Electrochemical Immunoassay for Capturing Capsular Polysaccharide of Burkholderia pseudomallei: Early Onsite Detection of Melioidosis.

This study presented the detection and quantification of capsular polysaccharide (CPS) as a biomarker for the diagnosis of melioidosis. After successfully screening four monoclonal antibodies (mAbs) previously determined to bind CPS molecules, the team developed a portable electrochemical immunosensor based on antibody-antigen interactions. The biosensor was able to detect CPS with a wide detection range from 0.1pg/mL to 1 µg/mL. The developed biosensor achieved high sensitivity for the detection of CPS spiked into both urine and serum. The developed assay platform was successfully programmed into a Windows app, and the sensor performance was evaluated with different spiked concentrations. The rapid electro-analytical device (READ) sensor showed great unprecedented sensitivity for the detection of CPS molecules in both serum and urine, and results were cross-validated with ELISA methods.

Continuous Monitoring of CRP, IL-6, and Calprotectin in Inflammatory Bowel Disease Using a Perspiration-Based Wearable Device.

BACKGROUND: Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration. METHODS: Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed. RESULTS: A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69 ng/mL; active 95% confidence interval [CI], 466.0-1833 ng/mL; remission 95% CI, 328.4-950.8 ng/mL), serum (median = 1860.82 ng/mL; active 95% CI, 1705-2985 ng/mL; remission 95% CI, 870.2-1786 ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums. CONCLUSIONS: We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.

This work establishes the clinical utility of perspiration as a noninvasive, continuous marker for gut inflammation and demonstrates the ability to distinguish between active and inactive inflammatory bowel disease across perspiration, serum, and stool.

PathoSense: a rapid electroanalytical device platform for screening Salmonella in water samples.

Salmonella contamination is a major global health challenge, causing significant foodborne illness. However, current detection methods face limitations in sensitivity and time, which mostly rely on the culture-based detection techniques. Hence, there is an immediate and critical need to enhance early detection, reduce the incidence and impact of Salmonella contamination resulting in outbreaks. In this work, we demonstrate a portable non-faradaic, electrochemical sensing platform capable of detecting Salmonella in potable water with an assay turnaround time of ~ 9 min. We evaluated the effectiveness of this sensing platform by studying two sensor configurations: one utilizing pure gold (Au) and the other incorporating a semiconductor namely a zinc oxide thin film coated on the surface of the gold (Au/ZnO). The inclusion of zinc oxide was intended to enhance the sensing capabilities of the system. Through comprehensive experimentation and analysis, the LoD (limit of detection) values for the Au sensor and Au/ZnO sensor were 0.9 and 0.6 CFU/mL, respectively. In addition to sensitivity, we examined the sensing platform's precision and reproducibility. Both the Au sensor and Au/ZnO sensor exhibited remarkable consistency, with inter-study percentage coefficient of variation (%CV) and intra-study %CV consistently below 10%. The proposed sensing platform exhibits high sensitivity in detecting low concentrations of Salmonella in potable water. Its successful development demonstrates its potential as a rapid and on-site detection tool, offering portability and ease of use. This research opens new avenues for electrochemical-based sensors in food safety and public health, mitigating Salmonella outbreaks and improving water quality monitoring.

Characterization of an In-Situ Soil Organic Carbon (SOC) via a Smart-Electrochemical Sensing Approach.

