AuNP@ZeNose (ZIF-based electrochemical nose) for detection of flu biomarker in breath.

A novel electrochemical sensor is reported for the detection of isoprene levels in breath using a ZIF-based electrochemical nose. This sensor incorporates a hybrid detection system using gold nanoparticles encapsulated inside the ZIF-8 moiety. Breath-based analysis is widely being used for monitoring the metabolic state of the body. It is associated with the change in the concentration of volatile organic compounds and inorganic gases released endogenously and can be tracked using breath as the sample. One such volatile organic compound, isoprene, has been correlated to the presence of influenza virus or respiratory inflammation. Analytical techniques such as powder X-ray diffraction, scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and tunneling electron microscopy were used to understand the structural features of the composite. The electrochemical nose system uses chronoamperometry as the transduction mechanism to monitor the diffusion kinetics of the target analyte across the electrode-electrolyte interface. The presented work demonstrates isoprene sensing with high sensitivity and specificity and a detection limit of 10 parts per billion in air. We successfully demonstrate the functionality of the ZIF-based electrochemical nose for point-of-care screening of isoprene levels by developing a prototype device using a commercially available development board. We foresee that the developed sensing platform can help in early screening for the presence of influenza virus and help control the infection rate.

Characterization of Room-Temperature Ionic Liquids to Study the Electrochemical Activity of Nitro Compounds.

Over the past few years, room-temperature ionic liquid (RTIL) has evolved as an important solvent-cum-electrolyte because of its high thermal stability and excellent electrochemical activity. Due to these unique properties, RTILs have been used as a solvent/electrolyte/mediator in many applications. There are many RTILs, which possess good conductivity as well as an optimal electrochemical window, thus enabling their application as a transducer for electrochemical sensors. Nitroaromatics are a class of organic compounds with significant industrial applications; however, due to their excess use, detection is a major concern. The electrochemical performance of a glassy carbon electrode modified with three different RTILs, [EMIM][BF4], [BMIM][BF4] and [EMIM][TF2N], has been evaluated for the sensing of two different nitroaromatic analytes: 2,6-dinitrotoluene (2,6 DNT) and ethylnitrobenzene (ENB). Three RTILs have been chosen such that they have either a common anion or cation amongst them. The sensory response has been measured using square wave voltammetry (SQWV). We found the transducing ability of [EMIM][BF4] to be superior compared to the other two RTILs. A low limit of detection (LOD) of 1 ppm has been achieved with a 95% confidence interval for both the analytes. The efficacy of varying the cationic and anionic species of RTIL to obtain a perfect combination has been thoroughly investigated in this work, which shows a novel selection process of RTILs for specific applications. Moreover, the results obtained from testing with a glassy carbon electrode (GCE) have been replicated using a miniaturized sensor platform that can be deployed easily for on-site sensing applications.

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.

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.

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.

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.

Engineering the ZIF-8 Pore for Electrochemical Sensor Applications-A Mini Review.

Zinc imidazole framework-8, abbreviated as ZIF-8, is a member of the metal organic framework (MOF) family. The chemical architecture of ZIF-8 consists of zinc metal duly coordinated with an organic ligand/fragment, resulting in a cagelike three-dimensional network with unique porosity. Because of such a unique architecture and physicochemical property, ZIF-8 has recently been explored in various applications such as gas storage, catalysis, electrochemical sensing, drug delivery, etc. Electrochemical sensors are currently a hot topic in scientific advances, where small, portable, Internet of Things (IoT)-enabled devices powered by electrochemical output show a newer path toward chemo and biosensor applications. The unique electrochemical property of ZIF-8 is hence explored widely for possible electrochemical sensor applications. The application and synthesis of the bare ZIF-8 have been widely reported for more than a decade. However, new scientific advancements depict tailoring the bare ZIF-8 structure to achieve smart hybrid ZIF-8 materials that show more advanced properties compared to bare ZIF-8. The framework is formed by joining inorganic (metal-containing) units with organic linkers by reticular synthesis, which results in the formation of a cross-linked crystalline network with permanent porosity. This unique porosity of ZIF-8 has recently been utilized for the encapsulation of suitable guest species to enhance the native physicochemical activity of ZIF-8. These engineered ZIF-8 materials show excellent results, especially for electrochemical sensing application. This review is intended to describe the research, including the one done by our group, where the ZIF-8 pore size is used for encapsulating nanoparticles, enzymes, and organic compounds to avail suitable sensor applications.

