treatment and management of infectious diseases. Paper-based biosensors can be classified into microfluidic biosensors, dipstick tests, and lateral flow assays, which allow all the detection of proteins, amino acids, nucleic acids, bacteria and pathogens, lending them great potential to launch a revolution in disease diagnostics. Accordingly, this Special Issue seeks to showcase research papers, short communications, and review articles that focus on state-of-the-art developments and applications of paper-based biosensors including (but not limited to) fabrication, modeling, sample pretreatment, and novel detection methodologies.

Dr. Kang Cui
Prof. Dr. Lung-Ming Fu
Dr. Moon Il Kim
Guest Editors

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Keywords

  • paper-based biosensor
  • paper-based analytical device
  • lab-on-paper
  • point-of-care device
  • dipstick test
  • lateral flow assays
  • microfluidics biosensor

Published Papers (13 papers)

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Research

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13 pages, 1172 KiB  
Article
Engineering At-Home Dilution and Filtration Methods to Enable Paper-Based Colorimetric Biosensing in Human Blood with Cell-Free Protein Synthesis
by Tyler J. Free, Ryan W. Tucker, Katelyn M. Simonson, Sydney A. Smith, Caleb M. Lindgren, William G. Pitt and Bradley C. Bundy
Biosensors 2023, 13(1), 104; https://doi.org/10.3390/bios13010104 - 06 Jan 2023
Cited by 3 | Viewed by 2782
Abstract
Diagnostic blood tests can guide the administration of healthcare to save and improve lives. Most clinical biosensing blood tests require a trained technician and specialized equipment to process samples and interpret results, which greatly limits test accessibility. Colorimetric paper-based diagnostics have an equipment-free [...] Read more.
Diagnostic blood tests can guide the administration of healthcare to save and improve lives. Most clinical biosensing blood tests require a trained technician and specialized equipment to process samples and interpret results, which greatly limits test accessibility. Colorimetric paper-based diagnostics have an equipment-free readout, but raw blood obscures a colorimetric response which has motivated diverse efforts to develop blood sample processing techniques. This work uses inexpensive readily-available materials to engineer user-friendly dilution and filtration methods for blood sample collection and processing to enable a proof-of-concept colorimetric biosensor that is responsive to glutamine in 50 µL blood drop samples in less than 30 min. Paper-based user-friendly blood sample collection and processing combined with CFPS biosensing technology represents important progress towards the development of at-home biosensors that could be broadly applicable to personalized healthcare. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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15 pages, 3210 KiB  
Article
PEC/Colorimetric Dual-Mode Lab-on-Paper Device via BiVO4/FeOOH Nanocomposite In Situ Modification on Paper Fibers for Sensitive CEA Detection
by Xu Li, Jiali Huang, Jiayu Ding, Mingzhen Xiu, Kang Huang, Kang Cui, Jing Zhang, Shiji Hao, Yan Zhang, Jinghua Yu and Yizhong Huang
Biosensors 2023, 13(1), 103; https://doi.org/10.3390/bios13010103 - 06 Jan 2023
Cited by 2 | Viewed by 2098
Abstract
A dual-mode lab-on-paper device based on BiVO4/FeOOH nanocomposites as an efficient generating photoelectrochemical (PEC)/colorimetric signal reporter has been successfully constructed by integration of the lab-on-paper sensing platform and PEC/colorimetric detection technologies for sensitive detection of carcinoembryonic antigen (CEA). Concretely, the BiVO [...] Read more.
