Designing functional materials as electrode coatings to transduce high-quality information about redox molecules in biofluids is crucial for developing the next-generation medical devices. Rapidly analyzing the neurotransmitter dopamine (DA) urinary levels can enable point-of-care testing for neuroendocrine tumors. A novel sensing electrodes array modified with biopolymer chitosan and electrocatalytic carbon nanotube films that can generate crossreactive electrochemical signals from complex biofluids, such as undiluted urine, is presented. By generating cross-reactive signals, the feasibility of quantifying DA levels from unprocessed urine samples is demonstrated. The films' electrochemical activity is characterized and modeled the additive effect of the main redox interferants in urine (norepinephrine and uric acid) on the generated electrochemical signals that overlap and mask the electrochemical signature of DA. Finally, the feasibility of successfully quantifying urinary DA levels is demonstrated by investigating two calibration approaches: 1) using a synthetic solution (1.15 µm root mean squared error (RMSE) and 4.2 µm limitof-detection (LoD) values), and 2) directly using the urine samples (2.5 µm RMSE and 9.3 µm LoD values). The outcome of this work will enhance the understanding of the overlapping and masking electrochemical signatures and their interactions with functional materials, providing better analytical tools to differentiate redox molecules in highly complex biofluids.

Electrochemical sensors based on antibody-antigen recognition events are commonly used for the rapid, label-free, and sensitive detection of various analytes. However, various parameters at the bioelectronic interface, i.e., before and after the probe (such as an antibody) assembly onto the electrode, have a dominant influence on the underlying detection performance of analytes (such as an antigen). In this work, we thoroughly investigate the dependence of the bioelectronic interface characteristics on parameters that have not been investigated in depth: the antibody density on the electrode's surface and the antigen incubation time. For this important aim, we utilized the sensitive non-faradaic electrochemical impedance spectroscopy method. We showed that as the incubation time of the antigen-containing drop solution increased, a decrease was observed in both the solution resistance and the diffusional resistance with reflecting boundary elements, as well as the capacitive magnitude of a constant phase element, which decreased at a rate of 160 ± 30 kΩ/min, 800 ± 100 mΩ/min, and 520 ± 80 pF × s (α-1) /min, respectively. Using atomic force microscopy, we also showed that high antibody density led to thicker electrode coating than low antibody density, with rootmean-square roughness values of 2.2 ± 0.2 nm versus 1.28 ± 0.04 nm, respectively. Furthermore, we showed that as the antigen accumulated onto the electrode, the solution resistance increased for high antibody density and decreased for low antibody density. Finally, the antigen detection performance test yielded a better limit of detection for low antibody density than for high antibody density (0.26 μM vs 2.2 μM). Overall, we show here the importance of these two factors and how changing one parameter can drastically affect the desired outcome.

No abstract

addition, CLZ is the only antipsychotic drug currently approved for treatmentresistant schizophrenia. The FDA has recently permitted greater flexibility in deciding whether to continue or rechallenge CLZ in patients. [2] However, CLZ, although a common evidence-based treatment in the field of mental health, is underutilized. The monitoring of CLZ is burdensome and involves frequent invasive blood draws and its treatment efficacy is suboptimal due to the difficulty in titrating its dose, since over dosage results in toxicity as well as possible side effects such as weight gain, blurred vision, confusion, fever, sweating, and dizziness. [3][4][5] Since CLZ is the only antipsychotic with a defined efficacious clinical range, [6,7] analyzing CLZ blood levels in patients easily and accurately provides important information about the clinical range. For example, CLZ serum levels that are higher than 600 ng mL −1 (1.84 µmol L −1 ) have been associated with severe side effects, toxicity, seizure, and myocarditis. [8][9][10][11][12][13][14] However, psychiatrists estimate that CLZ blood levels should be higher than a 350 ng mL −1 (1.07 µmol L −1 ) threshold level to achieve effective treatment. [15,16] Therefore, clinicians have been advocating therapeutic drug monitoring (TDM) for CLZ therapy [9,17] that can be rapidly done at the point-of-care (PoC), such as at the physician's office or at home. Along the lines of the medical treatment revolution that the glucose finger-prick blood test provided for diabetes patients, in situ analysis of CLZ blood levels in microliter samples would enable rapid CLZ detection in finger-pricked blood of schizophrenia patients. Such a blood test would provide rapid assessment of CLZ treatment efficacy, which would better manage schizophrenia treatment and care.Current analytical methods for TDM of CLZ blood levels have limited capabilities to rapidly measure CLZ levels in microliter samples. [18][19][20][21][22][23][24][25][26] Liquid chromatography, followed by tandem mass spectrometry (LC-MS/MS), [23] is the gold standard and is available in commercial laboratories. A variation of the method used for venous blood has been adapted to low-volume capillary blood using dried blood spot testing. [24,25] Briefly, the sample is dehydrated on filter paper, transferred to an analytical laboratory, and rehydrated for further analysis using an LC-MS/MS. Although the LC-MS/MS method provides The antipsychotic clozapine is the most effective medication available for schizophrenia and it is the only antipsychotic with a known efficacious clinical range. However, it is dramatically underutilized due to the inability to test clozapine blood levels in finger-pricked patients' samples. This prevents obtaining immediate blood levels information, resulting in suboptimal treatment. The development of an electrochemical microsensor is presented, which enables, for the first time, clozapine detection in microliters volume whole blood. The sensor is based on a microelectrode modified with micrometer-thick biop...

In situ analysis of multiple biomarkers in the body provides better diagnosis and enables personalized health management. Since many of these biomarkers are redox-active, electrochemical sensors have shown promising analytical capabilities to measure multiple redox-active molecules. However, the analytical performance of electrochemical sensors rapidly decreases in the presence of multicomponent biofluids due to their limited ability to separate overlapping electrochemical signals generated by multiple molecules. Here we report a novel approach to use charged chitosan-modified electrodes to alter the diffusion of ascorbic acid, clozapine, L-homocysteine, and uric acid—test molecules with various molecular charges and molecular weights. Moreover, we present a complementary approach to use chemometrics to decipher the complex set of overlapping signals generated from a mixture of differentially charged redox molecules. The partial least square regression model predicted three out of four redox-active molecules with root mean square error, Pearson correlation coefficient, and R-squared values of 125 µM, 0.947, and 0.894; 51.8 µM, 0.877, and 0.753; 55.7 µM, 0.903, and 0.809, respectively. By further enhancing our understanding of the diffusion of redox-active molecules in chitosan, the in-situ separation of multiple molecules can be enabled, which will be used to establish guidelines for the effective separation of biomarkers.