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Portable Biosensing Systems for Point-of-Care Diagnostic Applications

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

Deadline for manuscript submissions: closed (31 March 2019) | Viewed by 75084

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Special Issue Editors

Prof. Themis Prodromakis

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Guest Editor

University of Southampton
Interests: biomedical devices; biosignal processing; nanotechnology; bioelectronics

Dr. Konstantinos I. Papadimitriou

E-Mail Website
Guest Editor

University College London
Interests: bioelectronics; microelectronics; FPGAs; medical devices; medical imaging

Special Issue Information

Dear Colleagues,

The field of bioanalytical and point-of-care diagnostic platforms is constantly changing and evolving, taking advantage of developments in biosensing technologies, materials and technology innovations. Modern healthcare systems rely more on interfacing to our digital world, contributing to the trend of the Internet of Things, and more generally providing the long sought-after rapid and efficient monitoring and detection of various diseases. The major challenge for Point-of-Care diagnostics still lies in complying with the ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Robust and Rapid, Equipment-free and Deliverable to end-users), as defined by the World Health Organization.

This Special Issue aims showcasing several point-of-care diagnostic solutions, covering a broad range of techniques, materials and methods employed to satisfy the ASSURED criteria. We wish to cover research works that focus on either a full Point-of-Care solution (e.g., lab-on-chip) or innovative parts of it (e.g., microfluidics, sample preparation units, control/detection/processing electronics) that mainly demonstrate diagnostic accuracy and clinical value for individuals and healthcare systems.

Prof. Themis Prodromakis
Dr. Konstantinos I. Papadimitriou
Guest Editors

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Keywords

Point-of-care diagnostics
CMOS sensors/circuitry for point-of-care
Optical technologies for point-of-care
Paper-based analytical devices
Smartphone-based point-of-care devices
Biomedical circuits and systems
Bioelectronic devices
Biosensors
Integrated sensors
Internet-of-Things / Wearable devices
Lab-on-Chip
Microfluidics

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Published Papers (11 papers)

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Research

13 pages, 4759 KiB

Open AccessArticle

A Low-Cost Time-Correlated Single Photon Counting Portable DNA Analyzer

by Yi Tian, Liping Wei and Derek Ho

Sensors 2019, 19(13), 2838; https://doi.org/10.3390/s19132838 - 26 Jun 2019

Cited by 4 | Viewed by 3799

Abstract

Photon-counting analysis of nucleic acids plays a key role in many diagnostics applications for its accurate and non-invasive nature. However, conventional photon-counting instrumentations are bulky and expensive due to the use of conventional optics and a lack of optimization of electronics. In this paper, we present a portable, low-cost time-correlated single photon-counting (TCSPC) analysis system for DNA detection. Both optical and electronic subsystems are carefully designed to provide effective emission filtering and size reduction, delivering good DNA detection and fluorescence lifetime extraction performance. DNA detection has been verified by fluorescence lifetime measurements of a V-carbazole conjugated fluorophore lifetime bioassay. The time-to-digital module of the proposed TCSPC system achieves a full width at half maximum (FWHM) timing resolution from 121 to 145 ps and a differential non-linearity (DNL) between −8.5% and +9.7% of the least significant bit (LSB) within the 500 ns full-scale range (FSR). With a detection limit of 6.25 nM and a dynamic range of 6.8 ns, the proposed TCSPC system demonstrates the enabling technology for rapid, point-of-care DNA diagnostics. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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12 pages, 3758 KiB

Open AccessArticle

Handheld Microflow Cytometer Based on a Motorized Smart Pipette, a Microfluidic Cell Concentrator, and a Miniaturized Fluorescence Microscope

by Byeongyeon Kim, Dayoung Kang and Sungyoung Choi

Sensors 2019, 19(12), 2761; https://doi.org/10.3390/s19122761 - 19 Jun 2019

Cited by 9 | Viewed by 4900

Abstract

Miniaturizing flow cytometry requires a comprehensive approach to redesigning the conventional fluidic and optical systems to have a small footprint and simple usage and to enable rapid cell analysis. Microfluidic methods have addressed some challenges in limiting the realization of microflow cytometry, but most microfluidics-based flow cytometry techniques still rely on bulky equipment (e.g., high-precision syringe pumps and bench-top microscopes). Here, we describe a comprehensive approach that achieves high-throughput white blood cell (WBC) counting in a portable and handheld manner, thereby allowing the complete miniaturization of flow cytometry. Our approach integrates three major components: a motorized smart pipette for accurate volume metering and controllable liquid pumping, a microfluidic cell concentrator for target cell enrichment, and a miniaturized fluorescence microscope for portable flow cytometric analysis. We first validated the capability of each component by precisely metering various fluid samples and controlling flow rates in a range from 219.5 to 840.5 μL/min, achieving high sample-volume reduction via on-chip WBC enrichment, and successfully counting single WBCs flowing through a region of interrogation. We synergistically combined the three major components to create a handheld, integrated microflow cytometer and operated it with a simple protocol of drawing up a blood sample via pipetting and injecting the sample into the microfluidic concentrator by powering the motorized smart pipette. We then demonstrated the utility of the microflow cytometer as a quality control means for leukoreduced blood products, quantitatively analyzing residual WBCs (rWBCs) in blood samples present at concentrations as low as 0.1 rWBCs/μL. These portable, controllable, high-throughput, and quantitative microflow cytometric technologies provide promising ways of miniaturizing flow cytometry. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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19 pages, 2212 KiB