A dual-mode lab-on-paper device based on BiVO4/FeOOH nanocomposites as an efficient generating photoelectrochemical (PEC)/colorimetric signal reporter has been successfully constructed by integration of the lab-on-paper sensing platform and PEC/colorimetric detection technologies for sensitive detection of carcinoembryonic antigen (CEA). Concretely, the BiVO4/FeOOH nanocomposites were in situ synthesized onto the paper-working electrode (PWE) through hydrothermal synthesis of the BiVO4 layer on cellulose fibers (paper-based BiVO4) which were initially modified by Au nanoparticles for improving the conductivity of three dimensional PWE, and then the photo-electrodeposition of FeOOH onto the paper-based BiVO4 to construct the paper-based BiVO4/FeOOH for the portable dual-mode lab-on-paper device. The obtained nanocomposites with an FeOOH needle-like structure deposited on the BiVO4 layer exhibits enhanced PEC response activity due to its effective separation of the electron–hole pair which could further accelerate the PEC conversion efficiency during the sensing process. With the introduction of CEA targets onto the surface of nanocomposite-modified PWE assisted by the interaction with the CEA antibody from a specific recognition property, a signal-off PEC signal state with a remarkable photocurrent response decreasing trend can be achieved, realizing the quantitative detection of CEA with the PEC signal readout mode. By means of a smart origami paper folding, the colorimetric signal readout is achieved by catalyzing 3,3′,5,5′-tetramethylbenzidine (TMB) to generate blue oxidized TMB in the presence of H2O2 due to the satisfied enzyme-like catalytic activity of the needle-like structure, FeOOH, thereby achieving the dual-mode signal readout system for the proposed lab-on-paper device. Under the optimal conditions, the PEC and colorimetric signals measurement were effectively carried out, and the corresponding linear ranges were 0.001–200 ng·mL−1 and 0.5–100 ng·mL−1 separately, with the limit of detection of 0.0008 and 0.013 ng·mL−1 for each dual-mode. The prepared lab-on-paper device also presented a successful application in serum samples for the detection of CEA, providing a potential pathway for the sensitive detection of target biomarkers in clinical application. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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24 pages, 10677 KiB  
Article
Complete Breast Cancer Detection and Monitoring System by Using Microwave Textile Based Antenna Sensors
by Dalia N. Elsheakh, Rawda A. Mohamed, Omar M. Fahmy, Khaled Ezzat and Angie R. Eldamak
Biosensors 2023, 13(1), 87; https://doi.org/10.3390/bios13010087 - 04 Jan 2023
Cited by 19 | Viewed by 5238
Abstract
This paper presents the development of a new complete wearable system for detecting breast tumors based on fully textile antenna-based sensors. The proposed sensor is compact and fully made of textiles so that it fits conformably and comfortably on the breasts with dimensions [...] Read more.
This paper presents the development of a new complete wearable system for detecting breast tumors based on fully textile antenna-based sensors. The proposed sensor is compact and fully made of textiles so that it fits conformably and comfortably on the breasts with dimensions of 24 × 45 × 0.17 mm3 on a cotton substrate. The proposed antenna sensor is fed with a coplanar waveguide feed for easy integration with other systems. It realizes impedance bandwidth from 1.6 GHz up to 10 GHz at |S11| ≤ −6 dB (VSWR ≤ 3) and from 1.8 to 2.4 GHz and from 4 up to 10 GHz at |S11| ≤ −10 dB (VSWR ≤ 2). The proposed sensor acquires a low specific absorption rate (SAR) of 0.55 W/kg and 0.25 W/kg at 1g and 10 g, respectively, at 25 dBm power level over the operating band. Furthermore, the proposed system utilizes machine-learning algorithms (MLA) to differentiate between malignant tumor and benign breast tissues. Simulation examples have been recorded to verify and validate machine-learning algorithms in detecting tumors at different sizes of 10 mm and 20 mm, respectively. The classification accuracy reached 100% on the tested dataset when considering |S21| parameter features. The proposed system is vision as a “Smart Bra” that is capable of providing an easy interface for women who require continuous breast monitoring in the comfort of their homes. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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12 pages, 2368 KiB  
Article
Hollow-Channel Paper Analytical Devices Supported Biofuel Cell-Based Self-Powered Molecularly Imprinted Polymer Sensor for Pesticide Detection
by Yanhu Wang, Huihui Shi, Jiantao Sun, Jianjian Xu, Mengchun Yang and Jinghua Yu
Biosensors 2022, 12(11), 974; https://doi.org/10.3390/bios12110974 - 05 Nov 2022
Cited by 4 | Viewed by 1596
Abstract
Herein, a paper-based glucose/air biofuel cell (BFC) was constructed and implemented for self-powered pesticide detection. Our developed paper-based chip relies on a hollow-channel to transport fluids rather than capillarity, which reduces analysis times as well as physical absorption. The gold nanoparticles (Au NPs) [...] Read more.
