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This study presents a portable, low-cost, point-of-care (POC) system for the simultaneous detection of blood glucose and hematocrit. The system consists of a disposable origami microfluidic paper-based analytical device (μPAD) for plasma separation, filtration, and reaction functions and a 3D-printed cassette for hematocrit and blood glucose detection using a smartphone. The origami μPAD is patterned using a cost-effective label printing technique instead of the conventional wax printing method. The 3D-printed cassette incorporates an array of LED lights, which mitigates the effects of intensity variations in the ambient light and hence improves the accuracy of the blood glucose and hematocrit concentration measurements. The hematocrit concentration is determined quantitatively by measuring the distance of plasma wicking along the upper layer of the origami μPAD, which is pretreated with sodium chloride and Tween 20 to induce dehydration and aggregation of the red blood cells. The filtered plasma also penetrates to the lower layer of the origami μPAD, where it reacts with embedded colorimetric assay reagents to produce a yellowish-brown complex. A color image of the reaction complex is captured using a smartphone inserted into the 3D-printed cassette. The image is analyzed using self-written RGB software to quantify the blood glucose concentration. The calibration results indicate that the proposed detection platform provides an accurate assessment of the blood glucose level over the range of 45–630 mg/dL (R2 = 0.9958). The practical feasibility of the proposed platform is demonstrated by measuring the blood glucose and hematocrit concentrations in 13 human whole blood samples. Taking the measurements obtained from commercial glucose and hematocrit meters as a benchmark, the proposed system has a differential of no more than 6.4% for blood glucose detection and 9.1% for hematocrit detection. Overall, the results confirm that the proposed μPAD is a promising solution for cost-effective and reliable POC health monitoring. [ABSTRACT FROM AUTHOR]

Quick and effective point-of-care (POC) devices have the chance to revolutionize healthcare in developed and developing countries since they can operate anywhere the patient is, with the possibility of obtaining and sending the results to the doctor without delay. In recent years, significant efforts have focused on developing new POC systems that can screen for biomarkers continuously and non-invasively in body fluids to prevent, diagnose, and manage diseases. However, one of the critical challenges left to address is how to power them effectively and sufficiently. In developing countries and rural and remote areas, where there are usually no well-established electricity grids or nearby medical facilities, and using batteries is unreliable or not cost-effective, alternative power sources are the most challenging issue for stand-alone and self-sustained POC devices. Here, we provide an overview of the techniques for used self-powering POC devices, where the sample is used to detect and simultaneously generate energy to power the system. Likewise, this paper introduced the state-of-the-art with a review of different research projects, patents, and commercial products for self-powered POCs from the mid-2010s until present day. [ABSTRACT FROM AUTHOR]

For the progress of point-of-care medicine, where individual health status can be easily and quickly monitored using a handheld sensor, saliva serves as one of the best-suited body fluids thanks to its availability and abundance of physiological indicators. Salivary biomarkers, combined with rapid and highly sensitive detection tools, may pave the way to new real-time health monitoring and personalized preventative therapy branches using saliva as a target matrix. Saliva is increasing in importance in liquid biopsy, a non-invasive approach that helps physicians diagnose and characterize specific diseases in patients. Here, we propose a proof-of-concept study combining the unique specificity in biomolecular recognition provided by surface-enhanced Raman spectroscopy (SERS) in combination with molecular dynamics (MD) simulations, which give leave to explore the biomolecular absorption mechanism on nanoparticle surfaces, in order to verify the traceability of two validated salivary indicators, i.e., interleukin-8 (IL-8) and lysozyme (LYZ), implicated in oropharyngeal squamous cell carcinoma (OSCC) and oral infection. This strategy simultaneously assures the detection and interpretation of protein biomarkers in saliva, ultimately opening a new route for the evolution of fast and accurate point-of-care SERS-based sensors of interest in precision medicine diagnostics. [ABSTRACT FROM AUTHOR]

Fluorescence-based detection techniques are part of an ever-expanding field and are widely used in biomedical and environmental research as a biosensing tool. These techniques have high sensitivity, selectivity, and a short response time, making them a valuable tool for developing bio-chemical assays. The endpoint of these assays is defined by changes in fluorescence signal, in terms of its intensity, lifetime, and/or shift in spectrum, which is monitored using readout devices such as microscopes, fluorometers, and cytometers. However, these devices are often bulky, expensive, and require supervision to operate, which makes them inaccessible in resource-limited settings. To address these issues, significant effort has been directed towards integrating fluorescence-based assays into miniature platforms based on papers, hydrogels, and microfluidic devices, and to couple these assays with portable readout devices like smartphones and wearable optical sensors, thereby enabling point-of-care detection of bio-chemical analytes. This review highlights some of the recently developed portable fluorescence-based assays by discussing the design of fluorescent sensor molecules, their sensing strategy, and the fabrication of point-of-care devices. [ABSTRACT FROM AUTHOR]

With rising healthcare costs and the rapid increase in remote physiologic monitoring and care delivery, there is an increasing need for economical, accurate, and non-invasive continuous measures of blood analytes. Based on radio frequency identification (RFID), a novel electromagnetic technology (the Bio-RFID sensor) was developed to non-invasively penetrate inanimate surfaces, capture data from individual radio frequencies, and convert those data into physiologically meaningful information and insights. Here, we describe groundbreaking proof-of-principle studies using Bio-RFID to accurately measure various concentrations of analytes in deionized water. In particular, we tested the hypothesis that the Bio-RFID sensor is able to precisely and non-invasively measure and identify a variety of analytes in vitro. For this assessment, varying solutions of (1) water in isopropyl alcohol; (2) salt in water, and (3) commercial bleach in water were tested, using a randomized double-blind trial design, as proxies for biochemical solutions in general. The Bio-RFID technology was able to detect concentrations of 2000 parts per million (ppm), with evidence suggesting the ability to detect considerably smaller concentration differences. [ABSTRACT FROM AUTHOR]

Since its first report in 2006, magnetic particle spectroscopy (MPS)-based biosensors have flourished over the past decade. Currently, MPS are used for a wide range of applications, such as disease diagnosis, foodborne pathogen detection, etc. In this work, different MPS platforms, such as dual-frequency and mono-frequency driving field designs, were reviewed. MPS combined with multi-functional magnetic nanoparticles (MNPs) have been extensively reported as a versatile platform for the detection of a long list of biomarkers. The surface-functionalized MNPs serve as nanoprobes that specifically bind and label target analytes from liquid samples. Herein, an analysis of the theories and mechanisms that underlie different MPS platforms, which enable the implementation of bioassays based on either volume or surface, was carried out. Furthermore, this review draws attention to some significant MPS platform applications in the biomedical and biological fields. In recent years, different kinds of MPS point-of-care (POC) devices have been reported independently by several groups in the world. Due to the high detection sensitivity, simple assay procedures and low cost per run, the MPS POC devices are expected to become more widespread in the future. In addition, the growth of telemedicine and remote monitoring has created a greater demand for POC devices, as patients are able to receive health assessments and obtain results from the comfort of their own homes. At the end of this review, we comment on the opportunities and challenges for POC devices as well as MPS devices regarding the intensely growing demand for rapid, affordable, high-sensitivity and user-friendly devices. [ABSTRACT FROM AUTHOR]

