Multiplex sensing of IL-10 and CRP towards predicting critical illness in COVID-19 infections.

Here we present a sensitive method for the detection and quantification of two (IL -10 and CRP) immuno-responsive biomarkers in various biofluids. The significance of these immune response biomarkers lies in them displaying elevated levels in critically ill COVID -19 patients. The developed electrochemical sensor contains a gold film electrode with ZnO nanoparticles deposited on its surface to increase the surface area of the working electrode while integrating antibody-antigen interactions into the detection system. This multiplex biosensor has a wide linear range from 0.01 µg/mL to 100 µg/mL and 0.1 pg/mL to 1000 pg/mL for CRP and IL10, respectively. The cross-reactivity of this multiplex sensor platform was evaluated between these two proteins and was <20%. Recovery studies were performed by spiking known concentrations in serum and urine samples. The recovery was calculated and ranged from 80% to 100%, confirming clinical applicability. This electrochemical sensing platform can aid in the early screening of COVID -19 patients to monitor for the development of more serious and potentially lethal symptoms.

Emerging Electrochemical Biosensing Trends for Rapid Diagnosis of COVID-19 Biomarkers as Point-of-Care Platforms: A Critical Review.

Rapid diagnosis is a critical aspect associated with controlling the spread of COVID-19. Electrochemical sensor platforms are ideally suited for rapid and highly sensitive detection of biomolecules. This review focuses on state-of-the-art of COVID-19 biomarker detection by utilizing electrochemical biosensing platforms. Point-of-care (POC) sensing is one of the most promising and emerging fields in detecting and quantifying health biomarkers. Electrochemical biosensors play a major role in the development of point-of-care devices because of their high sensitivity, specificity, and ability for rapid analysis. Integration of electrochemistry with point-of-care technologies in the context of COVID-19 diagnosis and screening has facilitated in convenient operation, miniaturization, and portability. Identification of potential biomarkers in disease diagnosis is crucial for patient monitoring concerning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we will discuss the choice of biomarkers in addition to the various types of electrochemical sensors that have been developed to meet the needs of rapid detection and disease severity analysis.

Simultaneous detection of sepsis host response biomarkers in whole blood using electrochemical biosensor.

Sepsis is a silent killer, caused by a syndromic reaction of the body's immune system to an infection that is typically the ultimate pathway to mortality due to numerous infectious diseases, including COVID-19 across the world. In the United States alone, sepsis claims 220,000 lives, with a dangerously high fatality rate between 25% and 50%. Early detection and treatment can avert 80% of sepsis mortality which is currently unavailable in most healthcare institutions. The novelty in this work is the ability to simultaneously detect eight (IL-6, IL-8, IL-10, IP-10, TRAIL, d-dimer, CRP, and G-CSF) heterogeneous immune response biomarkers directly in whole blood without the need for dilution or sample processing. The DETecT sepsis (Direct Electrochemical Technique Targeting Sepsis) 2.0 sensor device leverages electrochemical impedance spectroscopy as a technique to detect subtle binding interactions at the metal/semi-conductor sensor interface and reports results within 5 min using only two drops (~100 µl) of blood. The device positively (r >0.87) correlated with lab reference standard LUMINEX for clinical translation using 40 patient samples. The developed device showed diagnostic accuracy greater than 80% (AUC >0.8) establishing excellent specific and sensitive response. Portable handheld user-friendly feature coupled with precise quantification of immune biomarkers makes the device amenable in a versatile setting providing insights on patient's immune response. This work highlights an innovative solution of enhancing sepsis care and management in the absence of a decision support device in the continuum of sepsis care.

Tracking metabolic responses based on macronutrient consumption: A comprehensive study to continuously monitor and quantify dual markers (cortisol and glucose) in human sweat using WATCH sensor.

