Abstract
When measuring chemical information in biological fluids, challenges of cross-reactivity arise, especially in sensing applications where no biological recognition elements exist. An understanding of the cross-reactions involved in these complex matrices is necessary to guide the design of appropriate sensing systems. This work presents a methodology for investigating cross-reactions in complex fluids. First, a systematic screening of matrix components is demonstrated in buffer-based solutions. Second, to account for the effect of the simultaneous presence of these species in complex samples, the responses of buffer-based simulated mixtures of these species were characterized using an arrayed sensing system. We demonstrate that the sensor array, consisting of electrochemical sensors with varying input parameters, generated differential responses that provide synergistic information of sample. By mapping the sensing array response onto multidimensional heat maps, characteristic signatures were compared across sensors in the array and across different matrices. Lastly, the arrayed sensing system was applied to complex biological samples to discern and match characteristic signatures between the simulated mixtures and the complex sample responses. As an example, this methodology was applied to screen interfering species relevant to the application of schizophrenia management. Specifically, blood serum measurement of antipsychotic clozapine and antioxidant species can provide useful information regarding therapeutic efficacy and psychiatric symptoms. This work proposes an investigational tool that can guide multi-analyte sensor design, chemometric modeling and biomarker discovery.
Highlights
Blood is the conduit for transporting chemicals throughout the body
Differential pulse voltammetry (DPV) scans contain two major components that represent the signatures of an electroactive species, its oxidation potential (Ep) whose location varies according to the specific species’ energetics, and its oxidation current (Ip) which varies according to the species concentration
The peak information can be mapped onto a heat map, as shown in Fig. 2, to facilitate comparison across various samples or sensors
Summary
Blood is the conduit for transporting chemicals throughout the body. These chemical species perform diverse functions such as communication and energetics, and their activities are vital to the body’s effort to respond to threats and maintain homeostasis [1,2]. Blood tests are typically performed in a central laboratory facility using common bench-top equipment (i.e., chromatography, mass spectroscopy) [6], the need for real-time and frequent monitoring has led to the development of various point-ofcare (POC) devices [7]. Such portable sensor systems can access chemical information in blood and be employed on-site by health-care professionals (i.e., at an office or pharmacy) or at home by a patient or care-giver to provide faster test results and therapeutic interventions [8]. Glucose measurement is enabled by a lock-and-key sensor design whereby selective recognition elements (enzymes) recognize and transduce the chemical signal of glucose into an electrical signal [4,5]
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