Hematocrit (HCT) is a crucial parameter for both adult and pediatric patients, indicating potentially severe pathological conditions. Most common methods for HCT assessment are microhematocrit and automated analyzers; however, developing countries present specific needs often not addressed by these technologies. Paper-based devices can be suitable for those environments being inexpensive, rapid, easy to use, and portable. The aim of this study is to describe and validate against a reference method, a novel HCT estimation method based on penetration velocity in lateral flow test strips complying with the requirements in low- or middle-income country (LMIC) scenarios. To calibrate and test the proposed method, 145 blood samples of 105 healthy neonates with gestational age greater than 37 weeks were collected (29 calibration set, 116 test set) in the range of HCT values (31.6–72.5%). The time difference (Δt) from the whole blood sample loading into the test strip instant till the nitrocellulose membrane saturation instant was measured by a reflectance meter. A nonlinear relation was observed between HCT and Δt and was estimated by a third-degree polynomial equation (R2 = 0.91) valid in 30% to 70% HCT interval. The proposed model was subsequently used to estimate HCT values on the test set showing a good agreement between the estimated HCT and the HCT measured by the reference method (r = 0.87, p < 0.001), with a low mean difference of 0.53 ± 5.04% and a slight trend of overestimation for higher hematocrit values. The mean absolute error was 4.29%, while the maximum absolute error was 10.69%. Although the proposed method did not present a sufficient accuracy to be used for diagnostic purposes, it could be suitable as a fast, low-cost, easy-to-use screening tool especially in LMIC scenarios. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for accurate early diagnosis and monitoring. A label-free rapid electrochemical point-of-care (POC) biosensor for SARS-CoV-2 detection in human saliva is reported here to help address the shortcomings of traditional nucleic acid amplification methods and give a quantitative assessment of the viral load to track infection status anywhere, using disposable electrochemical sensor chips. A new chemical construct of gold nanoparticles (GNp) and thionine (Th) are immobilized on carboxylic acid functionalized carbon nanotubes (SWCNT-COOH) for high-performance biosensing. The sensor uses saliva with a one-step pretreatment and simple testing procedure as an analytical medium due to the user-friendly and non-invasive nature of its procurement from patients. The sensor has a response time of 5 min with a limit of detection (LOD) reaching 200 and 500 pM for the freely suspended spike (S) protein in phosphate buffer saline (PBS) and human saliva, respectively. The sensor's performance was also proven for detecting a COVID-19 pseudovirus in an electrolyte solution with a LOD of 106 copies/mL. The results demonstrate that the optimized POC sensor developed in this work is a promising device for the label-free electrochemical biosensing detection of SARS-CoV-2 and different species of viruses. [ABSTRACT FROM AUTHOR]

World population and life expectancy have increased steadily in recent years, raising issues regarding access to medical treatments and related expenses. Through last-generation medical sensors, NFC (Near Field Communication) and radio frequency identification (RFID) technologies can enable healthcare internet of things (H-IoT) systems to improve the quality of care while reducing costs. Moreover, the adoption of point-of-care (PoC) testing, performed whenever care is needed to return prompt feedback to the patient, can generate great synergy with NFC/RFID H-IoT systems. However, medical data are extremely sensitive and require careful management and storage to protect patients from malicious actors, so secure system architectures must be conceived for real scenarios. Existing studies do not analyze the security of raw data from the radiofrequency link to cloud-based sharing. Therefore, two novel cloud-based system architectures for data collected from NFC/RFID medical sensors are proposed in this paper. Privacy during data collection is ensured using a set of classical countermeasures selected based on the scientific literature. Then, data can be shared with the medical team using one of two architectures: in the first one, the medical system manages all data accesses, whereas in the second one, the patient defines the access policies. Comprehensive analysis of the H-IoT system can be useful for fostering research on the security of wearable wireless sensors. Moreover, the proposed architectures can be implemented for deploying and testing NFC/RFID-based healthcare applications, such as, for instance, domestic PoCs. [ABSTRACT FROM AUTHOR]

This work studies the feasibility of using a battery-less Near-Field Communication (NFC) potentiostat for the next generation of electrochemical point-of-care sensors. A design based on an NFC microchip, a microcontroller, and a custom potentiostat based on an operational amplifier is presented. A proof-of-concept prototype has been designed and used to quantify glucose concentration using commercial glucose test strips from chronoamperometry measurements. The device is harvested and the sensor is read using a mobile phone. The prototype uses an antenna loop covered with ferrite sheets to ensure stable operation of the electronics when the mobile phone is used as reader. The use of ferrite reduces the detuning caused by the proximity of the metal parts of the mobile phone. A comparison with a commercial glucometer device is provided. Results obtained using a commercial glucometer and those provided by the proposed potentiostat show an excellent agreement. [ABSTRACT FROM AUTHOR]

Weight loss through dietary and exercise intervention is commonly prescribed but is not effective for all individuals. Recent studies have demonstrated that circulating microRNA (miR) biomarkers could potentially be used to identify individuals who will likely lose weight through diet and exercise and attain a healthy body weight. However, accurate detection of miRs in clinical samples is difficult, error-prone, and expensive. To address this issue, we recently developed iLluminate—a low-cost and highly sensitive miR sensor suitable for point-of-care testing. To investigate if miR testing and iLluminate can be used in real-world obesity applications, we developed a pilot diet and exercise intervention and utilized iLluminate to evaluate miR biomarkers. We evaluated the expression of miRs-140, -935, -let-7b, and -99a, which are biomarkers for fat loss, energy metabolism, and adipogenic differentiation. Responders lost more total mass, tissue mass, and fat mass than non-responders. miRs-140, -935, -let-7b, and -99a, collectively accounted for 6.9% and 8.8% of the explained variability in fat and lean mass, respectively. At the level of the individual coefficients, miRs-140 and -935 were significantly associated with fat loss. Collectively, miRs-140 and -935 provide an additional degree of predictive capability in body mass and fat mass alternations. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MS) is a cluster of conditions that increases the probability of heart disease, stroke, and diabetes, and is very common worldwide. While the exact cause of MS has yet to be understood, there is evidence indicating the relationship between MS and the dysregulation of the immune system. The resultant biomarkers that are expressed in the process are gaining relevance in the early detection of related MS. However, sensing only a single analyte has its limitations because one analyte can be involved with various conditions. Thus, for MS, which generally results from the co-existence of multiple complications, a multi-analyte sensing platform is necessary for precise diagnosis. In this review, we summarize various types of biomarkers related to MS and the non-invasively accessible biofluids that are available for sensing. Then two types of widely used sensing platform, the electrochemical and optical, are discussed in terms of multimodal biosensing, figure-of-merit (FOM), sensitivity, and specificity for early diagnosis of MS. This provides a thorough insight into the current status of the available platforms and how the electrochemical and optical modalities can complement each other for a more reliable sensing platform for MS. [ABSTRACT FROM AUTHOR]

