A GMR enzymatic assay for quantifying nuclease and peptidase activity.

Hydrolytic enzymes play crucial roles in cellular processes, and dysregulation of their activities is implicated in various physiological and pathological conditions. These enzymes cleave substrates such as peptide bonds, phosphodiester bonds, glycosidic bonds, and other esters. Detecting aberrant hydrolase activity is vital for understanding disease mechanisms and developing targeted therapeutic interventions. This study introduces a novel approach to measuring hydrolase activity using giant magnetoresistive (GMR) spin valve sensors. These sensors change resistance in response to magnetic fields, and here, they are functionalized with specific substrates for hydrolases conjugated to magnetic nanoparticles (MNPs). When a hydrolase cleaves its substrate, the tethered magnetic nanoparticle detaches, causing a measurable shift in the sensor's resistance. This design translates hydrolase activity into a real-time, activity-dependent signal. The assay is simple, rapid, and requires no washing steps, making it ideal for point-of-care settings. Unlike fluorescent methods, it avoids issues like autofluorescence and photobleaching, broadening its applicability to diverse biofluids. Furthermore, the sensor array contains 80 individually addressable sensors, allowing for the simultaneous measurement of multiple hydrolases in a single reaction. The versatility of this method is demonstrated with substrates for nucleases, Bcu I and DNase I, and the peptidase, human neutrophil elastase. To demonstrate a clinical application, we show that neutrophil elastase in sputum from cystic fibrosis patients hydrolyze the peptide-GMR substrate, and the cleavage rate strongly correlates with a traditional fluorogenic substrate. This innovative assay addresses challenges associated with traditional enzyme measurement techniques, providing a promising tool for real-time quantification of hydrolase activities in diverse biological contexts.

Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients.

We present compelling evidence for the existence of an extended innate viperin-dependent pathway, which provides crucial evidence for an adaptive response to viral agents, such as SARS-CoV-2. We show the in vivo biosynthesis of a family of novel endogenous cytosine metabolites with potential antiviral activities. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif, indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase. Mass spectrometry additionally enabled the characterization and quantification of the most abundant serum metabolites, showing the potential diagnostic value of the compounds for viral infections. In total, we unveiled ten nucleoside (cytosine- and uracil-based) analogue structures, eight of which were previously unknown in humans allowing us to propose a new extended viperin pathway for the innate production of antiviral compounds. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ, and IL-10, suggest an association with the viperin enzyme contributing to an ancient endogenous innate immune defense mechanism against viral infection.

A dual-binding magnetic immunoassay to predict spontaneous preterm birth.

Complications posed by preterm birth (delivery before 37 weeks of pregnancy) are a leading cause of newborn morbidity and mortality. The previous discovery and validation of an algorithm that includes maternal serum protein biomarkers, sex hormone-binding globulin (SHBG), and insulin-like growth factor-binding protein 4 (IBP4), with clinical factors to predict preterm birth represents an opportunity for the development of a widely accessible point-of-care assay to guide clinical management. Toward this end, we developed SHBG and IBP4 quantification assays for maternal serum using giant magnetoresistive (GMR) sensors and a self-normalizing dual-binding magnetic immunoassay. The assays have a picomolar limit of detections (LOD) with a relatively broad dynamic range that covers the physiological level of the analytes as they change throughout gestation. Measurement of serum from pregnant donors using the GMR assays was highly concordant with those obtained using a clinical mass spectrometry (MS)-based assay for the same protein markers. The MS assay requires capitally intense equipment and highly trained operators with a few days turnaround time, whereas the GMR assays can be performed in minutes on small, inexpensive instruments with minimal personnel training and microfluidic automation. The potential for high sensitivity, accuracy, and speed of the GMR assays, along with low equipment and personnel requirements, make them good candidates for developing point-of-care tests. Rapid turnaround risk assessment for preterm birth would enable patient testing and counseling at the same clinic visit, thereby increasing the timeliness of recommended interventions.

Sample preconcentration through airjet-induced liquid phase enrichment.