Herein, a paper-based glucose/air biofuel cell (BFC) was constructed and implemented for self-powered pesticide detection. Our developed paper-based chip relies on a hollow-channel to transport fluids rather than capillarity, which reduces analysis times as well as physical absorption. The gold nanoparticles (Au NPs) and carbon nanotubes (CNTs) were adapted to modify the paper fibers to fabricate the flexible conductive paper anode/cathode electrode (Au–PAE/CNT–PCE). Molecularly imprinted polymers (MIPs) using 2,4-dichlorophenoxyacetic acid (2,4-D) as a template were synthesized on Au–PAE for signal control. In the cathode, bilirubin oxidase (BOD) was used for the oxygen reduction reaction. Based on a competitive reaction between 2,4-D and glucose-oxidase-labeled 2,4-D (GOx-2,4-D), the amount of GOx immobilized on the bioanode can be simply tailored, thus a signal-off self-powered sensing platform was achieved for 2,4-D determination. Meanwhile, the coupling of the paper supercapacitor (PS) with the paper-based chip provides a simple route for signal amplification. Combined with a portable digital multi-meter detector, the amplified signal can be sensitively readout. Through rational design of the paper analytical device, the combination of BFC and PS provides a new prototype for constructing a low-cost, simple, portable, and sensitive self-powered biosensor lab-on-paper, which could be easily expanded in the field of clinical analysis and drug delivery. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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13 pages, 4305 KiB  
Article
A Paper-Based Electrochemical Sensor Based on PtNP/COFTFPB−DHzDS@rGO for Sensitive Detection of Furazolidone
by Rongfang Chen, Xia Peng, Yonghai Song and Yan Du
Biosensors 2022, 12(10), 904; https://doi.org/10.3390/bios12100904 - 21 Oct 2022
Cited by 8 | Viewed by 1615
Abstract
Herein, a paper-based electrochemical sensor based on PtNP/COFTFPB−DHzDS@rGO was developed for the sensitive detection of furazolidone. A cluster-like covalent organic framework (COFTFPB−DHzDS) was successfully grown on the surface of amino-functional reduced graphene oxide (rGO-NH2) to avoid serious [...] Read more.
Herein, a paper-based electrochemical sensor based on PtNP/COFTFPB−DHzDS@rGO was developed for the sensitive detection of furazolidone. A cluster-like covalent organic framework (COFTFPB−DHzDS) was successfully grown on the surface of amino-functional reduced graphene oxide (rGO-NH2) to avoid serious self-aggregation, which was further loaded with platinum nanoparticles (PtNPs) with high catalytic activity as nanozyme to obtain PtNP/COFTFPB−DHzDS@rGO nanocomposites. The morphology of PtNP/COFTFPB−DHzDS@rGO nanocomposites was characterized, and the results showed that the smooth rGO surface became extremely rough after the modification of COFTFPB−DHzDS. Meanwhile, ultra-small PtNPs with sizes of around 1 nm were precisely anchored on COFTFPB−DHzDS to maintain their excellent catalytic activity. The conventional electrodes were used to detect furazolidone and showed a detection limit as low as 5 nM and a linear range from 15 nM to 110 μM. In contrast, the detection limit for the paper-based electrode was 0.23 μM, and the linear range was 0.69–110 μM. The results showed that the paper-based electrode can be used to detect furazolidone. This sensor is a potential candidate for the detection of furazolidone residue in human serum and fish samples. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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13 pages, 3417 KiB  
Article
A Novel Paper-Based Electrochemical Biosensor Based on N,O-Rich Covalent Organic Frameworks for Carbaryl Detection
by Yawen Xiao, Na Wu, Li Wang and Lili Chen
Biosensors 2022, 12(10), 899; https://doi.org/10.3390/bios12100899 - 20 Oct 2022
Cited by 9 | Viewed by 1773
Abstract
A new N,O-rich covalent organic framework (COFDHNDA-BTH) was synthesized by an amine-aldehyde condensation reaction between 2,6-dialdehyde-1,5-dihydroxynaphthalene (DHNDA) and 1,3,5-phenyltriformylhydrazine (BTH) for carbaryl detection. The free NH, OH, and C=O groups of COFDHNDA-BTH not only covalently couples with acetylcholinesterase (AChE) into [...] Read more.