Detecting biomarkers is an efficient method to diagnose and monitor patients’ stages. For more accurate diagnoses, continuously detecting and monitoring multiple biomarkers are needed. To achieve point-of-care testing (POCT) of multiple biomarkers, a smartphone biosensor system with the multi-testing-unit (SBSM) based on localized surface plasmon resonance (LSPR) integrated multi-channel microfluidics was presented. The SBSM could simultaneously record nine sensor units to achieve the detection of multiple biomarkers. Additional 72 sensor units were fabricated for further verification. Well-designed modularized attachments consist of a light source, lenses, a grating, a case, and a smartphone shell. The attachments can be well assembled and attached to a smartphone. The sensitivity of the SBSM was 161.0 nm/RIU, and the limit of detection (LoD) reached 4.2 U/mL for CA125 and 0.87 U/mL for CA15-3 through several clinical serum specimens testing on the SBSM. The testing results indicated that the SBSM was a useful tool for detecting multi-biomarkers. Comparing with the enzyme-linked immunosorbent assays (ELISA) results, the results from the SBSM were correlated and reliable. Meanwhile, the SBSM was convenient to operate without much professional skill. Therefore, the SBSM could become useful equipment for point-of-care testing due to its small size, multi-testing unit, usability, and customizable design. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) and cancer are two leading causes of death worldwide. CVD and cancer share risk factors such as obesity and diabetes mellitus and have common diagnostic biomarkers such as interleukin-6 and C-reactive protein. Thus, timely and accurate diagnosis of these two correlated diseases is of high interest to both the research and healthcare communities. Most conventional methods for CVD and cancer biomarker detection such as microwell plate-based immunoassay and polymerase chain reaction often suffer from high costs, low test speeds, and complicated procedures. Recently, lab-on-a-chip (LoC)-based platforms have been increasingly developed for CVD and cancer biomarker sensing and analysis using various molecular and cell-based diagnostic biomarkers. These new platforms not only enable better sample preparation, chemical manipulation and reaction, high-throughput and portability, but also provide attractive features such as label-free detection and improved sensitivity due to the integration of various novel detection techniques. These features effectively improve the diagnostic test speed and simplify the detection procedure. In addition, microfluidic cell assays and organ-on-chip models offer new potential approaches for CVD and cancer diagnosis. Here we provide a mini-review focusing on recent development of LoC-based methods for CVD and cancer diagnostic biomarker measurements, and our perspectives of the challenges, opportunities and future directions. [ABSTRACT FROM AUTHOR]

Currently, Cystic Fibrosis (CF) patients lack the ability to track their lung health at home, relying instead on doctor checkups leading to delayed treatment and lung damage. By leveraging the ubiquity of the smartphone to lower costs and increase portability, a smartphone-based peripheral pH measurement device was designed to attach directly to the headphone port to harvest power and communicate with a smartphone application. This platform was tested using prepared pH buffers and sputum samples from CF patients. The system matches within ~0.03 pH of a benchtop pH meter while fully powering itself and communicating with a Samsung Galaxy S3 smartphone paired with either a glass or Iridium Oxide (IrOx) electrode. The IrOx electrodes were found to have 25% higher sensitivity than the glass probes at the expense of larger drift and matrix sensitivity that can be addressed with proper calibration. The smartphone-based platform has been demonstrated as a portable replacement for laboratory pH meters, and supports both highly robust glass probes and the sensitive and miniature IrOx electrodes with calibration. This tool can enable more frequent pH sputum tracking for CF patients to help detect the onset of pulmonary exacerbation to provide timely and appropriate treatment before serious damage occurs. [ABSTRACT FROM AUTHOR]

Dielectrophoresis (DEP) is a label-free, accurate, fast, low-cost diagnostic technique that uses the principles of polarization and the motion of bioparticles in applied electric fields. This technique has been proven to be beneficial in various fields, including environmental research, polymer research, biosensors, microfluidics, medicine and diagnostics. Biomedical science research is one of the major research areas that could potentially benefit from DEP technology for diverse applications. Nevertheless, many medical science research investigations have yet to benefit from the possibilities offered by DEP. This paper critically reviews the fundamentals, recent progress, current challenges, future directions and potential applications of research investigations in the medical sciences utilizing DEP technique. This review will also act as a guide and reference for medical researchers and scientists to explore and utilize the DEP technique in their research fields. [ABSTRACT FROM AUTHOR]

Protein microarrays represent a powerful technology with the potential to serve as tools for the detection of a broad range of analytes in numerous applications such as diagnostics, drug development, food safety, and environmental monitoring. Key features of analytical protein microarrays include high throughput and relatively low costs due to minimal reagent consumption, multiplexing, fast kinetics and hence measurements, and the possibility of functional integration. So far, especially fundamental studies in molecular and cell biology have been conducted using protein microarrays, while the potential for clinical, notably point-of-care applications is not yet fully utilized. The question arises what features have to be implemented and what improvements have to be made in order to fully exploit the technology. In the past we have identified various obstacles that have to be overcome in order to promote protein microarray technology in the diagnostic field. Issues that need significant improvement to make the technology more attractive for the diagnostic market are for instance: too low sensitivity and deficiency in reproducibility, inadequate analysis time, lack of high-quality antibodies and validated reagents, lack of automation and portable instruments, and cost of instruments necessary for chip production and read-out. The scope of the paper at hand is to review approaches to solve these problems. [ABSTRACT FROM AUTHOR]

We present a 72 × 60, angle-sensitive single photon avalanche diode (A-SPAD) array for lens-less 3D fluorescence lifetime imaging. An A-SPAD pixel consists of (1) a SPAD to provide precise photon arrival time where a time-resolved operation is utilized to avoid stimulus-induced saturation, and (2) integrated diffraction gratings on top of the SPAD to extract incident angles of the incoming light. The combination enables mapping of fluorescent sources with different lifetimes in 3D space down to micrometer scale. Futhermore, the chip presented herein integrates pixel-level counters to reduce output data-rate and to enable a precise timing control. The array is implemented in standard 180 nm complementary metal-oxide-semiconductor (CMOS) technology and characterized without any post-processing. [ABSTRACT FROM AUTHOR]