E.Co.Tech-electrochemical handheld breathalyzer COVID sensing technology.

Breathomics is widely emerging as a strategy for non-invasive diagnosis of respiratory inflammation. In this study, we have evaluated the metabolic signals associated with Coronavirus (SARS COV-2), mainly the release of nitric oxide in breath. We have demonstrated the utility of a breath analyzer-based sensor platform for the detection of trace amounts of this target species. The sensor surface is modified with Room Temperature Ionic Liquid (RTIL) that allows faster diffusion of the target gas and can be used for gas sensing application. A low limit of detection (LOD) of 50 parts per billion has been achieved with a 95% confidence interval for detection of nitric oxide.. This inhouse designed sensor is incorporated into a breath analyzer system that displays enhanced sensitivity, specificity, linearity, and reproducibility for NO gas monitoring. The developed sensor platform can detect target concentrations of NO ranging from 50 to 250 ppb, using 1-Ethyl-3-methylimidazolium Tetrafluoroborate ([EMIM]BF4) as RTIL and displays fast response time of 5 s, thereby allowing easy detection of the target gas species. The sensor successfully quantifies the diffusion current and charge modulations arising within the electrical double layer from the RTIL-NO interactions through DC-based chronoamperometry (CA). The subjects tested negative and positive are significantly different (p < 0.01). The prototype can potentially be used for human health monitoring and screening, especially during the pandemic due to its portability, small size, an embedded RTIL sensing element, integrability with a low-power microelectronic device, and an IoT interface.

ZENose (ZIF-Based Electrochemical Nose) Platform for Noninvasive Ammonia Detection.

Breathomics is a widely emerging tool for noninvasive disease diagnosis and focuses on the detection of various levels of volatile organic compounds and inorganic gases present in human breath. One of the rapid, easy-to-use, and noninvasive detection methods being investigated is a system that can measure exhaled breath ammonia levels and can be correlated to the functional state of protein metabolic pathways and the renal functioning system. In this work, we have demonstrated the development of an electrochemical nose system using ferrocene encapsulated into zeolitic imidazole framework, Fc@ZIF-8, which can be successfully used for the detection of ammonia levels in breath. This is the first report of an electrochemical gas sensor platform that uses a faradaic probe (that is ferrocene) encapsulated into a metal-organic framework cavity used for disease diagnosis by monitoring the levels of the target gas and can be used for breathomics applications. This work demonstrates that low levels of ammonia gas (up to 400 ppb) can be detected with high sensitivity and specificity. The morphological and structural characterization of the novel, synthesized Fc@ZIF-8 nanocomposite has been performed using powder X-ray diffraction, field emission scanning electron microscopy, Fourier transform infrared, ultraviolet-visible spectroscopy, and dynamic light scattering. Electrochemical characterization of the material has been performed using a standard glassy carbon electrode, and further application of the material has been shown using the in-house designed and reported spiral electrochemical notification coupled electrode, used for ammonia gas sensing. Cross-reactivity studies have also been performed to demonstrate sensor specificity toward the target gas. We demonstrate the first of its kind electrochemical bifunctional probe platform that can be used for sensing ammonia levels in breath, with high sensitivity and specificity, due to the hybrid material system-zinc-imidazole framework 8 (having excellent physisorption properties) and ferrocene (acting as a redox mediator). We envision that such a sensing system will allow noninvasive and early diagnosis of chronic kidney disease, thus leading to early treatment and a decrease in the mortality rate.