Soil is a vital component of the ecosystem that drives the holistic homeostasis of the environment. Directly, soil quality and health by means of sufficient levels of soil nutrients are required for sustainable agricultural practices for ideal crop yield. Among these groups of nutrients, soil carbon is a factor which has a dominating effect on greenhouse carbon phenomena and thereby the climate change rate and its influence on the planet. It influences the fertility of soil and other conditions like enriched nutrient cycling and water retention that forms the basis for modern 'regenerative agriculture'. Implementation of soil sensors would be fundamentally beneficial to characterize the soil parameters in a local as well as global environmental impact standpoint, and electrochemistry as a transduction mode is very apt due to its feasibility and ease of applicability. Organic Matter present in soil (SOM) changes the electroanalytical behavior of moieties present that are carbon-derived. Hence, an electrochemical-based 'bottom-up' approach is evaluated in this study to track soil organic carbon (SOC). As part of this setup, soil as a solid-phase electrolyte as in a standard electrochemical cell and electrode probes functionalized with correlated ionic species on top of the metalized electrodes are utilized. The surficial interface is biased using a square pulsed charge, thereby studying the effect of the polar current as a function of the SOC profile. The sensor formulation composite used is such that materials have higher capacity to interact with organic carbon pools in soil. The proposed sensor platform is then compared against the standard combustion method for SOC analysis and its merit is evaluated as a potential in situ, on-demand electrochemical soil analysis platform.

Longitudinal assessment of sweat-based TNF-alpha in inflammatory bowel disease using a wearable device.

Wearable devices can non-invasively monitor patients with chronic diseases. Sweat is an easily accessible biofluid for continuous sampling of analytes, including inflammatory markers and cytokines. We evaluated a sweat sensing wearable device in subjects with and without inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract. Participants with an IBD related hospital admission and a C-reactive protein level above 5 mg/L wore a sweat sensing wearable device for up to 5 days. Tumor necrosis factor-alpha (TNF-α) levels were continually assessed in the sweat via the sensor, and daily in the blood. A second cohort of healthy subjects without chronic diseases wore the device for up to 48 h. Twenty-eight subjects were enrolled. In the 16 subjects with IBD, a moderate linear relationship between serum and sweat TNF-α levels was observed (R2 = 0.72). Subjects with IBD were found to have a mean sweat TNF-α level of 2.11 pg/mL, compared to a mean value of 0.19 pg/mL in 12 healthy controls (p < 0.0001). Sweat TNF-α measurements differentiated subjects with active IBD from healthy subjects with an AUC of 0.962 (95% CI 0.894-1.000). A sweat sensing wearable device can longitudinally measure key sweat-based markers of IBD. TNF-α levels in the sweat of subjects with IBD correlate with serum values, suggesting feasibility in non-invasive disease monitoring.

Longitudinal monitoring of IL-6 and CRP in inflammatory bowel disease using IBD-AWARE.

There are limitations to monitoring modalities for chronic inflammatory conditions, including inflammatory bowel disease (IBD). Wearable devices are scalable mobile health technology that present an opportunity to monitor markers that have been linked to worsening, chronic inflammatory conditions and enable remote monitoring. In this research article, we evaluate and demonstrate a proof-of-concept wearable device to longitudinally monitor inflammatory and immune markers linked to IBD disease activity in sweat compared to expression in serum. Sixteen participants with an IBD-related hospital admission and a C-reactive protein (CRP) > 5 µg/mL were followed for up to 5 days. The sweat sensing device also known as IBD AWARE was worn to continuously measure CRP and interleukin-6 (IL-6) in the sweat of participants via electrochemical impedance spectroscopy. Serum samples were collected daily. A linear relationship between serum and sweat readings for CRP and IL-6 was demonstrated based on individual linear correlation coefficients. Pooled CRP and IL-6 serum-to-sweat ratios demonstrated improving correlation coefficients as serum cutoffs decreased. Between the first and last day of observation, significant and non-significant trends in serum CRP and IL-6 were observed in the sweat. Comparison of sweat measurements between the subjects with active IBD and 10 healthy subjects distinguished an inflamed and uninflamed state with an AUC of 0.85 (95% CI: 0.68-1.00) and a sensitivity and specificity of 82% and 70% at a CRP cutoff of 938.9 pg/mL. IBD AWARE wearable device holds promise in longitudinally monitoring individuals with IBD and other inflammatory diseases.

Passive sweat wearable: A new paradigm in the wearable landscape toward enabling "detect to treat" opportunities.