Despite the copious amount of research on the design and operation of micromixers, there are few works regarding manufacture technology aimed at implementation beyond academic environments. This work evaluates the viability of xurography as a rapid fabrication tool for the development of ultra-low cost microfluidic technology for extreme Point-of-Care (POC) micromixing devices. By eschewing photolithographic processes and the bulkiness of pumping and enclosure systems for rapid fabrication and passively driven operation, xurography is introduced as a manufacturing alternative for asymmetric split and recombine (ASAR) micromixers. A T-micromixer design was used as a reference to assess the effects of different cutting conditions and materials on the geometric features of the resulting microdevices. Inspection by stereographic and confocal microscopy showed that it is possible to manufacture devices with less than 8% absolute dimensional error. Implementation of the manufacturing methodology in modified circular shape- based SAR microdevices (balanced and unbalanced configurations) showed that, despite the precision limitations of the xurographic process, it is possible to implement this methodology to produce functional micromixing devices. Mixing efficiency was evaluated numerically and experimentally at the outlet of the microdevices with performances up to 40%. Overall, the assessment encourages further research of xurography for the development of POC micromixers. [ABSTRACT FROM AUTHOR]

We present a small, compact and portable device for point-of-care instantaneous early detection of anemia. The method used is based on direct hematocrit measurement from whole blood samples by means of impedance analysis. This device consists of a custom electronic instrumentation and a plug-and-play disposable sensor. The designed electronics rely on straightforward standards for low power consumption, resulting in a robust and low consumption device making it completely mobile with a long battery life. Another approach could be powering the system based on other solutions like indoor solar cells, or applying energy-harvesting solutions in order to remove the batteries. The sensing system is based on a disposable low-cost label-free three gold electrode commercial sensor for 50 µL blood samples. The device capability for anemia detection has been validated through 24 blood samples, obtained from four hospitalized patients at Hospital Clínic. As a result, the response, effectiveness and robustness of the portable point-of-care device to detect anemia has been proved with an accuracy error of 2.83% and a mean coefficient of variation of 2.57% without any particular case above 5%. [ABSTRACT FROM AUTHOR]

This review investigates optical sensor platforms for protein multiplexing, the ability to analyze multiple analytes simultaneously. Multiplexing is becoming increasingly important for clinical needs because disease and therapeutic response often involve the interplay between a variety of complex biological networks encompassing multiple, rather than single, proteins. Multiplexing is generally achieved through one of two routes, either through spatial separation on a surface (different wells or spots) or with the use of unique identifiers/labels (such as spectral separation-different colored dyes, or unique beads-size or color). The strengths and weaknesses of conventional platforms such as immunoassays and new platforms involving protein arrays and lab-on-a-chip technology, including commercially-available devices, are discussed. Three major public health concerns are identified whereby detecting medically-relevant markers using Point-of-Care (POC) multiplex assays could potentially allow for a more efficient diagnosis and treatment of diseases. [ABSTRACT FROM AUTHOR]

Instrumental limitations such as bulkiness and high cost prevent the fluorescence technique from becoming ubiquitous for point-of-care deoxyribonucleic acid (DNA) detection and other in-field molecular diagnostics applications. The complimentary metal-oxide-semiconductor (CMOS) technology, as benefited from process scaling, provides several advanced capabilities such as high integration density, high-resolution signal processing, and low power consumption, enabling sensitive, integrated, and low-cost fluorescence analytical platforms. In this paper, CMOS time-resolved, contact, and multispectral imaging are reviewed. Recently reported CMOS fluorescence analysis microsystem prototypes are surveyed to highlight the present state of the art. [ABSTRACT FROM AUTHOR]

A multiplexed microfluidic biosensor made of poly(methylmethacrylate) (PMMA) was integrated into an array of organic blend heterojunction photodiodes (OPDs) for chemiluminescent detection of pathogens. Waterborne Escherichia coli O157:H7, Campylobacter jejuni and adenovirus were targeted in the PMMA chip, and detection of captured pathogens was conducted by poly(2,7-carbazole)/fullerene OPDs which showed a responsivity over 0.20 A/W at 425 nm. The limits of chemiluminescent detection were 5 x 105 cells/mL for E. coli, 1 x 105 cells/mL for C. jejuni, and 1 x 10-8 mg/mL for adenovirus. Parallel analysis for all three analytes in less than 35 min was demonstrated. Further recovery tests illustrated the potential of the integrated biosensor for detecting bacteria in real water samples. [ABSTRACT FROM AUTHOR]

This study was conducted to develop a simple, rapid, and accurate lateral flow immunoassay (LFIA) detection method for point-of-care diagnosis. The one-dot LFIA for aflatoxin B1 (AFB1) was based on the modified competitive binding format using competition between AFB1 and colloidal gold-AFB1-BSA conjugate for antibody binding sites in the test zone. A Smartphone-based reading system consisting of a Samsung Galaxy S2 Smartphone, a LFIA reader, and a Smartphone application for the image acquisition and data analysis. The detection limit of one-dot LFIA for AFB1 is 5 µg/kg. This method provided semi-quantitative analysis of AFB1 samples in the range of 5 to 1,000 µg/kg. Using combination of the one-dot LFIA and the Smartphone-based reading system, it is possible to conduct a more fast and accurate point-of-care diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Advances in lab-on-a-chip systems have strong potential for multiplexed detection of a wide range of analytes with reduced sample and reagent volume; lower costs and shorter analysis times. The completion of high-fidelity multiplexed and multiclass assays remains a challenge for the medical microdevice field; as it struggles to achieve and expand upon at the point-of-care the quality of results that are achieved now routinely in remote laboratory settings. This review article serves to explore for the first time the key intersection of multiplexed bead-based detection systems with integrated microfluidic structures alongside porous capture elements together with biomarker validation studies. These strategically important elements are evaluated here in the context of platform generation as suitable for near-patient testing. Essential issues related to the scalability of these modular sensor ensembles are explored as are attempts to move such multiplexed and multiclass platforms into large-scale clinical trials. Recent efforts in these bead sensors have shown advantages over planar microarrays in terms of their capacity to generate multiplexed test results with shorter analysis times. Through high surface-to-volume ratios and encoding capabilities; porous bead-based ensembles; when combined with microfluidic elements; allow for high-throughput testing for enzymatic assays; general chemistries; protein; antibody and oligonucleotide applications. [ABSTRACT FROM AUTHOR]

Changes in mass loading on the surface of acoustic biosensors result in output frequency shifts which provide precise measurements of analytes. Therefore, to detect a particular biomarker, the sensor delay path must be judiciously designed to maximize sensitivity and specificity. B-cell lymphoma 2 protein (Bcl-2) found in urine is under investigation as a biomarker for non-invasive early detection of ovarian cancer. In this study, surface chemistry and biofunctionalization approaches were evaluated for their effectiveness in presenting antibodies for Bcl-2 capture while minimizing non-specific protein adsorption. The optimal combination of sequentially adsorbing protein A/G, anti-Bcl-2 IgG and Pluronic F127 onto a hydrophobic surface provided the greatest signal-to-noise ratio and enabled the reliable detection of Bcl-2 concentrations below that previously identified for early stage ovarian cancer as characterized by a modified ELISA method. Finally, the optimal surface modification was applied to a prototype acoustic device and the frequency shift for a range of Bcl-2 concentration was quantified to demonstrate the effectiveness in surface acoustic wave (SAW)-based detection applications. The surface functionalization approaches demonstrated here to specifically and sensitively detect Bcl-2 in a working ultrasonic MEMS biosensor prototype can easily be modified to detect additional biomarkers and enhance other acoustic biosensors. [ABSTRACT FROM AUTHOR]