A new N,O-rich covalent organic framework (COFDHNDA-BTH) was synthesized by an amine-aldehyde condensation reaction between 2,6-dialdehyde-1,5-dihydroxynaphthalene (DHNDA) and 1,3,5-phenyltriformylhydrazine (BTH) for carbaryl detection. The free NH, OH, and C=O groups of COFDHNDA-BTH not only covalently couples with acetylcholinesterase (AChE) into the pores of COFDHNDA-BTH, but also greatly improves the catalytic activity of AChE in the constrained environment of COFDHNDA-BTH’s pore. Under the catalysis of AChE, the acetylthiocholine (ATCl) was decomposed into positively charged thiocholine (TCl), which was captured on the COFDHNDA-BTH modified electrode. The positive charges of TCl can attract anionic probe [Fe(CN)6]3−/4− on the COFDHNDA-BTH-modified electrode to show a good oxidation peak at 0.25 V (versus a saturated calomel electrode). The carbaryl detection can inhibit the activity of AChE, resulting in the decrease in the oxidation peak. Therefore, a turn-off electrochemical carbaryl biosensor based on a flexible carbon paper electrode loaded with COFDHNDA-BTH and AChE was constructed using the oxidation peak of an anionic probe [Fe(CN)6]3−/4− as the detection signal. The detection limit was 0.16 μM (S/N = 3), and the linear range was 0.48~35.0 μM. The sensor has good selectivity, repeatability, and stability, and has a good application prospect in pesticide detection. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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15 pages, 2789 KiB  
Article
A Paper-Based Analytical Device Integrated with Smartphone: Fluorescent and Colorimetric Dual-Mode Detection of β-Glucosidase Activity
by Wei-Yi Zhang, Tao Tian, Li-Jing Peng, Hang-Yu Zhou, Hao Zhang, Hua Chen and Feng-Qing Yang
Biosensors 2022, 12(10), 893; https://doi.org/10.3390/bios12100893 - 18 Oct 2022
Cited by 13 | Viewed by 2448
Abstract
In this work, indoxyl-glucoside was used as the substrate to develop a cost-effective, paper-based analytical device for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity through a smartphone. The β-glucosidase can hydrolyze the colorless substrate indoxyl-glucoside to release indoxyl, which will be [...] Read more.
In this work, indoxyl-glucoside was used as the substrate to develop a cost-effective, paper-based analytical device for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity through a smartphone. The β-glucosidase can hydrolyze the colorless substrate indoxyl-glucoside to release indoxyl, which will be self-oxidized to generate green products in the presence of oxygen. Meanwhile, the green products emit bright blue-green fluorescence under ultraviolet–visible light irradiation at 365 nm. Fluorescent or colorimetric images were obtained by a smartphone, and the red-green-blue channels were analyzed by the Adobe Photoshop to quantify the β-glucosidase activity. Under the optimum conditions, the relative fluorescent and colorimetric signals have a good linear relationship with the activity of β-glucosidase, in the range of 0.01–1.00 U/mL and 0.25–5.00 U/mL, and the limits of detection are 0.005 U/mL and 0.0668 U/mL, respectively. The activities of β-glucosidase in a crude almond sample measured by the fluorescent and colorimetric methods were 23.62 ± 0.53 U/mL and 23.86 ± 0.25 U/mL, respectively. In addition, the spiked recoveries of normal human serum and crude almond samples were between 87.5% and 118.0%. In short, the paper-based device, combined with a smartphone, can provide a simple, environmentally friendly, and low-cost method for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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17 pages, 3915 KiB  
Article
A Paper-Based Photoelectrochemical Sensing Platform Based on In Situ Grown ZnO/ZnIn2S4 Heterojunctions onto Paper Fibers for Sensitively Detecting AFP
by Jiali Huang, Xu Li, Mingzhen Xiu, Kang Huang, Kang Cui, Jing Zhang, Shenguang Ge, Shiji Hao, Jinghua Yu and Yizhong Huang
Biosensors 2022, 12(10), 818; https://doi.org/10.3390/bios12100818 - 02 Oct 2022
Cited by 8 | Viewed by 2252
Abstract
Nowadays, developing a cost-effective, easy-to-operate, and efficient signal amplification platform is of important to microfluidic paper-based analytical devices (μPAD) for end-use markets of point-of-care (POC) assay applications. Herein, an ultrasensitive, paper-based photoelectrochemical (PEC) bioassay platform is constructed by in situ grown [...] Read more.