Sample preparation is essential for nucleic acid assays, affecting their sensitivity and reliability. However, this process often results in a significant loss or dilution of the analyte, which becomes a bottleneck that limits downstream assay performance, particularly for assays that accept a limited input sample volume. To overcome this challenge, we present an evaporative-based sample enrichment method that uses an airjet to concentrate analytes within a small, defined volume by reversing the coffee-ring effect. A small, concentrated sample can then be collected for analysis to increase the initial sample load. The effectiveness of the reported airjet enrichment was quantified using qPCR of λ-DNA, HeLa-S3 RNA, and heat-inactivated SARS-CoV-2 samples. Comparisons between airjet enrichment and conventional evaporative concentration methods demonstrated significant advantages of airjet enrichment, including the ability to concentrate a high percentage of analyte within a 1 µL volume. The enrichment method was then integrated and adapted for various fluid volumes commonly found in nucleic acid sample preparation procedures. Here, airjet enrichment reduced the overall Cq by an average of 9.27 cycles for each analyte, resulting in a 600-fold enrichment from the initial concentration. To perform selective enrichment and prevent salt-based interference in downstream analysis, PEG was added to reduce the co-enrichment of salt. In addition, a preliminary study was conducted to explore the integration of airjet enrichment into ELISA using rabbit IgG as a model antigen. These findings demonstrate how airjet enrichment can be easily integrated into existing laboratory protocols with minimal modification and significantly improve the performance of biosensors.

Cardiometabolic disease risk markers are increased following burn injury in children.

Introduction: Burn injury in children causes prolonged systemic effects on physiology and metabolism leading to increased morbidity and mortality, yet much remains undefined regarding the metabolic trajectory towards specific health outcomes. Methods: A multi-platform strategy was implemented to evaluate the long-term immuno-metabolic consequences of burn injury combining metabolite, lipoprotein, and cytokine panels. Plasma samples from 36 children aged 4-8 years were collected 3 years after a burn injury together with 21 samples from non-injured age and sex matched controls. Three different 1H Nuclear Magnetic Resonance spectroscopic experiments were applied to capture information on plasma low molecular weight metabolites, lipoproteins, and α-1-acid glycoprotein. Results: Burn injury was characterized by underlying signatures of hyperglycaemia, hypermetabolism and inflammation, suggesting disruption of multiple pathways relating to glycolysis, tricarboxylic acid cycle, amino acid metabolism and the urea cycle. In addition, very low-density lipoprotein sub-components were significantly reduced in participants with burn injury whereas small-dense low density lipoprotein particles were significantly elevated in the burn injured patient plasma compared to uninjured controls, potentially indicative of modified cardiometabolic risk after a burn. Weighted-node Metabolite Correlation Network Analysis was restricted to the significantly differential features (q <0.05) between the children with and without burn injury and demonstrated a striking disparity in the number of statistical correlations between cytokines, lipoproteins, and small molecular metabolites in the injured groups, with increased correlations between these groups. Discussion: These findings suggest a 'metabolic memory' of burn defined by a signature of interlinked and perturbed immune and metabolic function. Burn injury is associated with a series of adverse metabolic changes that persist chronically and are independent of burn severity and this study demonstrates increased risk of cardiovascular disease in the long-term. These findings highlight a crucial need for improved longer term monitoring of cardiometabolic health in a vulnerable population of children that have undergone burn injury.

DUF2285 is a novel helix-turn-helix domain variant that orchestrates both activation and antiactivation of conjugative element transfer in proteobacteria.

Horizontal gene transfer is tightly regulated in bacteria. Often only a fraction of cells become donors even when regulation of horizontal transfer is coordinated at the cell population level by quorum sensing. Here, we reveal the widespread 'domain of unknown function' DUF2285 represents an 'extended-turn' variant of the helix-turn-helix domain that participates in both transcriptional activation and antiactivation to initiate or inhibit horizontal gene transfer. Transfer of the integrative and conjugative element ICEMlSymR7A is controlled by the DUF2285-containing transcriptional activator FseA. One side of the DUF2285 domain of FseA has a positively charged surface which is required for DNA binding, while the opposite side makes critical interdomain contacts with the N-terminal FseA DUF6499 domain. The QseM protein is an antiactivator of FseA and is composed of a DUF2285 domain with a negative surface charge. While QseM lacks the DUF6499 domain, it can bind the FseA DUF6499 domain and prevent transcriptional activation by FseA. DUF2285-domain proteins are encoded on mobile elements throughout the proteobacteria, suggesting regulation of gene transfer by DUF2285 domains is a widespread phenomenon. These findings provide a striking example of how antagonistic domain paralogues have evolved to provide robust molecular control over the initiation of horizontal gene transfer.