In this study, we propose a low-area multi-channel controlled dielectric breakdown (CDB) system that simultaneously produces several nanopore sensors. Conventionally, solid-state nanopores are prepared by etching or drilling openings in a silicon nitride (SiNx) substrate, which is expensive and requires a long processing time. To address these challenges, a CDB technique was introduced and used to fabricate nanopore channels in SiNx membranes. However, the nanopore sensors produced by the CDB result in a severe pore-to-pore diameter variation as a result of different fabrication conditions and processing times. Accordingly, it is indispensable to simultaneously fabricate nanopore sensors in the same environment to reduce the deleterious effects of pore-to-pore variation. In this study, we propose a four-channel CDB system that comprises an amplifier that boosts the command voltage, a 1-to-4 multiplexer, a level shifter, a low-noise transimpedance amplifier and a data acquisition device. To prove our design concept, we used the CDB system to fabricate four nanopore sensors with diameters of <10 nm, and its in vitro performance was verified using λ-DNA samples. [ABSTRACT FROM AUTHOR]

In this review, a selection of works on the sensing of biomarkers related to diabetes mellitus (DM) and diabetic retinopathy (DR) are presented, with the scope of helping and encouraging researchers to design sensor-array machine-learning (ML)-supported devices for robust, fast, and cost-effective early detection of these devastating diseases. First, we highlight the social relevance of developing systematic screening programs for such diseases and how sensor-arrays and ML approaches could ease their early diagnosis. Then, we present diverse works related to the colorimetric and electrochemical sensing of biomarkers related to DM and DR with non-invasive sampling (e.g., urine, saliva, breath, tears, and sweat samples), with a special mention to some already-existing sensor arrays and ML approaches. We finally highlight the great potential of the latter approaches for the fast and reliable early diagnosis of DM and DR. [ABSTRACT FROM AUTHOR]

Recently, the amount of attention paid towards convolutional neural networks (CNN) in medical image analysis has rapidly increased since they can analyze and classify images faster and more accurately than human abilities. As a result, CNNs are becoming more popular and play a role as a supplementary assistant for healthcare professionals. Using the CNN on portable medical devices can enable a handy and accurate disease diagnosis. Unfortunately, however, the CNNs require high-performance computing resources as they involve a significant amount of computation to process big data. Thus, they are limited to being used on portable medical devices with limited computing resources. This paper discusses the network quantization techniques that reduce the size of CNN models and enable fast CNN inference with an energy-efficient CNN accelerator integrated into recent mobile processors. With extensive experiments, we show that the quantization technique reduces inference time by 97% on the mobile system integrating a CNN acceleration engine. [ABSTRACT FROM AUTHOR]

This paper proposes a cloud-based software architecture for fully automated point-of-care molecular diagnostic devices. The target system operates a cartridge consisting of an extraction body for DNA extraction and a PCR chip for amplification and fluorescence detection. To facilitate control and monitoring via the cloud, a socket server was employed for fundamental molecular diagnostic functions such as DNA extraction, amplification, and fluorescence detection. The user interface for experimental control and monitoring was constructed with the RESTful application programming interface, allowing access from the terminal device, edge, and cloud. Furthermore, it can also be accessed through any web-based user interface on smart computing devices such as smart phones or tablets. An emulator with the proposed software architecture was fabricated to validate successful operation. [ABSTRACT FROM AUTHOR]

Monitoring the immune system's status has emerged as an urgent demand in critical health conditions. The circulating cytokine levels in the blood reflect a thorough insight into the immune system status. Indeed, measuring one cytokine may deliver more information equivalent to detecting multiple diseases at a time. However, if the reported cytokine levels are interpreted with considering lifestyle and any comorbid health conditions for the individual, this will promote a more precise assessment of the immune status. Therefore, this study addresses the most recent advanced assays that deliver rapid, accurate measuring of the cytokine levels in human blood, focusing on add-on potentials for point-of-care (PoC) or personal at-home usage, and investigates existing health questionnaires as supportive assessment tools that collect all necessary information for the concrete analysis of the measured cytokine levels. We introduced a ten-dimensional featuring of cytokine measurement assays. We found 15 rapid cytokine assays with assay time less than 1 h; some could operate on unprocessed blood samples, while others are mature commercial products available in the market. In addition, we retrieved several health questionnaires that addressed various health conditions such as chronic diseases and psychological issues. Then, we present a machine learning-based solution to determine what makes the immune system fit. To this end, we discuss how to employ topic modeling for deriving the definition of immune fitness automatically from literature. Finally, we propose a prototype model to assess the fitness of the immune system through leveraging the derived definition of the immune fitness, the cytokine measurements delivered by a rapid PoC immunoassay, and the complementary information collected by the health questionnaire about other health factors. In conclusion, we discovered various advanced rapid cytokine detection technologies that are promising candidates for point-of-care or at-home usage; if paired with a health status questionnaire, the assessment of the immune system status becomes solid and we demonstrated potentials for promoting the assessment tool with data mining techniques. [ABSTRACT FROM AUTHOR]

Since the introduction of paper-based analytical devices as potential diagnostic platforms a few decades ago, huge efforts have been made in this field to develop systems suitable for meeting the requirements for the point-of-care (POC) approach. Considerable progress has been achieved in the adaptation of existing analysis methods to a paper-based format, especially considering the chemiluminescent (CL)-immunoassays-based techniques. The implementation of biospecific assays with CL detection and paper-based technology represents an ideal solution for the development of portable analytical devices for on-site applications, since the peculiarities of these features create a unique combination for fitting the POC purposes. Despite this, the scientific production is not paralleled by the diffusion of such devices into everyday life. This review aims to highlight the open issues that are responsible for this discrepancy and to find the aspects that require a focused and targeted research to make these methods really applicable in routine analysis. [ABSTRACT FROM AUTHOR]

