Harnessing Small-Molecule Analyte Detection in Complex Media: Combining Molecularly Imprinted Polymers, Electrolytic Transistors, and Machine Learning.

Small-molecule analyte detection is key for improving quality of life, particularly in health monitoring through the early detection of diseases. However, detecting specific markers in complex multicomponent media using devices compatible with point-of-care (PoC) technologies is still a major challenge. Here, we introduce a novel approach that combines molecularly imprinted polymers (MIPs), electrolyte-gated transistors (EGTs) based on 2D materials, and machine learning (ML) to detect hippuric acid (HA) in artificial urine, being a critical marker for toluene intoxication, parasitic infections, and kidney and bowel inflammation. Reduced graphene oxide (rGO) was used as the sensory material and molecularly imprinted polymer (MIP) as supramolecular receptors. Employing supervised ML techniques based on symbolic regression and compressive sensing enabled us to comprehensively analyze the EGT transfer curves, eliminating the need for arbitrary signal selection and allowing a multivariate analysis during HA detection. The resulting device displayed simultaneously low operating voltages (<0.5 V), rapid response times (≤10 s), operation across a wide range of HA concentrations (from 0.05 to 200 nmol L-1), and a low limit of detection (LoD) of 39 pmol L-1. Thanks to the ML multivariate analysis, we achieved a 2.5-fold increase in the device sensitivity (1.007 µA/nmol L-1) with respect to the human data analysis (0.388 µA/nmol L-1). Our method represents a major advance in PoC technologies, by enabling the accurate determination of small-molecule markers in complex media via the combination of ML analysis, supramolecular analyte recognition, and electrolytic transistors.

Fast and flexible strategy to produce electrochemical paper-based analytical devices using a craft cutter printer to create wax barrier and screen-printed electrodes.

This paper describes a simple, low-cost, and highly flexible rapid prototyping method to construct electrochemical paper-based analytical device (ePAD) for multiplexed analyte determinations. The ePAD was composed of two electrochemical cell (EC) compartments, separated by hydrophobic barriers of wax, and screen-printed electrodes (SPEs) deposited directly over the surface of the filter paper. The ePAD was entirely constructed using an inexpensive craft cutter printer with no needed of a wax printer. The rapid prototyping method involves two steps: the deposition of the SPEs and the creation of the wax barriers. In this case, the SPEs were screen-printed on filter paper by using adhesive tape as mask by cutting the electrodes pattern with the cutter printer. Following, the wax barriers were created using stamps made of filter paper also cut with the printer and impregnated with wax. In the ePAD, each ECs containing an array of 4-working electrodes, allowing up to 4 replicates in a single measurement. Both ECs shared one counter and one reference electrodes, permitting the simultaneous multianalysis. The ePAD was successfully applied to simultaneous detection of paracetamol (PAR), caffeine (CAF), and ascorbic acid (AA) in drugs. PAR and CAF were detected in a sample using one EC and AA was detected, in a different sample, on the other EC, both with no chemical modifications in the working electrodes. Limits of detection of 0.04 mmol L-1 for PAR, 0.22 mmol L-1 for CAF, and 0.40 mmol L-1 for AA were obtained. The construction process proposed provide an easy way to implement screen-printing electrodes and wax barriers in filter paper to create electrochemical devices for fast and simultaneous multianalysis.