Open AccessArticle

A Clinically Evaluated Interferometric Continuous-Wave Radar System for the Contactless Measurement of Human Vital Parameters

by Fabian Michler, Kilin Shi, Sven Schellenberger, Tobias Steigleder, Anke Malessa, Laura Hameyer, Nina Neumann, Fabian Lurz, Christoph Ostgathe, Robert Weigel and Alexander Koelpin

Sensors 2019, 19(11), 2492; https://doi.org/10.3390/s19112492 - 31 May 2019

Cited by 32 | Viewed by 6202

Abstract

Vital parameters are key indicators for the assessment of health. Conventional methods rely on direct contact with the patients’ skin and can hence cause discomfort and reduce autonomy. This article presents a bistatic 24 GHz radar system based on an interferometric six-port architecture and features a precision of 1 µm in distance measurements. Placed at a distance of 40 cm in front of the human chest, it detects vibrations containing respiratory movements, pulse waves and heart sounds. For the extraction of the respiration rate, time-domain approaches like autocorrelation, peaksearch and zero crossing rate are compared to the Fourier transform, while template matching and a hidden semi-Markov model are utilized for the detection of the heart rate from sphygmograms and heart sounds. A medical study with 30 healthy volunteers was conducted to collect 5.5 h of data, where impedance cardiogram and electrocardiogram were used as gold standard for synchronously recording respiration and heart rate, respectively. A low root mean square error for the breathing rate (0.828 BrPM) and a high overall F1 score for heartbeat detection (93.14%) could be achieved using the proposed radar system and signal processing. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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14 pages, 3014 KiB

Open AccessArticle

Robust Smartphone Assisted Biosensing Based on Asymmetric Nanofluidic Grating Interferometry

by Foelke Purr, Max-Frederik Eckardt, Jonas Kieserling, Paul-Luis Gronwald, Thomas P. Burg and Andreas Dietzel

Sensors 2019, 19(9), 2065; https://doi.org/10.3390/s19092065 - 3 May 2019

Cited by 7 | Viewed by 3752

Abstract

Point-of-care systems enable fast therapy decisions on site without the need of any healthcare infrastructure. In addition to the sensitive detection, stable measurement by inexperienced persons outside of laboratory facilities is indispensable. A particular challenge in field applications is to reduce interference from environmental factors, such as temperature, to acceptable levels without sacrificing simplicity. Here, we present a smartphone-based point-of-care sensor. The method uses an optofluidic grating composed of alternating detection and reference channels arranged as a reflective phase grating. Biomolecules adsorbing to the detection channel alter the optical path length, while the parallel reference channels enable a direct common mode rejection within a single measurement. The optical setup is integrated in a compact design of a mobile readout device and the usability is ensured by a smartphone application. Our results show that different ambient temperatures do not have any influence on the signal. In a proof-of concept experiment we measured the accumulation of specific molecules in functionalized detection channels in real-time and without the need of any labeling. Therefore, the channel walls have been modified with biotin as capture molecules and the specific binding of streptavidin was detected. A mobile, reliable and robust point-of-care device has been realized by combining an inherently differential measurement concept with a smartphone-based, mobile readout device. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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14 pages, 4800 KiB

Open AccessArticle

A Novel Wearable EEG and ECG Recording System for Stress Assessment

by Joong Woo Ahn, Yunseo Ku and Hee Chan Kim

Sensors 2019, 19(9), 1991; https://doi.org/10.3390/s19091991 - 28 Apr 2019

Cited by 128 | Viewed by 16068

Abstract

Suffering from continuous stress can lead to serious psychological and even physical disorders. Objective stress assessment methods using noninvasive physiological responses such as heart rate variability (HRV) and electroencephalograms (EEG) have therefore been proposed for effective stress management. In this study, a novel wearable device that can measure electrocardiograms (ECG) and EEG simultaneously was designed to enable continuous stress monitoring in daily life. The developed system is easily worn by hanging from both ears, is lightweight (i.e., 42.5 g), and exhibits an excellent noise performance of 0.12 μVrms. Significant time and frequency features of HRV and EEG were found in two different stressors, namely the Stroop color word and mental arithmetic tests, using 14 young subjects. Stressor situations were classified using various HRV and EEG feature selections and a support vector machine technique. The five-fold cross-validation results obtained when using both EEG and HRV features showed the best performance with an accuracy of 87.5%, which demonstrated the requirement for simultaneous HRV and EEG measurements. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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23 pages, 64210 KiB