Nowadays, developing a cost-effective, easy-to-operate, and efficient signal amplification platform is of important to microfluidic paper-based analytical devices (μPAD) for end-use markets of point-of-care (POC) assay applications. Herein, an ultrasensitive, paper-based photoelectrochemical (PEC) bioassay platform is constructed by in situ grown ZnO/ZnIn2S4 heterojunctions onto paper fibers, which acted as photoactive signal amplification probes for enhancing the sensitivity of antibodies-based diagnostic assays, for the sensitive detection of alpha-fetoprotein (AFP) targets. The crystalline flake-like ZnIn2S4 composited with hexagonal nanorods (NRs) morphology of ZnO is an in situ grown, at the first time, onto cellulose fibers surface supported with Au nanoparticle (Au NP) modification to improve conductivity of the device working zone. The obtained composites on paper fibers are implemented as a flexible paper-based photoelectrode to realize remarkable performance of the fabricated μPAD, resulting from the enhanced PEC activity of heterojunctions with effective electron-hole pair separation for accelerating photoelectric conversion efficiency of the sensing process under light irradiation. Once the target AFP was introduced into the biosensing interface assistant, with a specific recognition interaction of AFP antibody, a drastically photocurrent response was generated, in view of the apparent steric effects. With the concentration increase of AFP targets, more immune conjugates could be confined onto the biosensing interface, eventually leading to the quantitative decrease of photocurrent intensity. Combined with an ingenious origami design and permitting the hydrophobic/hydrophilic conversion procedure in the bioassay process, the ultrasensitive PEC detection of AFP targets was realized. Under the optimized conditions, the level of AFP could be sensitively tracked by the prepared μPAD with a liner range from 0.1 to 100 ng mL−1 and limit of detection of 0.03 ng mL−1. This work provides a great potential application for highly selective and sensitive POC testing of AFP, and finally, developments for clinical disease diagnosis. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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15 pages, 3318 KiB  
Article
Ultra-Sensitive and Semi-Quantitative Vertical Flow Assay for the Rapid Detection of Interleukin-6 in Inflammatory Diseases
by Rongwei Lei, Hufsa Arain, Maryam Obaid, Nivriti Sabhnani and Chandra Mohan
Biosensors 2022, 12(9), 756; https://doi.org/10.3390/bios12090756 - 14 Sep 2022
Cited by 4 | Viewed by 2371
Abstract
The inflammation biomarker Interleukin 6 (IL-6) exhibits a concentration of less than 7 pg/mL in healthy serum but increases 10–100-fold when inflammation occurs. Increased serum IL-6 has been reported in chronic diseases such as rheumatoid arthritis (RA), as well as in life-threatening acute [...] Read more.