Growing interest over recent years in personalized health monitoring coupled with the skyrocketing popularity of wearable smart devices has led to the increased relevance of wearable sweat-based sensors for biomarker detection. From optimizing workouts to risk management of cardiovascular diseases and monitoring prediabetes, the ability of sweat sensors to continuously and noninvasively measure biomarkers in real-time has a wide range of applications. Conventional sweat sensors utilize external stimulation of sweat glands to obtain samples, however; this stimulation influences the expression profile of the biomarkers and reduces the accuracy of the detection method. To address this limitation, our laboratory pioneered the development of the passive sweat sensor subfield, which allowed for our progress in developing a sweat chemistry panel. Passive sweat sensors utilize nanoporous structures to confine and detect biomarkers in ultra-low sweat volumes. The ability of passive sweat sensors to use smaller samples than conventional sensors enable users with sedentary lifestyles who perspire less to benefit from sweat sensor technology not previously afforded to them. Herein, the mechanisms and strategies of current sweat sensors are summarized with an emphasis on the emerging subfield of passive sweat-based diagnostics. Prospects for this technology include discovering new biomarkers expressed in sweat and expanding the list of relevant detectable biomarkers. Moreover, the accuracy of biomarker detection can be enhanced with machine learning using prediction algorithms trained on clinical data. Applying this machine learning in conjunction with multiplex biomarker detection will allow for a more holistic approach to trend predictions. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.

Naloxone-AuNPs@ZIF-8-Based Impedimetric Sensor Platform for Ultrasensitive Detection of Fentanyl and Fabrication of Fen-Track Prototype for Real-Field Analysis.

Opioids are considered to be a global threat, and we are facing the worst opioid crisis of the decade. Synthetic opioids like fentanyl are highly potent and deadly toward human body, and hence its detection is an inevitable requirement globally. Naloxone is known for its antagonist property toward fentanyl, and we performed computational simulations to find their interactions and use this principle to build the first of a kind impedimetric sensor device, transduced by 3D-ZIF-8 with in situ encapsulated naloxone-gold nanoparticles. The probe is synthesized using a unique encapsulation strategy, thoroughly characterized by various physicochemical and microscopic tools. The sensor is highly selective toward fentanyl and can detect fentanyl up to 100 ppm in a synthetic sample. A prototype device is also built based on the synthetic calibration and applied to the spiked urine sample, and the performance is evaluated using statistical and machine learning tools.

Espial: Electrochemical Soil pH Sensor for In Situ Real-Time Monitoring.

We present a first-of-its-kind electrochemical sensor that demonstrates direct real-time continuous soil pH measurement without any soil pre-treatment. The sensor functionality, performance, and in-soil dynamics have been reported. The sensor coating is a composite matrix of alizarin and Nafion applied by drop casting onto the working electrode. Electrochemical impedance spectroscopy (EIS) and squarewave voltammetry (SWV) studies were conducted to demonstrate the functionality of each method in accurately detecting soil pH. The studies were conducted on three different soil textures (clay, sandy loam, and loamy clay) to cover the range of the soil texture triangle. Squarewave voltammetry showed pH-dependent responses regardless of soil texture (while electrochemical impedance spectroscopy's pH detection range was limited and dependent on soil texture). The linear models showed a sensitivity range from -50 mV/pH up to -66 mV/pH with R2 > 0.97 for the various soil textures in the pH range 3-9. The validation of the sensor showed less than a 10% error rate between the measured pH and reference pH for multiple different soil textures including ones that were not used in the calibration of the sensor. A 7-day in situ soil study showed the capability of the sensor to measure soil pH in a temporally dynamic manner with an error rate of less than 10%. The test was conducted using acidic and alkaline soils with pH values of 5.05 and 8.36, respectively.

E-SCAN: Electrochemical Scanning of Carbonates, an In Situ Approach for Screening and Quantifying Inorganic Carbon in Soil.