Paper-based lateral-flow immunoassays (LFIAs) have achieved considerable commercial success and their impact in diagnostics is continuously growing. LFIA results are often obtained by visualizing by the naked eye color changes in given areas, providing a qualitative information about the presence/absence of the target analyte in the sample. However, this platform has the potential to provide ultrasensitive quantitative analysis for several applications. Indeed, LFIA is based on well-established immunological techniques, which have known in the last year great advances due to the combination of highly sensitive tracers, innovative signal amplification strategies and last-generation instrumental detectors. All these available progresses can be applied also to the LFIA platform by adapting them to a portable and miniaturized format. This possibility opens countless strategies for definitively turning the LFIA technique into an ultrasensitive quantitative method. Among the different proposals for achieving this goal, the use of enzyme-based immunoassay is very well known and widespread for routine analysis and it can represent a valid approach for improving LFIA performances. Several examples have been recently reported in literature exploiting enzymes properties and features for obtaining significative advances in this field. In this review, we aim to provide a critical overview of the recent progresses in highly sensitive LFIA detection technologies, involving the exploitation of enzyme-based amplification strategies. The features and applications of the technologies, along with future developments and challenges, are also discussed. [ABSTRACT FROM AUTHOR]

A novel self-powered point-of-care low-power electronics approach for galvanic cell-based sample concentration measurement is presented. The electronic system harvests and senses at the same time from the single cell. The system implements a solution that is suitable in those scenarios where extreme low power is generated from the fuel cell. The proposed approach implements a capacitive-based method to perform a non-linear sweep voltammetry to the cell, but without the need to implement a potentiostat amplifier for that purpose. It provides a digital-user readable result without the need for external non-self-powered devices or instruments compared with other solutions. The system conception was validated for a particular case. The scenario consisted of the measurement of a NaCl solution as the electrolyte, which was related to the conductivity of the sample. The electronic reader continuously measured the current with a transfer function gain of 1.012 V m A −1. The overall system exhibited a maximum coefficient of variation of 6.1 %, which was an improvement compared with the state-of-the-art. The proof of concept of this electronics system was validated with a maximum power consumption of 5.8 μ W using commercial-off-the-self parts. [ABSTRACT FROM AUTHOR]

Point-of-care ultrasound (POCUS), realized by recent developments in portable ultrasound imaging systems for prompt diagnosis and treatment, has become a major tool in accidents or emergencies. Concomitantly, the number of untrained/unskilled staff not familiar with the operation of the ultrasound system for diagnosis is increasing. By providing an imaging guide to assist clinical decisions and support diagnosis, the risk brought by inexperienced users can be managed. Recently, deep learning has been employed to guide users in ultrasound scanning and diagnosis. However, in a cloud-based ultrasonic artificial intelligence system, the use of POCUS is limited due to information security, network integrity, and significant energy consumption. To address this, we propose (1) a structure that simultaneously provides ultrasound imaging and a mobile device-based ultrasound image guide using deep learning, and (2) a reverse scan conversion (RSC) method for building an ultrasound training dataset to increase the accuracy of the deep learning model. Experimental results show that the proposed structure can achieve ultrasound imaging and deep learning simultaneously at a maximum rate of 42.9 frames per second, and that the RSC method improves the image classification accuracy by more than 3%. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) can serve as biochemical markers of various pathologies like liver disfunction and poisonings by nerve agents. Ellman's assay is the standard spectrophotometric method to measure cholinesterase activity in clinical laboratories. The authors present a new colorimetric test to assess AChE and BChE activity in biological samples using chromogenic reagents, treated 3D-printed measuring pads and a smartphone camera as a signal detector. Multiwell pads treated with reagent substrates 2,6-dichlorophenolindophenyl acetate, indoxylacetate, ethoxyresorufin and methoxyresorufin were prepared and tested for AChE and BChE. In the experiments, 3D-printed pads containing indoxylacetate as a chromogenic substrate were optimal for analytical purposes. The best results were achieved using the red (R) channel, where the limit of detection was 4.05 µkat/mL for BChE and 4.38 µkat/mL for AChE using a 40 µL sample and a 60 min assay. The major advantage of this method is its overall simplicity, as samples are applied directly without any specific treatment or added reagents. The assay was also validated to the standard Ellman's assay using human plasma samples. In conclusion, this smartphone camera-based colorimetric assay appears to have practical applicability and to be a suitable method for point-of-care testing because it does not require specific manipulation, additional education of staff or use of sophisticated analytical instruments. [ABSTRACT FROM AUTHOR]

The demand for point-of-need (PON) diagnostics for clinical and other applications is continuing to grow. Much of this demand is currently serviced by biosensors, which combine a bioanalytical sensing element with a transducing device that reports results to the user. Ideally, such devices are easy to use and do not require special skills of the end user. Application-dependent, PON devices may need to be capable of measuring low levels of analytes very rapidly, and it is often helpful if they are also portable. To date, only two transduction modalities, colorimetric lateral flow immunoassays (LFIs) and electrochemical assays, fully meet these requirements and have been widely adopted at the point-of-need. These modalities are either non-quantitative (LFIs) or highly analyte-specific (electrochemical glucose meters), therefore requiring considerable modification if they are to be co-opted for measuring other biomarkers. Förster Resonance Energy Transfer (RET)-based biosensors incorporate a quantitative and highly versatile transduction modality that has been extensively used in biomedical research laboratories. RET-biosensors have not yet been applied at the point-of-need despite its advantages over other established techniques. In this review, we explore and discuss recent developments in the translation of RET-biosensors for PON diagnoses, including their potential benefits and drawbacks. [ABSTRACT FROM AUTHOR]

The differential count of white blood cells (WBCs) is one widely used approach to assess the status of a patient's immune system. Currently, the main methods of differential WBC counting are manual counting and automatic instrument analysis with labeling preprocessing. But these two methods are complicated to operate and may interfere with the physiological states of cells. Therefore, we propose a deep learning-based method to perform label-free classification of three types of WBCs based on their morphologies to judge the activated or inactivated neutrophils. Over 90% accuracy was finally achieved by a pre-trained fine-tuning Resnet-50 network. This deep learning-based method for label-free WBC classification can tackle the problem of complex instrumental operation and interference of fluorescent labeling to the physiological states of the cells, which is promising for future point-of-care applications. [ABSTRACT FROM AUTHOR]

Biosensors are measurement devices that can sense several biomolecules, and are widely used for the detection of relevant clinical pathogens such as bacteria and viruses, showing outstanding results. Because of the latent existing risk of facing another pandemic like the one we are living through due to COVID-19, researchers are constantly looking forward to developing new technologies for diagnosis and treatment of infections caused by different bacteria and viruses. Regarding that, nanotechnology has improved biosensors' design and performance through the development of materials and nanoparticles that enhance their affinity, selectivity, and efficacy in detecting these pathogens, such as employing nanoparticles, graphene quantum dots, and electrospun nanofibers. Therefore, this work aims to present a comprehensive review that exposes how biosensors work in terms of bacterial and viral detection, and the nanotechnological features that are contributing to achieving a faster yet still efficient COVID-19 diagnosis at the point-of-care. [ABSTRACT FROM AUTHOR]