Open AccessArticle

INBED: A Highly Specialized System for Bed-Exit-Detection and Fall Prevention on a Geriatric Ward

by Nico Jähne-Raden, Ulf Kulau, Michael Marschollek and Klaus-Hendrik Wolf

Sensors 2019, 19(5), 1017; https://doi.org/10.3390/s19051017 - 27 Feb 2019

Cited by 20 | Viewed by 9962

Abstract

Objective: In geriatric institutions, the risk of falling of patients is very high and frequently leads to fractures of the femoral neck, which can result in serious consequences and medical costs. With regard to the current numbers of elderly people, the need for smart solutions for the prevention of falls in clinical environments as well as in everyday life has been evolving. Methods: Hence, in this paper, we present the Inexpensive Node for bed-exit Detection (INBED), a comprehensive, favourable signaling system for bed-exit detection and fall prevention, to support the clinical efforts in terms of fall reduction. The tough requirements for such a system in clinical environments were gathered in close cooperation with geriatricians. Results: The conceptional efforts led to a multi-component system with a core wearable device, attached to the patients, to detect several types of movements such as rising, restlessness and—in the worst case—falling. Occurring events are forwarded to the nursing staff immediately by using a modular, self-organizing and dependable wireless infrastructure. Both, the hardware and software of the entire INBED system as well as the particular design process are discussed in detail. Moreover, a trail test of the system is presented. Conclusions: The INBED system can help to relieve the nursing staff significantly while the personal freedom of movement and the privacy of patients is increased compared to similar systems. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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19 pages, 2972 KiB

Open AccessArticle

Modular Pressure and Flow Rate-Balanced Microfluidic Serial Dilution Networks for Miniaturised Point-of-Care Diagnostic Platforms

by Nikolaos Vasilakis, Konstantinos I. Papadimitriou, Hywel Morgan and Themistoklis Prodromakis

Sensors 2019, 19(4), 911; https://doi.org/10.3390/s19040911 - 21 Feb 2019

Cited by 5 | Viewed by 6466

Abstract

Fast, efficient and more importantly accurate serial dilution is a necessary requirement for most biochemical microfluidic-based quantitative diagnostic applications. Over the last two decades, a multitude of microfluidic devices has been proposed, each one demonstrating either a different type of dilution technique or complex system architecture based on various flow source and valving combinations. In this work, a novel serial dilution network architecture is demonstrated, implemented on two entirely different substrates for validation and performance characterisation. The single layer, stepwise serial diluter comprises an optimised microfluidic network, where identical dilution ratios per stage are ensured, either by applying equal pressure or equal flow rates at both inlets. The advantages of this serial diluter are twofold: Firstly, it is structured as a modular unit cell, simplifying the required fluid driving mechanism to a single source for both sample and buffer solution. Thus, this unit cell can be used as a fundamental microfluidic building block, forming multistage serial dilution cascades, once combined appropriately with itself or other similar unit cells. Secondly, the serial diluter can tolerate the inevitable flow source fluctuations, ensuring constant dilution ratios without the need to employ damping mechanisms, making it ideal for Point of Care (PoC) platforms. Proof-of-concept experiments with glucose have demonstrated good agreement between simulations and measurements, highlighting the validity of our serial diluter. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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9 pages, 2176 KiB

Open AccessArticle

An Optimized Colorimetric Readout Method for Lateral Flow Immunoassays

by Jongwon Park

Sensors 2018, 18(12), 4084; https://doi.org/10.3390/s18124084 - 22 Nov 2018

Cited by 19 | Viewed by 6032

Abstract

Despite its broad penetration of various markets, the quantitative lateral flow immunoassay (LFIA) suffers from sensitivity issues in some cases. To solve this problem, an optimized colorimetric readout method for LFIA quantification is proposed in this study. An assay reader device utilizing a color camera and an analysis method using a Bayer filtered image were developed. Spectrometric measurements of the assay test line were performed to determine the color channel that contains the test line information and effectively minimizes noise. The change in the intensity ratio with increasing concentration of the target substance in the sample was largest in the green channel. The linear range of the output curve ranged from 0 to 10 ng/mL, and the detection limit was 2 ng/mL. The suggested instrumentation and analysis methods are expected to effectively resolve the low-sensitivity problems of the former LFIA systems and to offer other prospective functionalities for LFIA quantification. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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10 pages, 1003 KiB