A modified three-electrode system was utilized with a correlated ion-capture film that is functional to changes in soil carbonate moieties to determine an understudied pool of soil carbon that is vital toward holistic carbon sequestration─carbonous soil minerals (CSM). This composite sensor was tested on soils with varying carbonate contents using cyclic voltammetry, chromatocoulometry (DC-based), and electrochemical impedance spectroscopy to determine signal output as a function of increasing dose. To determine the in-field capability, a portable potentiostat device was integrated into a probe head setup that could be inserted into soil for testing. The results from these experiments showed a linearity of R2 > 0.97 and a measurable sensing range from 0.01% (100 ppm) to 1% (10 000 ppm). Therefore, a first-of-a-kind in-soil sensor system was developed for determining carbonate content in real soil samples using electrochemistry that can be tested in-field to survey the field-deployable and point-of-use capability of the system.

Activated carbon derived from wood biochar for Amperometric sensing of Ammonia for early screening of chronic kidney disease.

Personalized medicine has emerged as an increasingly efficient and effective approach to addressing disease diagnosis and intervention. Ammonia is a waste product produced by the body during the digestion of protein. The requirement to develop an electrochemical sensing platform for monitoring skin ammonia levels holds great potential as an essential solution to pre-screen chronic kidney disease (CKD). In this research, we have manufactured an innovative electrochemical sensor by employing activated carbon derived from wood biochar as the signal transducer. We conducted a comprehensive analysis of the structural and morphological characteristics of the synthesized materials using various techniques. The hypothesized interaction was investigated using chronoamperometry as a transduction technique. To assess cross-reactivity, we conducted a study using common interferants or chemicals present in the environment. The data presented in this paper represents three replicates and is plotted with a 5 % error bar, demonstrating a 95 % confidence interval in the sensor response. In this study, we have elucidated the functionality and usefulness of a wearable microelectronic research prototype integrated with an HTC-activated carbon @RTIL-based electrochemical sensing platform for detecting ammonia levels released from the skin as a marker for chronic kidney disease screening. By enabling early detection and monitoring, these platforms can facilitate timely interventions, such as lifestyle modifications, medication adjustments, or referral to nephrology specialists. This proactive approach can potentially slow down disease progression, minimize the need for dialysis or transplantation, and ultimately improve the quality of life for CKD patients.

COVID severity test (CoST sensor)-An electrochemical immunosensing approach to stratify disease severity.

With the evolution of the COVID-19 pandemic, there is now a need for point-of-care devices for the quantification of disease biomarkers toward disease severity assessment. Disease progression has been determined as a multifactor phenomenon and can be treated based on the host immune response within each individual. CoST is an electrochemical immunosensor point-of-care device that can determine disease severity through multiplex measurement and quantification of spike protein, nucleocapsid protein, D-dimer, and IL-2R from 100 µL of plasma samples within a few minutes. The limit of detection was found to be 3 ng/mL and 21 ng/mL for S and N proteins whereas for D-dimer and IL-2R it was 0.0006 ng/mL and 0.242 ng/mL, respectively. Cross-reactivity of all the biomarkers was studied and it was found to be <20%. Inter and intra-assay variability of the CoST sensor was less than <15% confirming its ability to detect the target biomarker in body fluids. In addition, this platform has also been tested to quantify all four biomarkers in 40 patient samples and to predict the severity index. A significant difference was observed between healthy and COVID-19 samples with a p-value of 0.0002 for D-dimer and <0.0001 for other proteins confirming the ability of the COST sensor to be used as a point of care device to assess disease severity at clinical sites. This device platform can be modified to impact a wide range of disease indications where prognostic monitoring of the host response can be critical in modulating therapy.

MEASURE: Multiplex Exhaled Breath Condensate - Scanning Using Rapid Electro-Analytics.