Interferon-gamma (IFN-γ) is a cytokine associated with inflammatory diseases, virus, infection, etc. The quantification of interferon-gamma concentration levels is studied to relate the immune system response to the progression of disease. In this work, we used a label-free point-of-care device based on the increase relative optical power (IROP) and a biosensor based on photonic transducers called BICELLs (Biophotonic Sensing Cells) to evaluate interferon-gamma concentrations. The BICELLs' sensing surface size used is 100 μm in diameter. The bioreceptor is attached to the surface by streptavidin-biotin affinity. This label-free IROP-based device can work with a low concentration of reagents and a low sample volume for measurements. Furthermore, this new device was compared with an ELISA technique in the same conditions. A good correlation was achieved between both techniques. This device is easy to use, and it is a cost-effective tool for monitoring an analyte in a disease. [ABSTRACT FROM AUTHOR]

Population extended life expectancy has significantly increased the risk of septic shock in an ageing population. Sepsis affects roughly 20 million people every year, resulting in over 11 million deaths. The need for faster more accurate diagnostics and better management is therefore paramount in the fight to prevent these avoidable deaths. Here we report the development of a POC device with the ability to identify a broad range of pathogens on a lateral flow platform. Namely Gram-positive and Gram-negative bacteria. The simple to use laboratory device has the potential to be automated, thus enabling an operator to carry out solid-phase lysis and room temperature RPA in situ, providing accurate results in hours rather than days. Results show there is a potential for a fully automated device in which concepts described in this paper can be integrated into a lateral flow device. [ABSTRACT FROM AUTHOR]

Glycine monitoring is gaining importance as a biomarker in clinical analysis due to its involvement in multiple physiological functions, which results in glycine being one of the most analyzed biomolecules for diagnostics. This growing demand requires faster and more reliable, while affordable, analytical methods that can replace the current gold standard for glycine detection, which is based on sample extraction with subsequent use of liquid chromatography or fluorometric kits for its quantification in centralized laboratories. This work discusses electrochemical sensors and biosensors as an alternative option, focusing on their potential application for glycine determination in blood, urine, and cerebrospinal fluid, the three most widely used matrices for glycine analysis with clinical meaning. For electrochemical sensors, voltammetry/amperometry is the preferred readout (10 of the 13 papers collected in this review) and metal-based redox mediator modification is the predominant approach for electrode fabrication (11 of the 13 papers). However, none of the reported electrochemical sensors fulfill the requirements for direct analysis of biological fluids, most of them lacking appropriate selectivity, linear range of response, and/or capability of measuring at physiological conditions. Enhanced selectivity has been recently reported using biosensors (with an enzyme element in the electrode design), although this is still a very incipient approach. Currently, despite the benefits of electrochemistry, only optical biosensors have been successfully reported for glycine detection and, from all the inspected works, it is clear that bioengineering efforts will play a key role in the embellishment of selectivity and storage stability of the sensing element in the sensor. [ABSTRACT FROM AUTHOR]

The demand for wearable and point-of-care devices has led to an increase in electrochemical sensor development to measure an ever-increasing array of biological molecules. In order to move from the benchtop to truly portable devices, the development of new biosensors requires miniaturized instrumentation capable of making highly sensitive amperometric measurements. To meet this demand, we have developed KickStat, a miniaturized potentiostat that combines the small size of the integrated Texas Instruments LMP91000 potentiostat chip (Texas Instruments, Dallas, TX, USA) with the processing power of the ARM Cortex-M0+ SAMD21 microcontroller (Microchip Technology, Chandler, AZ, USA) on a custom-designed 21.6 mm by 20.3 mm circuit board. By incorporating onboard signal processing via the SAMD21, we achieve 1 mV voltage increment resolution and an instrumental limit of detection of 4.5 nA in a coin-sized form factor. This elegant engineering solution allows for high-resolution electrochemical analysis without requiring extensive circuitry. We measured the faradaic current of an anti-cocaine aptamer using cyclic voltammetry and square wave voltammetry and demonstrated that KickStat's response was within 0.6% of a high-end benchtop potentiostat. To further support others in electrochemical biosensors development, we have made KickStat's design and firmware available in an online GitHub repository. [ABSTRACT FROM AUTHOR]

Point-of-care (PoC) diagnostics is promising for early detection of a number of diseases, including cancer, diabetes, and cardiovascular diseases, in addition to serving for monitoring health conditions. To be efficient and cost-effective, portable PoC devices are made with microfluidic technologies, with which laboratory analysis can be made with small-volume samples. Recent years have witnessed considerable progress in this area with "epidermal electronics", including miniaturized wearable diagnosis devices. These wearable devices allow for continuous real-time transmission of biological data to the Internet for further processing and transformation into clinical knowledge. Other approaches include bluetooth and WiFi technology for data transmission from portable (non-wearable) diagnosis devices to cellphones or computers, and then to the Internet for communication with centralized healthcare structures. There are, however, considerable challenges to be faced before PoC devices become routine in the clinical practice. For instance, the implementation of this technology requires integration of detection components with other fluid regulatory elements at the microscale, where fluid-flow properties become increasingly controlled by viscous forces rather than inertial forces. Another challenge is to develop new materials for environmentally friendly, cheap, and portable microfluidic devices. In this review paper, we first revisit the progress made in the last few years and discuss trends and strategies for the fabrication of microfluidic devices. Then, we discuss the challenges in lab-on-a-chip biosensing devices, including colorimetric sensors coupled to smartphones, plasmonic sensors, and electronic tongues. The latter ones use statistical and big data analysis for proper classification. The increasing use of big data and artificial intelligence methods is then commented upon in the context of wearable and handled biosensing platforms for the Internet of things and futuristic healthcare systems. [ABSTRACT FROM AUTHOR]

In healthcare, new diagnostic tools that help in the diagnosis, prognosis, and monitoring of diseases rapidly and accurately are in high demand. For in-situ measurement of disease or infection biomarkers, point-of-care devices provide a dramatic speed advantage over conventional techniques, thus aiding clinicians in decision-making. During the last decade, paper-based analytical devices, combining paper substrates and electrochemical detection components, have emerged as important point-of-need diagnostic tools. This review highlights significant works on this topic over the last five years, from 2015 to 2019. The most relevant articles published in 2018 and 2019 are examined in detail, focusing on device fabrication techniques and materials applied to the production of paper fluidic and electrochemical cell architectures as well as on the final device assembly. Two main approaches were identified, that are, on one hand, those ones where the fabrication of the electrochemical cell is done on the paper substrate, where the fluidic structures are also defined, and, on the other hand, the fabrication of those ones where the electrochemical cell and liquid-driving paper component are defined on different substrates and then heterogeneously assembled. The main limitations of the current technologies are outlined and an outlook on the current technology status and future prospects is given. [ABSTRACT FROM AUTHOR]