A non-invasive wearable stress patch for real-time cortisol monitoring using a pseudoknot-assisted aptamer.

Stress is part of everyone's life and is exacerbated by traumatic events such as pandemics, disasters, violence, lifestyle changes, and health disorders. Chronic stress has many detrimental health effects and can even be life-threatening. Long-term stress monitoring outside of a hospital is often accomplished by measuring heart rate variability. While easy to measure, this digital biomarker has low specificity, greatly limiting its utility. To address this shortcoming, we report a non-invasive, wearable biomolecular sensor to monitor cortisol levels in sweat. Cortisol is a neuroendocrine hormone that regulates homeostasis as part of the stress pathway. Cortisol is detected using an electrochemical sensor functionalized with a pseudoknot-assisted aptamer and a flexible microfluidic sweat sampling system. The skin-worn microfluidic sampler provides rapid sweat collection while separating old and new sweat. The conformation-switching aptamer provides high specificity towards cortisol while being regenerable, allowing it to monitor temporal changes continuously. The aptamer was engineered to add a pseudoknot, restricting it to only two states, thus minimizing the background signal and enabling high sensitivity. An electrochemical pH sensor allows pH-corrected amperometric measurements. Device operation was demonstrated invitro with a broad linear dynamic range (1 pM - 1 µM) covering the physiological range and a sub-picomolar (0.2 pM) limit of detection in sweat. Real-time, on-body measurements were collected from human subjects using an induced stress protocol, demonstrating in-situ signal regeneration and the ability to detect dynamic cortisol fluctuations continuously for up to 90 min. The reported device has the potential to improve prognosis and enable personalized treatments.

Biometric recognition of newborns and young children for vaccinations and health care: a non-randomized prospective clinical trial.

Although universal biometrics have been broadly called for, and there are many validated technologies to recognize adults, these technologies have been ineffective in newborns and young children. The present work describes the development and clinical testing of a fingerprint capture system for longitudinal biometric recognition of newborns and young children to support vaccination and clinical follow-up. The reader consists of a high-resolution monochromatic imaging system with an ergonomic industrial design to comfortably support and align infant fingers for imaging without a platen. This imaging approach without a platen, also called free-space imaging, reduces fingerprint distortion and ensures a more consistent finger placement. This system was tested in a newborn ward and immunization clinic at an urban hospital in Baja, California, Mexico, from 2017 to 2019. Nearly five hundred children were enrolled and followed for up to 24 months. With a protocol of imaging all ten fingers, the failure to enroll (FTE) rate was < 1% when acquiring at least two fingers for all ages and < 2% when enrolling at least four fingers. The verification (1:1) true accept rate (TAR) was 77% for newborns enrolled at ≤ 3 days of age and 96% for those enrolled at ≥ 4 days of age, both at a time gap of 15-30 days after enrollment at a false accept rate (FAR) of 0.1%. Using the top-ranked match score, the identification rate (1:many) was 86% for the ≤ 3 days enrollment age and 97% for age ≥ 4 days for a single finger at 15-30 days after enrollment. The enrollment protocol and the frequency of updating will increase for infants compared to adults. However, these data suggest that a high-resolution, free space imaging technique may fill the final gap for universal biometrics across all populations called for by the United Nations Sustainable Development Goal 16.9.

Electrochemical Carbamazepine Aptasensor for Therapeutic Drug Monitoring at the Point of Care.

Monitoring the anti-epileptic drug carbamazepine (CBZ) is crucial for proper dosing, optimizing a patient's clinical outcome, and managing their medication regimen. Due to its narrow therapeutic window and concentration-related toxicity, CBZ is prescribed and monitored in a highly personalized manner. We report an electrochemical conformation-changing aptasensor with two assay formats: a 30 min assay for routine monitoring and a 5 min assay for rapid emergency testing. To enable "sample-to-answer" testing, a de novo CBZ aptamer (K d < 12 nM) with conformational switching due to a G-quadruplex motif was labeled with methylene blue and immobilized on a gold electrode. The electrode fabrication and detection conditions were optimized using electrochemical techniques and visualized by atomic force microscopy (AFM). The aptasensor performance, including reproducibility, stability, and interference, was characterized using electrochemical impedance spectroscopy and voltammetry techniques. The aptasensor exhibited a wide dynamic range in buffer (10 nM to 100 µM) with limits of detection of 1.25 and 1.82 nM for the 5 and 30 min assays, respectively. The clinical applicability is demonstrated by detecting CBZ in finger prick blood samples (<50 µL). The proposed assays provide a promising method to enable point-of-care monitoring for timely personalized CBZ dosing.

