Correlating the Effect of Dynamic Variability in the Sensor Environment on Sensor Design

This dissertation studies the effect of biofluid dynamics on the electrochemical response of a wearable sensor for monitoring of chronic wounds. The research investigates various dynamic in vivo parameters and correlates them with experimentally measured behavior with wound monitoring as a use case. Wearable electrochemical biosensors suffer from several unaddressed challenges, like stability and sensitivity, that need to be resolved for obtaining accurate data. One of the major challenges in the use of these sensors is continuous variation in biofluid composition. Wound healing is a dynamic process with wound composition changing continuously. This dissertation investigates the effects of several in vivo biochemical and environmental parameters on the sensor response to establish actionable correlations. Real-time assessment of wound healing was carried out through longitudinal monitoring of uric acid and other wound fluid characteristics. A textile sensor was designed using a simple fabrication approach combining conductive inks with a polymeric substrate, for conformal contact with the wound bed. A −1 cm−2, establishing the applicability of the sensor for measurements in the physiologically relevant range. The sensor was also found to be stable for a period of 3 days when subjected to physiological and elevated temperatures (37oC and 40oC) confirming its relevance for long-term monitoring. A direct correlation between sensor response and the dynamic parameters was seen, with the results showing a ~20% deviation from the accurate UA reading. The results confirmed that as a consequence of these parameters temporally changing in the wound environment, the sensor response will be altered. The work develops mathematical models correlating this effect on sensor response to allow for real-time sensor calibration. The clinical validation studies established the feasibility of UA measurement by the developed electrochemical sensor and derive correlations between the wound chronicity and UA levels. The protocols developed in this work for the design, fabrication, and calibration of the sensor to correct for the dynamic in vivo behavior can be extended to any wearable sensor for improved accuracy

Interference of anti-nuclear antibodies on determination of anti-neutrophil cytoplasmic antibodies in patients suspected of vasculitis: a case series

Anti-neutrophil cytoplasmic antibodies (ANCA) are mainly associated with medium and small vessel vasculitis. Two main methodologies currently available for detection of these antibodies are indirect immunofluorescence (IIF) and monospecific proteinase 3 (PR3) and myeloperoxidase (MPO) based immunoassays. However, well-defined guidelines regarding mode of testing for ANCA in laboratories still don’t exist, leading to problems in diagnosis and further patient management. Anti-neutrophil cytoplasmic antibodies testing by IIF and enzyme linked immunosorbent assay (ELISA) often pose a significant challenge in diseases other than vasculitis and in overlapping autoimmune conditions. Anti-neutrophil cytoplasmic antibodies reporting by IIF can be challenging in certain circumstances. This case series aims to discuss four cases with probable interference of anti-nuclear antibodies (ANA) during ANCA testing by IIF resulting in ANCA false positivity. All four cases on subsequent reflex testing by line immunoassay (LIA) for PR3, MPO and glomerular basement membrane (GBM) antigens proved otherwise. While analysing for the presence of ANCA by IIF, the possible interference of ANA leading to a false positive ANCA result should be kept in mind and alternative methods of testing like ELISA, extended granulocyte based IIF assays with MPO and PR3 coated beads, etc., should also be advised. Probability of atypical ANCA in diseases other than vasculitis should also be considered in case of ambiguous results

Nanocomposite Bienzymatic Sensor for Monitoring Xanthine in Wound Diagnostics

This work reports a biosensor for monitoring xanthine for potential wound healing assessment. Active substrate of the biosensor has xanthine oxidase (XO) and horseradish peroxidase (HRP) physisorbed on a nanocomposite of multiwalled carbon nanotubes (MWCNT) decorated with gold nanoparticles (AuNP). The presence of HRP provided a two-fold increase in response to xanthine, and a three-fold increase in response to the nanocomposite. With a sensitivity of 155.71 nA μM−1 cm−2 the biosensor offers a detection limit of 1.3 μM, with linear response between 22 μM and 0.4 mM. Clinical sample analyses showed the feasibility of xanthine detection from biofluids in a lesion site due to diffusion of the analyte into surrounding biofluids. Higher concentrations by three-fold were observed from wound proximity, than away from injury, with an average recovery of 110%. Results show the feasibility of monitoring wound severity through longitudinal measurements of xanthine from injured vicinity

Non-invasive estimation of hemoglobin, bilirubin and oxygen saturation of neonates simultaneously using whole optical spectrum analysis at point of care

The study was aimed to evaluate the performance of a newly developed spectroscopy-based non-invasive and noncontact device (SAMIRA) for the simultaneous measurement of hemoglobin, bilirubin and oxygen saturation as an alternative to the invasive biochemical method of blood sampling. The accuracy of the device was assessed in 4318 neonates having incidences of either anemia, jaundice, or hypoxia. Transcutaneous bilirubin, hemoglobin and blood saturation values were obtained by the newly developed instrument which was corroborated with the biochemical blood tests by expert clinicians. The instrument is trained using Artificial Neural Network Analysis to increase the acceptability of the data. The artificial intelligence incorporated within the instrument determines the disease condition of the neonate. The Pearson's correlation coefficient, r was found to be 0.987 for hemoglobin estimation and 0.988 for bilirubin and blood gas saturation respectively. The bias and the limits of agreement for the measurement of all the three parameters were within the clinically acceptance limit