ZEUS (ZIF-based electrochemical ultrasensitive screening) device for isopentane analytics with focus on lung cancer diagnosis.

Breath analytics is currently being explored for the development of point-of-care devices in non-invasive disease detection. It is based on the measurement of volatile organic compounds (VOCs) and gases that are produced by the body because of the metabolic pathways. The levels of these metabolites vary due to alteration in the endogenous oxidative stress-related metabolic pathways and can be correlated to understand the underlying disease condition. The levels of exhaled hydrocarbons in human breath can be used to design a rapid, easy to use method for lung cancer detection. This work outlines the development of an electrochemical sensing platform that can be used for the non-invasive diagnosis of lung cancer by monitoring isopentane levels in breath. This electrochemical sensor platform involves the use of [BMIM]BF4@ZIF-8 for sensing the target analyte. This synthesized nanocomposite offers advantages for gas sensing applications as it possesses unique properties such as an electrochemically active Room Temperature Ionic Liquid (RTIL) and a crosslinking Metal Organic Framework (MOF) that provides increased surface area for gas absorption. This is the first report of a hydrocarbon-based sensor platform developed for lung cancer diagnosis. The developed sensor platform displays sensitivity and specificity for the detection of isopentane up to 600 parts-per-billion. We performed structural and morphological characterization of the synthesized nanocomposite using various analytical techniques such as PXRD, FESEM, FTIR, and DLS. We further analyzed the electrochemical activity of the synthesized nanocomposite using a standard glassy carbon electrode. The application of the nanocomposite for isopentane sensing was done using a commercially available carbon screen printed electrode. The results so obtained helped in strengthening our hypothesis and serve as a proof-of-concept for the development of a breathomics-enabled electrochemical strategy. We illustrated the specificity of the developed nanocomposite by cross-reactivity studies. We envision that the detection platform will allow sensitive and specific sensing of isopentane levels such that it can used for point of care applications in noninvasive and early diagnosis of lung cancer, thereby leading to its early treatment and decrease in mortality rate.

Electrochemical impedimetric biosensors, featuring the use of Room Temperature Ionic Liquids (RTILs): Special focus on non-faradaic sensing.

Over the last decade, significant advancements have been made in the field of biosensing technology. With the rising demand for personalized healthcare and health management tools, electrochemical sensors are proving to be reliable solutions; specifically, impedimetric sensors are gaining considerable attention primarily due to their ability to perform label-free sensing. The novel approach of using Room Temperature Ionic Liquids (RTILs) to improve the sensitivity and stability of these detection systems makes long-term continuous sensing feasible towards a wide range of sensing applications, predominantly biosensing. Through this review, we aim to provide an update on current scientific progress in using impedimetric biosensing combined with RTILs for the development of sensitive biosensing platforms. This review also summarizes the latest trends in the field of biosensing and provides an update on the current challenges that remain unsolved.

A gold nanoparticle-single-chain fragment variable antibody as an immunoprobe for rapid detection of morphine by dipstick.

Gold nanoparticle (AuNP)-based optical assays are of significant interest since the molecular phenomenon can be examined easily with change in the color of AuNPs. Herein, we report the development of a dipstick using a AuNP-labeled single-chain fragment variable (scFv) antibody for the detection of morphine. The scFv antibodies for morphine were developed using phage display-based antibody library. Immunoglobulin variable regions of heavy (V H)- and light (V L)-chain genes were connected via a glycine-serine linker isolated from murine immune repertoire and cloned into the expression vector pIT2. The scFv was produced in Escherichia coli HB2151, yielding a functional protein with a molecular weight of approximately 32 kDa. The morphine scFv was labeled with gold nanoparticles and used as an optical immunoprobe in a dipstick. The competitive dipstick assay characterized the ability of the scFv antibody to recognize free morphine. The detection range was 1-1000 ng mL-1 with a limit of detection (LOD) of 5 ng mL-1 under optimal conditions, and the IC50 value was 14 ng mL-1 for morphine. The developed optical dipstick kit of scFv antibody was capable of specifically binding to free morphine and its analogs in a solution in less than 5 min and could be useful for on-site screening of a real sample in blood, urine, and saliva.