A Scalable CMOS Molecular Electronics Chip for Single-Molecule Biosensing.

This work reports the first CMOS molecular electronics chip. It is configured as a biosensor, where the primary sensing element is a single molecule "molecular wire" consisting of a ∼100 GΩ, 25 nm long alpha-helical peptide integrated into a current monitoring circuit. The engineered peptide contains a central conjugation site for attachment of various probe molecules, such as DNA, proteins, enzymes, or antibodies, which program the biosensor to detect interactions with a specific target molecule. The current through the molecular wire under a dc applied voltage is monitored with millisecond temporal resolution. The detected signals are millisecond-scale, picoampere current pulses generated by each transient probe-target molecular interaction. Implemented in a 0.18 µm CMOS technology, 16k sensors are arrayed with a 20 µm pitch and read out at a 1 kHz frame rate. The resulting biosensor chip provides direct, real-time observation of the single-molecule interaction kinetics, unlike classical biosensors that measure ensemble averages of such events. This molecular electronics chip provides a platform for putting molecular biosensing "on-chip" to bring the power of semiconductor chips to diverse applications in biological research, diagnostics, sequencing, proteomics, drug discovery, and environmental monitoring.

Direct low field J-edited diffusional proton NMR spectroscopic measurement of COVID-19 inflammatory biomarkers in human serum.

A JEDI NMR pulse experiment incorporating relaxational, diffusional and J-modulation peak editing has been implemented for a low field (80 MHz proton resonance frequency) spectrometer system to measure quantitatively two recently discovered plasma markers of SARS-CoV-2 infection and general inflammation. JEDI spectra capture a unique signature of two biomarker signals from acetylated glycoproteins (Glyc) and the supramolecular phospholipid composite (SPC) signals that are relatively enhanced by the combination of relaxation, diffusion and J-editing properties of the JEDI experiment that strongly attenuate contributions from the other molecular species in plasma. The SPC/Glyc ratio data were essentially identical in the 600 MHz and 80 MHz spectra obtained (R2 = 0.97) and showed significantly different ratios for control (n = 28) versus SARS-CoV-2 positive patients (n = 29) (p = 5.2 × 10-8 and 3.7 × 10-8 respectively). Simplification of the sample preparation allows for data acquisition in a similar time frame to high field machines (∼4 min) and a high-throughput version with 1 min experiment time could be feasible. These data show that these newly discovered inflammatory biomarkers can be measured effectively on low field NMR instruments that do not not require housing in a complex laboratory environment, thus lowering the barrier to clinical translation of this diagnostic technology.

A 26.5 pArms Neurotransmitter Front-End With Class-AB Background Subtraction.

This paper presents an analog front-end (AFE) for fast-scan cyclic voltammetry (FSCV) with analog background subtraction using a pseudo-differential sensing scheme to cancel the large non-faradaic current before seeing the front-end. As a result, the AFE can be compact and low-power compared to conventional FSCV AFEs with dedicated digital back-ends to digitize and subtract the background from subsequent recordings. The reported AFE, fabricated in a 0.18- µ m CMOS process, consists of a class-AB common-mode rejection circuit, a low-input-impedance current conveyor, and a 1st-order current-mode delta-sigma (ΔΣ) modulator with an infinite impulse response quantizer. This AFE achieves an effective dynamic range of 83 dB with a state-of-the-art 39.2 pArms input-referred noise when loaded with a 1 nF input capacitance (26.5 pArms open-circuit) across a 5 kHz bandwidth while consuming an average power of 3.7 µW. This design was tested with carbon-fiber microelectrodes scanned at 300 V/s using flow-injection of dopamine, a key neurotransmitter.

Exploration of Human Serum Lipoprotein Supramolecular Phospholipids Using Statistical Heterospectroscopy in n-Dimensions (SHY-n): Identification of Potential Cardiovascular Risk Biomarkers Related to SARS-CoV-2 Infection.