Wearable Awareness Through Continuous Hidrosis (WATCH) sensor is a sweat based monitoring platform that tracks cortisol and glucose for the purpose of understanding metabolic responses related to macronutrient consumption. In this research article, we have demonstrated the ability of tracking these two biomarkers in passive human sweat over a workday period (8 h) for 10 human subjects in conjunction with their macronutrient consumption. The validation of the WATCH sensor performance was carried out via standard reference methods such as Luminex and ELISA This is a first demonstration of a passive sweat sensing technology that can detect interrelated dual metabolites, cortisol, and glucose, on a single sensing platform. The significance of detecting the two biomarkers simultaneously is that capturing the body's metabolic and endocrinal responses to dietary triggers can lead to improved lifestyle management. For sweat cortisol, we achieved a detection limit of 1 ng/ml (range ∼1-12.5 ng/ml) with Pearson's "r" of 0.897 in reference studies and 0.868 in WATCH studies. Similarly, for sweat glucose, we achieved a detection limit of 1 mg/dl (range ∼ 1-11 mg/dl) with Pearson's "r" of 0.968 in reference studies and 0.947 in WATCH studies, respectively. The statistical robustness of the WATCH sensor was established through the Bland-Altman analysis, whereby the sweat cortisol and sweat glucose levels are comparable to the standard reference method. The probability distribution (t-test), power analysis (power 0.82-0.87), α = 0.05. Mean absolute relative difference (MARD) outcome of Ë·5.10-5.15% further confirmed the statistical robustness of the sweat sensing WATCH device output.

Temporal profiling of cytokines in passively expressed sweat for detection of infection using wearable device.

This work presents the viability of passive eccrine sweat as a functional biofluid toward tracking the human body's inflammatory response. Cytokines are biomarkers that orchestrate the manifestation and progression of an infection/inflammatory event. Hence, noninvasive, real-time monitoring of cytokines can be pivotal in assessing the progression of infection/inflammatory event, which may be feasible through monitoring of host immune markers in eccrine sweat. This work is the first experimental proof demonstrating the ability to detect inflammation/infection such as fever, FLU directly from passively expressed sweat in human subjects using a wearable "SWEATSENSER" device. The developed SWEATSENSER device demonstrates stable, real-time monitoring of inflammatory cytokines in passive sweat. An accuracy of >90% and specificity >95% was achieved using SWEATSENSER for a panel of cytokines (interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) over an analytical range of 0.2-200 pg mL-1. The SWEATSENSER demonstrated a correlation of Pearson's r > 0.98 for the study biomarkers in a cohort of 26 subjects when correlated with standard reference method. Comparable IL-8 levels (2-15 pg mL-1) between systemic circulation (serum) and eccrine sweat through clinical studies in a cohort of 15 subjects, and the ability to distinguish healthy and sick (infection) cohort using inflammatory cytokines in sweat provides pioneering evidence of the SWEATSENSER technology for noninvasive tracking of host immune response biomarkers. Such a wearable device can offer significant strides in improving prognosis and provide personalized therapeutic treatment for several inflammatory/infectious diseases.

Evidence-based point-of-care technology development during the COVID-19 pandemic.

Since December 2019, the SARS-CoV-2 outbreak that began in Wuhan, China has spread to nearly every continent and become a global health concern. Although much has been discovered about COVID-19 and its pathogenesis, the WHO has identified an immediate need to increase the levels of testing for COVID-19 and identify the stages of the disease accurately for appropriate action to be taken by clinicians and emergency care units. Harnessing technology for accurate diagnosis and staging will improve patient outcomes and minimize serious consequences of false-positive test results. Point-of-care technologies aim to intervene at every stage of the disease to quickly identify infected patients and asymptomatic carriers and stratify them for timely treatment. This requires the tests to be rapid, accurate, sensitive, simple to use and compatible with many body fluids. Mobile platforms are optimal for remote, small-scale deployment, whereas facility-based platforms at hospital centers and laboratory settings offer higher throughput. Here we review evidence-based point-of-care technologies in the context of the entire continuum of COVID-19, from early screening to treatment, and discuss their impact on improving patient outcomes.