The inflammation biomarker Interleukin 6 (IL-6) exhibits a concentration of less than 7 pg/mL in healthy serum but increases 10–100-fold when inflammation occurs. Increased serum IL-6 has been reported in chronic diseases such as rheumatoid arthritis (RA), as well as in life-threatening acute illnesses such as sepsis and cytokine release syndrome (CRS). This work seeks to meet the demand for rapid detection of serum IL-6 both for rapid monitoring of chronic diseases and for triaging patients with acute illnesses. Following the optimization of several types of gold nanoparticles, membrane pore sizes, and buffer systems, an ultra-sensitive vertical flow assay (VFA) was engineered, allowing the detection of recombinant IL-6 in spiked buffer with a limit of detection (LoD) of 10 pg/mL and a reportable range of 10–10,000 pg/mL with a 15-min assay time. The detection of IL-6 in spiked pooled healthy serum exhibited an LoD of 3.2 pg/mL and a reportable range of 10–10,000 pg/mL. The VFA’s stability was demonstrated over 1-day, two-week, four-week, and six-week storage durations at room temperature. The inter-operator CV and intra-operator CV were determined to be 14.3% and 15.2%, respectively. Three reference zones, high, low, and blank, were introduced into the cartridge to facilitate on-site semi-quantitative measurements across a 6-point semi-quantitative range. Finally, the performance of the IL-6 VFA was validated using 20 RA and 20 healthy control (HC) clinical serum samples, using ELISA as the gold standard platform. The ultra-sensitive, rapid IL-6 VFA could potentially be used to triage patients for intensive care, treatment adjustments, or for monitoring disease activity in inflammatory conditions. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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13 pages, 2165 KiB  
Article
Magnetic Bead Handling Using a Paper-Based Device for Quantitative Point-of-Care Testing
by Kevin Arias-Alpízar, Ana Sánchez-Cano, Judit Prat-Trunas, Elena Sulleiro, Pau Bosch-Nicolau, Fernando Salvador, Inés Oliveira, Israel Molina, Adrián Sánchez-Montalvá and Eva Baldrich
Biosensors 2022, 12(9), 680; https://doi.org/10.3390/bios12090680 - 25 Aug 2022
Cited by 1 | Viewed by 1839
Abstract
Microfluidic paper-based analytical devices (μPADs) have been extensively proposed as ideal tools for point-of-care (POC) testing with minimal user training and technical requirements. However, most μPADs use dried bioreagents, which complicate production, reduce device reproducibility and stability, and require transport and storage under [...] Read more.
Microfluidic paper-based analytical devices (μPADs) have been extensively proposed as ideal tools for point-of-care (POC) testing with minimal user training and technical requirements. However, most μPADs use dried bioreagents, which complicate production, reduce device reproducibility and stability, and require transport and storage under temperature and humidity-controlled conditions. In this work, we propose a μPAD produced using an affordable craft-cutter and stored at room temperature, which is used to partially automate a single-step colorimetric magneto-immunoassay. As a proof-of-concept, the μPAD has been applied to the quantitative detection of Plasmodium falciparum lactate dehydrogenase (Pf-LDH), a biomarker of malaria infection. In this system, detection is based on a single-step magneto-immunoassay that consists of a single 5-min incubation of the lysed blood sample with immuno-modified magnetic beads (MB), detection antibody, and an enzymatic signal amplifier (Poly-HRP). This mixture is then transferred to a single-piece paper device where, after on-chip MB magnetic concentration and washing, signal generation is achieved by adding a chromogenic enzyme substrate. The colorimetric readout is achieved by the naked eye or using a smartphone camera and free software for image analysis. This μPAD afforded quantitative Pf-LDH detection in <15 min, with a detection limit of 6.25 ng mL−1 when the result was interpreted by the naked eye and 1.4 ng mL−1 when analysed using the smartphone imaging system. Moreover, the study of a battery of clinical samples revealed concentrations of Pf-LDH that correlated with those provided by the reference ELISA and with better sensitivity than a commercial rapid diagnostic test (RDT). These results demonstrate that magneto-immunoassays can be partly automated by employing a μPAD, achieving a level of handling that approaches the requirements of POC testing. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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13 pages, 2463 KiB  
Article
Microfluidic Sliding Paper-Based Device for Point-of-Care Determination of Albumin-to-Creatine Ratio in Human Urine
by Szu-Jui Chen, Chin-Chung Tseng, Kuan-Hsun Huang, Yu-Chi Chang and Lung-Ming Fu
Biosensors 2022, 12(7), 496; https://doi.org/10.3390/bios12070496 - 07 Jul 2022
Cited by 6 | Viewed by 3130
Abstract
A novel assay platform consisting of a microfluidic sliding double-track paper-based chip and a hand-held Raspberry Pi detection system is proposed for determining the albumin-to-creatine ratio (ACR) in human urine. It is a clinically important parameter and can be used for the early [...] Read more.