SARS-CoV-2 infection causes a significant reduction in lipoprotein-bound serum phospholipids give rise to supramolecular phospholipid composite (SPC) signals observed in diffusion and relaxation edited 1H NMR spectra. To characterize the chemical structural components and compartmental location of SPC and to understand further its possible diagnostic properties, we applied a Statistical HeterospectroscopY in n-dimensions (SHY-n) approach. This involved statistically linking a series of orthogonal measurements made on the same samples, using independent analytical techniques and instruments, to identify the major individual phospholipid components giving rise to the SPC signals. Thus, an integrated model for SARS-CoV-2 positive and control adults is presented that relates three identified diagnostic subregions of the SPC signal envelope (SPC1, SPC2, and SPC3) generated using diffusion and relaxation edited (DIRE) NMR spectroscopy to lipoprotein and lipid measurements obtained by in vitro diagnostic NMR spectroscopy and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The SPC signals were then correlated sequentially with (a) total phospholipids in lipoprotein subfractions; (b) apolipoproteins B100, A1, and A2 in different lipoproteins and subcompartments; and (c) MS-measured total serum phosphatidylcholines present in the NMR detection range (i.e., PCs: 16.0,18.2; 18.0,18.1; 18.2,18.2; 16.0,18.1; 16.0,20.4; 18.0,18.2; 18.1,18.2), lysophosphatidylcholines (LPCs: 16.0 and 18.2), and sphingomyelin (SM 22.1). The SPC3/SPC2 ratio correlated strongly (r = 0.86) with the apolipoprotein B100/A1 ratio, a well-established marker of cardiovascular disease risk that is markedly elevated during acute SARS-CoV-2 infection. These data indicate the considerable potential of using a serum SPC measurement as a metric of cardiovascular risk based on a single NMR experiment. This is of specific interest in relation to understanding the potential for increased cardiovascular risk in COVID-19 patients and risk persistence in post-acute COVID-19 syndrome (PACS).

Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity.

For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.

J-Edited DIffusional Proton Nuclear Magnetic Resonance Spectroscopic Measurement of Glycoprotein and Supramolecular Phospholipid Biomarkers of Inflammation in Human Serum.

Proton nuclear magnetic resonance (NMR) N-acetyl signals (Glyc) from glycoproteins and supramolecular phospholipids composite peak (SPC) from phospholipid quaternary nitrogen methyls in subcompartments of lipoprotein particles) can give important systemic metabolic information, but their absolute quantification is compromised by overlap with interfering resonances from lipoprotein lipids themselves. We present a J-Edited DIffusional (JEDI) proton NMR spectroscopic approach to selectively augment signals from the inflammatory marker peaks Glyc and SPCs in blood serum NMR spectra, which enables direct integration of peaks associated with molecules found in specific compartments. We explore a range of pulse sequences that allow editing based on peak J-modulation, translational diffusion, and T2 relaxation time and validate them for untreated blood serum samples from SARS-CoV-2 infected patients (n = 116) as well as samples from healthy controls and pregnant women with physiological inflammation and hyperlipidemia (n = 631). The data show that JEDI is an improved approach to selectively investigate inflammatory signals in serum and may have widespread diagnostic applicability to disease states associated with systemic inflammation.

Point-of-care human milk testing for maternal secretor status.

We present an electrochemical impedimetric-based biosensor for monitoring the variation in human milk oligosaccharide (HMO) composition. 2'-Fucosyllactose (2'FL) is an HMO associated with infant growth, cognitive development, and protection from infectious diarrhea, one of the major causes of infant death worldwide. Due to genetic variation, the milk of some women (non-secretors) contains no or very little 2'FL with potential implications for infant health and development. However, there is currently no technology to analyze the presence and concentration of HMOs in human milk at the point-of-care (POC). The lack of such technology represents a major impediment to advancing human milk research and improving maternal-infant health. Towards this unmet need, we report an impedimetric assay for HMOs with an α-1,2 linkage, the most abundant of which is 2'FL. The sensor uses a lectin for affinity, specifically Ulex europaeus agglutinin I (UEA), with electrochemical readout. In spiked studies, the sensor exhibited a high degree of linearity (R2 = 0.991) over 0.5 to 3.0 µM with a 330-nM detection limit. The sensor performance was clinically validated using banked human milk samples and correctly identified all secretor vs. non-secretor samples. Furthermore, despite the short 35-min assay time and low sample volume (25 µL), the assay was highly correlated with HPLC measurements. This bedside human milk testing assay enables POC, "sample-to-answer" quantitative HMO measurement, and will be a valuable tool to assess milk composition.