Open AccessArticle

Validity and Repeatability of Single-Sensor Loadsol Insoles during Landing

by Alexander T. Peebles, Lindsay A. Maguire, Kristen E. Renner and Robin M. Queen

Sensors 2018, 18(12), 4082; https://doi.org/10.3390/s18124082 - 22 Nov 2018

Cited by 51 | Viewed by 5427

Abstract

Clinically feasible methods for quantifying landing kinetics could help identify patients at risk for secondary anterior cruciate ligament injuries. The purpose of this study was to evaluate the validity and between-day repeatability of the loadsol insole during a single-hop and bilateral stop-jump. Thirty healthy recreational athletes completed seven single-hops and seven stop-jumps while simultaneous loadsol (100 Hz) and force plate (1920 Hz) measurements were recorded. Peak impact force, loading rate, and impulse were computed for the dominant limb, and limb symmetry was calculated between limbs for each measure. All outcomes were compared between the loadsol and force plate using intraclass correlation coefficients (ICC) and Bland–Altman plots. Fifteen participants completed a second day of testing to assess between-day repeatability of the loadsol. Finally, an additional 14 participants completed the first day of testing only to assess the validity of the newest generation loadsol, which sampled at 200 Hz. At 100 Hz, validity ICC results were moderate to excellent (0.686–0.982), and repeatability ICC results were moderate to excellent (0.616–0.928). The 200 Hz loadsol demonstrated improved validity ICC (0.765–0.987). Bland–Altman plots revealed that the loadsol underestimated load measures. However, this bias was not observed for symmetry outcomes. The loadsol device is a valid and repeatable tool for evaluating kinetics during landing. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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14 pages, 2445 KiB

Open AccessArticle

A Novel Microfluidic Point-of-Care Biosensor System on Printed Circuit Board for Cytokine Detection

by Daniel Evans, Konstantinos I. Papadimitriou, Nikolaos Vasilakis, Panagiotis Pantelidis, Peter Kelleher, Hywel Morgan and Themistoklis Prodromakis

Sensors 2018, 18(11), 4011; https://doi.org/10.3390/s18114011 - 17 Nov 2018

Cited by 37 | Viewed by 6804

Abstract

Point of Care (PoC) diagnostics have been the subject of considerable research over the last few decades driven by the pressure to detect diseases quickly and effectively and reduce healthcare costs. Herein, we demonstrate a novel, fully integrated, microfluidic amperometric enzyme-linked immunosorbent assay (ELISA) prototype using a commercial interferon gamma release assay (IGRA) as a model antibody binding system. Microfluidic assay chemistry was engineered to take place on Au-plated electrodes within an assay cell on a printed circuit board (PCB)-based biosensor system. The assay cell is linked to an electrochemical reporter cell comprising microfluidic architecture, Au working and counter electrodes and a Ag/AgCl reference electrode, all manufactured exclusively via standard commercial PCB fabrication processes. Assay chemistry has been optimised for microfluidic diffusion kinetics to function under continual flow. We characterised the electrode integrity of the developed platforms with reference to biological sampling and buffer composition and subsequently we demonstrated concentration-dependent measurements of H₂O₂ depletion as resolved by existing FDA-validated ELISA kits. Finally, we validated the assay technology in both buffer and serum and demonstrate limits of detection comparable to high-end commercial systems with the addition of full microfluidic assay architecture capable of returning diagnostic analyses in approximately eight minutes. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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14 pages, 5384 KiB

Open AccessArticle

Three-Dimensional High-Resolution Digital Inline Hologram Reconstruction with a Volumetric Deconvolution Method

by Junseong Eom and Sangjun Moon

Sensors 2018, 18(9), 2918; https://doi.org/10.3390/s18092918 - 3 Sep 2018

Cited by 12 | Viewed by 4684

Abstract

The digital in-line holographic microscope (DIHM) was developed for a 2D imaging technology and has recently been adapted to 3D imaging methods, providing new approaches to obtaining volumetric images with both a high resolution and wide field-of-view (FOV), which allows the physical limitations to be overcome. However, during the sectioning process of 3D image generation, the out-of-focus image of the object becomes a significant impediment to obtaining evident 3D features in the 2D sectioning plane of a thick biological sample. Based on phase retrieved high-resolution holographic imaging and a 3D deconvolution technique, we demonstrate that a high-resolution 3D volumetric image, which significantly reduces wave-front reconstruction and out-of-focus artifacts, can be achieved. The results show a 3D volumetric image that is more finely focused compared to a conventional 3D stacked image from 2D reconstructed images in relation to micron-size polystyrene beads, a whole blood smear, and a kidney tissue sample. We believe that this technology can be applicable for medical-grade images of smeared whole blood or an optically cleared tissue sample for mobile phytological microscopy and laser sectioning microscopy. Full article

(This article belongs to the Special Issue Portable Biosensing Systems for Point-of-Care Diagnostic Applications)

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