A novel assay platform consisting of a microfluidic sliding double-track paper-based chip and a hand-held Raspberry Pi detection system is proposed for determining the albumin-to-creatine ratio (ACR) in human urine. It is a clinically important parameter and can be used for the early detection of related diseases, such as renal insufficiency. In the proposed method, the sliding layer of the microchip is applied and the sample diffuses through two parallel filtration channels to the reaction/detection areas of the microchip to complete the detection reaction, which is a simple method well suited for self-diagnosis of ACR index in human urine. The RGB (red, green, and blue) value intensity signals of the reaction complexes in these two reaction zones are analyzed by a Raspberry Pi computer to derive the ACR value (ALB and CRE concentrations). It is shown that the G + B value intensity signal is linearly related to the ALB and CRE concentrations with the correlation coefficients of R2 = 0.9919 and R2 = 0.9923, respectively. It is additionally shown that the ALB and CRE concentration results determined using the proposed method for 23 urine samples were collected from real suffering chronic kidney disease (CKD) patients are in fine agreement with those acquired operating a traditional high-reliability macroscale method. Overall, for point-of-care (POC) CKD diagnosis and monitoring in clinical applications, the results prove that the proposed method offers a convenient, real time, reliable, and low-spending solution for POC CKD diagnosis. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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Review

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34 pages, 836 KiB  
Review
Application of Paper-Based Microfluidic Analytical Devices (µPAD) in Forensic and Clinical Toxicology: A Review
by Giacomo Musile, Cristian Grazioli, Stefano Fornasaro, Nicolò Dossi, Elio Franco De Palo, Franco Tagliaro and Federica Bortolotti
Biosensors 2023, 13(7), 743; https://doi.org/10.3390/bios13070743 - 18 Jul 2023
Cited by 5 | Viewed by 4023
Abstract
The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent [...] Read more.
The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent years, the technology of paper-based microfluidic analytical devices (μPADs) has undergone rapid development and now provides a feasible, low-cost alternative to traditional rapid tests for detecting harmful compounds. In fact, µPADs have been developed to detect toxic molecules (arsenic, cyanide, ethanol, and nitrite), drugs, and drugs of abuse (benzodiazepines, cathinones, cocaine, fentanyl, ketamine, MDMA, morphine, synthetic cannabinoids, tetrahydrocannabinol, and xylazine), and also psychoactive substances used for drug-facilitated crimes (flunitrazepam, gamma-hydroxybutyric acid (GHB), ketamine, metamizole, midazolam, and scopolamine). The present report critically evaluates the recent developments in paper-based devices, particularly in detection methods, and how these new analytical tools have been tested in forensic and clinical toxicology, also including future perspectives on their application, such as multisensing paper-based devices, microfluidic paper-based separation, and wearable paper-based sensors. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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22 pages, 2844 KiB  
Review
Review on the Selection of Aptamers and Application in Paper-Based Sensors
by Kaifei Wang, Minglu Wang, Teng Ma, Wenyu Li and Hongyan Zhang
Biosensors 2023, 13(1), 39; https://doi.org/10.3390/bios13010039 - 27 Dec 2022
Cited by 11 | Viewed by 3447
Abstract
An aptamer is a synthetic oligonucleotide, referring to a single-stranded deoxyribonucleic acid or ribonucleic acid ligand produced by synthesis from outside the body using systematic evolution of ligands by exponential enrichment (SELEX) technology. Owing to their special screening process and adjustable tertiary structures, [...] Read more.
An aptamer is a synthetic oligonucleotide, referring to a single-stranded deoxyribonucleic acid or ribonucleic acid ligand produced by synthesis from outside the body using systematic evolution of ligands by exponential enrichment (SELEX) technology. Owing to their special screening process and adjustable tertiary structures, aptamers can bind to multiple targets (small molecules, proteins, and even whole cells) with high specificity and affinity. Moreover, due to their simple preparation and stable modification, they have been widely used to construct biosensors for target detection. The paper-based sensor is a product with a low price, short detection time, simple operation, and other superior characteristics, and is widely used as a rapid detection method. This review mainly focuses on the screening methods of aptamers, paper-based devices, and applicable sensing strategies. Furthermore, the design of the aptamer-based lateral flow assay (LFA), which underlies the most promising devices for commercialization, is emphasized. In addition, the development prospects and potential applications of paper-based biosensors using aptamers as recognition molecules are also discussed. Full article
(This article belongs to the Special Issue Paper-Based Biosensors)
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