A 174.7-dB FoM, 2nd-Order VCO-Based ExG-to-Digital Front-End Using a Multi-Phase Gated-Inverted-Ring Oscillator Quantizer.

This paper presents a second-order voltage-controlled oscillator (VCO)-based front-end for the direct digitization of biopotential signals. This work addresses the non-linearity of VCO-based ADC architectures with a mismatch resilient, multi-phase quantizer, a gated-inverted-ring oscillator (GIRO), achieving >110-dB SFDR. Leveraging the time-domain encoding of the first integrator, the ADC's power is dynamically scaled with the input amplitude enabling up to 35% power savings in the absence of motion artifacts or interference. An auxiliary input-impedance booster increases the ADC's input impedance to 50 MΩ across the entire bandwidth. Fabricated in a 65-nm CMOS process, this ADC achieves 92.3-dB SNDR in a 1 kHz BW while consuming 5.8 µW for a 174.7 dB Schreier FoM.

A 30.3 fA/√Hz Biosensing Current Front-End With 139 dB Cross-Scale Dynamic Range.

This paper presents an 8-channel array of low-noise (30.3 fA/√Hz) current sensing front-ends with on-chip microelectrode electrochemical sensors. The analog front-end (AFE) consists of a 1st-order continuous-time delta-sigma (CT ΔΣ) modulator that achieves 123 fA sensitivity over a 10 Hz bandwidth and 139 dB cross-scale dynamic range with a 2-bit programmable current reference. A digital predictor and tri-level pulse width modulated (PWM) current-steering DAC realize the equivalent performance of a multi-bit ΔΣ in an area- and power-efficient manner. The AFE consumes 50.3 µW and 0.11 mm2 per readout channel. The proposed platform was used to observe protein-ligand interactions in real-time using transient induced molecular electronic spectroscopy (TIMES), a label- and immobilization-free biosensing technique.

Cortisol Detection in Undiluted Human Serum Using a Sensitive Electrochemical Structure-Switching Aptamer over an Antifouling Nanocomposite Layer.

There is a strong and growing need to monitor stress biomarkers in vivo for real-time emotional and wellness assessment. Toward this, we report a reagent-free electrochemical aptasensor with a nanocomposite antifouling layer for sensitive and continuous detection of cortisol in human serum. A thiolated, methylene blue (MB)-tagged conformation-switching aptamer was immobilized over a gold nanowire (AuNW) nanocomposite to capture cortisol and generate a signal proportional to the cortisol concentration. The signal is recorded through differential pulse voltammetry (DPV) and chronoamperometry. The aptasensor exhibited a sensitive response with 0.51 and 0.68 nM detection limits in spiked buffer and undiluted serum samples, respectively. Interference from other structurally similar analogs, namely, epinephrine and cholic acid, was negligible (<10%). The developed nanocomposite-based aptasensor showed excellent stability in undiluted human serum, outperforming several other nanocomposite materials even after prolonged exposure. This work lays the foundation for new biosensor formats such as implantable and wearable sensors.

A Dynamically Reconfigurable ECG Analog Front-End With a 2.5× Data-Dependent Power Reduction.

This paper presents a reconfigurable electrocardiogram (ECG) analog front-end (AFE) exploiting bio-signals' inherent low activity and quasi-periodicity to reduce power consumption. This is realized by an agile, on-the-fly dynamic noise-power trade-off performed over specific cardiac cycle regions guided by a least mean squares (LMS)-based adaptive predictor leading to ∼2.5× data-dependent power savings. Implemented in 65 nm CMOS, the AFE has tunable performance exhibiting an input-referred noise ranging from 2.38 - 3.64 µVrms while consuming 307 - 769 nW from a 0.8 V supply. A comprehensive system performance verification was performed using ECG records from standard databases to establish the feasibility of the proposed predictor-based approach for power savings without compromising the system's anomaly detection capability or ability to extract pristine ECG features.