Exhaled breath condensate is an emerging source of inflammatory biomarkers suitable for the noninvasive detection of respiratory disorders. Current gold standard methods are highly invasive and pose challenges in sample collection during airway inflammation monitoring. Cytokine biomarkers are detectable in EBC at increased or decreased concentrations. IL-6, IL-1ß, IL-8, and hs-CRP are characteristic biomarkers identified in respiratory disorders. We have demonstrated the promising outcomes of a 16-plexed electrochemical platform - READ 2.0 for the multiplexed detection of characteristic biomarkers in EBC. The sensor demonstrates dynamic ranges of 1-243 pg/mL with a lower detection limit of 1 pg/mL for IL-6 and IL-1ß, while the detection range and limit of detection for IL-8 and hs-CRP is 1-150 pg/mL and 3 pg/mL, respectively. The detection accuracies for the biomarkers are in the range of ∼85 ± 15% to ∼100 ± 10%. The sensor shows a nonspecific response to similar cross-reacting biomarkers. Analytical validation of the sensor with ELISA as the standard reference generated a correlation of R2 > 0.96 and mean biases of 10.9, 3.5, 17.4, and 3.9 pg/mL between the two methods for IL-6, IL-1ß, IL-8, and hs-CRP, respectively. The precision of the sensor in detecting low biomarker concentrations yields a %CV of <7%. The variation in the sensor's response on repeat EBC sample measurements and within a 6 h duration is less than 10%. The READ 2.0 platform shows a promise that EBC-based biomarker detection can prove to be vital in predicting the severity and survival rates of respiratory disorders and serve as a reference point for monitoring EBC-based biomarkers.

Recent Advances in Gas Detection Methodologies with a Special Focus on Environmental Sensing and Health Monitoring Applications─A Critical Review.

With the expansion of the Internet-of-Things (IoT), the use of gas sensors in the field of wearable technology, smart devices, and smart homes has increased manifold. These gas sensors have two key applications─one is the detection of gases present in the environment and the other is the detection of Volatile Organic Compounds (VOCs) that are found in the breath. In this review, we focus systematically on the advancements in the field of various spectroscopic methods such as mass spectrometry-based analysis and point-of-care approach to detect VOCs and gases for environmental monitoring and disease diagnosis. Additionally, we highlight the development of smart sensors that work on the principle of electrochemical detection and provide examples of the same through an extensive literature review. At the end of this review, we highlight various challenges and future perspectives.

Electrochemical Soil Nitrate Sensor for In Situ Real-Time Monitoring.

Sustainable agriculture is the answer to the rapid rise in food demand which is straining our soil, leading to desertification, food insecurity, and ecosystem imbalance. Sustainable agriculture revolves around having real-time soil health information to allow farmers to make the correct decisions. We present an ion-selective electrode (ISE) electrochemical soil nitrate sensor that utilizes electrochemical impedance spectroscopy (EIS) for direct real-time continuous soil nitrate measurement without any soil pretreatment. The sensor functionality, performance, and in-soil dynamics have been reported. The ion-selective electrode (ISE) is applied by drop casting onto the working electrode. The study was conducted on three different soil textures (clay, sandy loam, and loamy clay) to cover the range of the soil texture triangle. The non-linear regression models showed a nitrate-dependent response with R2 > 0.97 for the various soil textures in the nitrate range of 5-512 ppm. The validation of the sensor showed an error rate of less than 20% between the measured nitrate and reference nitrate for multiple different soil textures, including ones that were not used in the calibration of the sensor. A 7-day-long in situ soil study showed the capability of the sensor to measure soil nitrate in a temporally dynamic manner with an error rate of less than 20%.

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.

How safe is our food we eat? An electrochemical lab-on-kitchen approach towards combinatorial testing for pesticides and GMOs; A case study with edamame.