Cell penetrating peptides in preclinical and clinical cancer diagnosis and therapy.

Delivery of imaging reagents and drugs to tumors is essential for cancer diagnosis and therapy. In addition to therapeutic and diagnostic functionalities, peptides have potential benefits such as biocompatibility, ease to synthesize, smaller size, by-passing off-target side effects, and achieving the beneficial effects with lower-administered dosages. A particular type of peptide known as cell penetrating peptides (CPP) have been predominantly studied during last twenty years as they are not only capable to translocate themselves across membranes but also allow carrier drugs to translocate across plasma membrane, by different mechanisms depending on the CPP. This is of great potential importance in drug delivery systems, as the ability to pass across membranes is crucial to many drug delivery systems. In spite of significant progress in design and application of CPP, more investigations are required to further improve their delivery to tumors, with reduced side-effect and enhanced therapeutic efficacy. In this review, we emphasis on current advancements in preclinical and clinical trials based on using CPP for more efficient delivery of anti-cancer drugs and imaging reagents to cancer tissues and individual cells associated with them. We discuss the evolution of the CPPs-based strategies for targeted delivery, their current status and strengths, along with summarizing the role of CPPs in targeted drug delivery. We also discuss some recently reported diagnostic applications of engineered protease-responsive substrates and activable imaging complexes. We highlight the recent clinical trial data by providing a road map for better design of the CPPs for future preclinical and clinical applications.

An immunochromatographic dipstick as an alternate for monitoring of heroin metabolites in urine samples.

Heroin use and addiction pose serious risks and side effects due to overdose. Quantification of heroin in biological samples is challenging due to rapid deacetylation of heroin to its active metabolites. In this study, we report the quantification of metabolic degradation of heroin by-products in biological urine samples. The presence of the drug was monitored after oral administration of heroin at different time intervals. Various biophysical techniques, such as high performance liquid chromatography (HPLC) and mass spectrometry (MS) were used to evaluate the presence of the drug. A competitive fluorescence based immunoassay was developed with a limit of detection (LOD) up to 0.01 ng mL-1 and the IC50 value was 0.1 ng mL-1, while the dipstick assay shows a LOD up to 5 ng mL-1. Rapid detection of narcotic drugs was carried out for biological urine samples collected at various time points. Validation of the developed dipstick was carried out for the standard as well as the spiked urine samples by fluorescence based immunoassay (FIA), using anti-morphine antibodies. A strong correlation (R = 0.94) was obtained between the developed dipstick and FIA assay for biological urine samples collected at various time points. The developed immunochromatographic dipstick is highly sensitive, field applicable and cost effective, and can serve as a first choice for the monitoring of narcotic drugs in blood, urine and saliva in drug addicts and athletes.

Chemiluminescence based immunoassay for the detection of heroin and its metabolites.

Introduction: Continuous use of opiates causes drug-related illnesses, which poses an alarming situation to develop sensitive detection platform. In this study, a highly sensitive and reliable chemiluminescence immunoassay (CI) has been developed for the detection of heroin and its major metabolites in spiked urine samples. Methods: To develop robust immunoassay, monoacetyl morphine-bovine serum albumin (MAM-BSA) conjugate was synthesized and characterized thoroughly by physicochemical techniques. The anti-MAM antibodies were developed, labeled with horseradish peroxidase (HRP) and immunoassay was developed to detect the presence of target drug in spiked urine samples. Results: A competitive CI was developed, where heroin, MAM, morphine, and codeine concentration were ranged from 0-1000 ng/ mL in spiked urine samples and limit of detection were 80, 95, 90, 75 pg/ mL. Conclusion: The developed CI is highly sensitive, specific, point of care, cost-effective and can be used as a routine technique for quantitative analysis for screening of narcotic drugs.