During open-heart surgery, the status of hemostasis has to be constantly monitored to quickly and reliably detect bleeding or coagulation disorders. In this study, a novel optimized piezo-based measuring system (PIEZ) for rheological monitoring of hemostasis was established. The applicability of the PIEZ for the evaluation of nucleic acid-based drugs influencing coagulation was analyzed. Thrombin aptamers such as NU172 might be used during extracorporeal circulation (ECC) in combination with a reduced heparin concentration or for patients with heparin-induced thrombocytopenia (HIT). Therefore, the effect of the coagulation inhibiting thrombin aptamer NU172 and the abrogation by its complementary antidote sequence (AD) were investigated by this rheological PIEZ system. After the addition of different NU172 concentrations, the coagulation of fresh human blood was analyzed under static conditions and using an in vitro rotation model under dynamic conditions (simulating ECC). The clotting times (CTs) detected by PIEZ were compared to those obtained with a medical reference device, a ball coagulometer. Additionally, after the circulation of blood samples for 30 min at 37 °C, blood cell numbers, thrombin markers (thrombin-antithrombin III (TAT) and fibrinopeptide A (FPA)) and a platelet activation marker (β-thromboglobulin (β-TG)) were analyzed by enzyme-linked immunosorbent assays (ELISAs). The increase of NU172 concentration resulted in prolonged CTs, which were comparable between the reference ball coagulometer and the PIEZ, demonstrating the reliability of the new measuring system. Moreover, by looking at the slope of the linear regression of the viscous and elastic components, PIEZ also could provide information on the kinetics of the coagulation reaction. The shear viscosity at the end of the measurements (after 300 s) was indicative of clot firmness. Furthermore, the PIEZ was able to detect the abrogation of coagulation inhibition after the equimolar addition of NU172 aptamer´s AD. The obtained results showed that the established PIEZ is capable to dynamically measure the hemostasis status in whole blood and can be applied to analyze nucleic acid-based drugs influencing the coagulation. [ABSTRACT FROM AUTHOR]

The detection and analysis of circulating tumor cells (CTCs) plays a crucial role in clinical practice. However, the heterogeneity and rarity of CTCs make their capture and separation from peripheral blood very difficult while maintaining their structural integrity and viability. We previously demonstrated the effectiveness of the Magnetic Cell Centrifuge Platform (MCCP), which combined the magnetic-labeling cell separation mechanism with the size-based method. In this paper, a comparison of the effectiveness of different microsieve pore geometries toward MCCP is demonstrated to improve the yield of the target cell capture. Firstly, models of a trapped cell with rectangular and circular pore geometries are presented to compare the contact force using finite element numerical simulations. The device performance is then evaluated with both constant pressure and constant flow rate experimental conditions. In addition, the efficient isolation of magnetically labeled Hela cells with red fluorescent proteins (target cells) from Hela cells with green fluorescent protein (background cells) is validated. The experimental results show that the circular sieves yield 97% purity of the target cells from the sample with a throughput of up to 2 μL/s and 66-fold sample enrichment. This finding will pave the way for the design of a higher efficient MCCP systems. [ABSTRACT FROM AUTHOR]

Rather than the internal genome nucleic acids, the biomolecules on the surface of the influenza virus itself should be detected for a more exact and rapid point-of-care yes/no decision for influenza virus-induced infectious diseases. This work demonstrates the ultrasensitive electrical detection of the HA1 domain of hemagglutinin (HA), a representative viral surface protein of the influenza virus, using the top-down complementary metal oxide semiconductor (CMOS) processed silicon nanowire (SiNW) field-effect transistor (FET) configuration. Cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-NANA) was employed as a probe that specifically binds both to the aldehyde self-aligned monolayer on the SiNWs and to HA1 simultaneously. CMP-NANA was serially combined with two kinds of linkers, namely 3-aminopropyltriethoxysilane and glutaraldehyde. The surface functionalization used was verified using the purification of glutathione S-transferase-tagged HA1, contact angle measurement, enzyme-linked immunosorbent assay test, and isoelectric focusing analysis. The proposed functionalized SiNW FET showed high sensitivities of the threshold voltage shift (ΔVT) ~51 mV/pH and the ΔVT = 112 mV (63 mV/decade) with an ultralow detectable range of 1 fM of target protein HA1. [ABSTRACT FROM AUTHOR]

Molecular imprinting is a rapidly growing area of interest involving the synthesis of artificial recognition elements that enable the separation of analyte from a sample matrix and its determination. Traditionally, this approach can be successfully applied to small analyte (<1.5 kDa) separation/ extraction, but, more recently it is finding utility in biomimetic sensors. These sensors consist of a recognition element and a transducer similar to their biosensor counterparts, however, the fundamental distinction is that biomimetic sensors employ an artificial recognition element. Molecularly imprinted polymers (MIPs) employed as the recognition elements in biomimetic sensors contain binding sites complementary in shape and functionality to their target analyte. Despite the growing interest in molecularly imprinting techniques, the commercial adoption of this technology is yet to be widely realised for blood sample analysis. This review aims to assess the applicability of this technology for the point-of-care testing (POCT) of cardiovascular disease-related biomarkers. More specifically, molecular imprinting is critically evaluated with respect to the detection of cardiac biomarkers indicative of acute coronary syndrome (ACS), such as the cardiac troponins (cTns). The challenges associated with the synthesis of MIPs for protein detection are outlined, in addition to enhancement techniques that ultimately improve the analytical performance of biomimetic sensors. The mechanism of detection employed to convert the analyte concentration into a measurable signal in biomimetic sensors will be discussed. Furthermore, the analytical performance of these sensors will be compared with biosensors and their potential implementation within clinical settings will be considered. In addition, the most suitable application of these sensors for cardiovascular assessment will be presented. [ABSTRACT FROM AUTHOR]

Surface-plasmon-resonance (SPR) is a quantum-electromagnetic phenomenon arising from the interaction of light with free electrons at a metal-dielectric interface. At a specific angle/wavelength of light, the photon's energy is transferred to excite the oscillation of the free electrons on the surface. A change in the refractive-index (RI) may occur, which is influenced by the analyte concentration in the medium in close contact with the metal surface. SPR has been widely used for the detection of gaseous, liquid, or solid samples. In this study, a functionalized specific SPR chip was designed and used in a novel point-of-care SPR module (PhotonicSys SPR H5) for the detection of the stroke biomarkers NT-proBNP and S100β. These biomarkers have proven to be good for stroke diagnosis, with sensitivity and specificity of >85%. Specific detection was done by binding a biomolecular-recognizing antibody onto the Au SPR-chip. Detection was tested in water and plasma samples. NT-proBNP and S100β were detected in a range of concentrations for stroke, from 0.1 ng/mL to 10 ng/mL. The RI of the blank plasma samples was 1.362412, and the lowest concentration tested for both biomarkers showed a prominent shift in the RI signal (0.25 ng/mL NT-proBNP (1.364215) and S100β (1.364024)). The sensor demonstrated a clinically relevant limit-of-detection of less than ng/mL. [ABSTRACT FROM AUTHOR]