In our daily life, as consumers we are constantly made aware of the impact of pesticides and other modifications to food products derived from genetically modified organisms (GMO's) that have an impact on human health. In our connected world, there is an immense interest for on-demand information about food quality prior to consumption. The gold standard method to detect pesticides or GMOs residues in food is complex and is not amenable to rapid consumer use. In this study, we demonstrate the feasibility of an electrochemical portable sensing approach for the simultaneous direct detection of spiked pesticides chlorpyrifos (Chlp) and GMOs protein Cry1Ab in real edamame soy matrix. The immunoassay based two-plex sensing platform was fabricated using respective antibody's Chlp on one side and Cry1Ab on other side. A simple lab-on-kitchen level preparation of matrix has been demonstrated and sensor response was tested using non-faradaic electrochemical impedance spectroscopy (EIS), which showed a linear response in Cry1Ab/Chlp concentrations from 0.3 ng/mL to 243 ng/mL with limit of detection 0.3 ng /mL for both the target antigens (Cry1Ab and Chlp) respectively. The spiked and recovery test results fall within ± 20% error in real sample matrix which demonstrates the performance of the our platform with maximum residue limit (MRL) for the given targets. Such electrochemical portable multi-analyte direct sensing tool with simple matrix processing protocol can be a future commercial field-testing tool for use at everyday consumer level.

Pesticide analytical screening system (PASS): A novel electrochemical system for multiplex screening of glyphosate and chlorpyrifos in high-fat and low-fat food matrices.

On-field detection of pesticide residue in complex-food matrices is a challenge when it comes to analytical detection involving multistep extraction and purification. In this study, we test the feasibility of an electrochemical portable device for detection of spiked pesticides Glyphosate (Glyp) and Chlorpyrifos (Chlp) in low-fat and high-fat food matrix. The immunoassay based two-plex sensing platform was fabricated using respective antibody glyphosate on one side and chlorpyrifos antibody on other side. The sensor response was tested using non-faradaic electrochemical impedance spectroscopy (EIS), which showed a linear response in Glyp/Chlp concentrations from 0.3 ng/mL to 243 ng/mL with limit of detection 1 ng/mL for low fat and 1 ng/mL to 243 ng/mL with LOD 1 ng/mL for high-fat matrix respectively. The laboratory-based benchtop data was then compared with portable device for feasibility of application as portable device. Such electrochemical portable sensing approach can be a future commercial field testing tool.

A Proof-of-Concept Electrochemical Skin Sensor for Simultaneous Measurement of Glial Fibrillary Acidic Protein (GFAP) and Interleukin-6 (IL-6) for Management of Traumatic Brain Injuries.

This work demonstrates the use of a noninvasive, sweat-based dual biomarker electrochemical sensor for continuous, prognostic monitoring of a Traumatic Brain Injury (TBI) with the aim of enhancing patient outcomes and reducing the time to treatment after injury. A multiplexed SWEATSENSER was used for noninvasive continuous monitoring of glial fibrillary acidic protein (GFAP) and Interleukin-6 (IL-6) in a human sweat analog and in human sweat. Electrochemical impedance spectroscopy (EIS) and chronoamperometry (CA) were used to measure the sensor response. The assay chemistry was characterized using Fourier Transform Infrared Spectroscopy (FTIR). The SWEATSENSER was able to detect GFAP and IL-6 in sweat over a dynamic range of 3 log orders for GFAP and 2 log orders for IL-6. The limit of detection (LOD) for GFAP detection in the sweat analog was estimated to be 14 pg/mL using EIS and the LOD for IL-6 was estimated to be 10 pg/mL using EIS. An interference study was performed where the specific signal was significantly higher than the non-specific signal. Finally, the SWEATSENSER was able to distinguish between GFAP and IL-6 in simulated conditions of a TBI in human sweat. This work demonstrates the first proof-of-feasibility of a multiplexed TBI marker combined with cytokine and inflammatory marker detection in passively expressed sweat in a wearable form-factor that can be utilized toward better management of TBIs. This is the first step toward demonstrating a noninvasive enabling technology that can enable baseline tracking of an inflammatory response.

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.