Designing electrochemical microfluidic multiplexed biosensors for on-site applications

Abstract

Clinical assessment based on a single biomarker is in many circumstances not sufficient for adequate diagnosis of a disease or for monitoring its therapy. Multiplexing, the measurement of multiple analytes from one sample and/or of the same target from different samples simultaneously, could enhance the accuracy of the diagnosis of diseases and their therapy success. Thus, there is a great and urgent demand for multiplexed biosensors allowing a low-cost, easy-to-use, and rapid on-site testing. In this work, we present a simple, flexible, and highly scalable strategy for implementing microfluidic multiplexed electrochemical biosensors (BiosensorX). Our technology is able to detect 4, 6, or 8 (different) analytes or samples simultaneously using a sequential design concept: multiple immobilization areas, where the assay components are adsorbed, followed by their individual electrochemical cells, where the amperometric signal readout takes place, within a single microfluidic channel. Here, first we compare vertical and horizontal designs of BiosensorX chips using a model assay. Owing to its easier handling and superior fluidic behavior, the vertical format is chosen as the final multiplexed chip design. Consequently, the feasibility of the BiosensorX for multiplexed on-site testing is successfully demonstrated by measuring meropenem antibiotics via an antibody-free β-lactam assay. The multiplexed biosensor platform introduced can be further extended for the simultaneous detection of other anti-infective agents and/or biomarkers (such as renal or inflammation biomarkers) as well as different (invasive and non-invasive) sample types, which would be a major step towards sepsis management and beyond. Graphical Abstract

Unraveling the Impact of Therapeutic Drug Monitoring via Machine Learning

“…In the clinical case being examined, for instance, updating patient data on an hourly basis, rather than daily, could significantly amplify the impact of TDM, especially within the first 72 hours. In this regard, use of biosensors can potentially provide accurate, on-site and rapid detection of the drug concentration from both blood and non-invasive bodily fluids including sweat, saliva, tear and breath, providing a chance to accelerate the response time of the TDM cycle [17][18][19][20][21][22] . Additionally, this sensor data can be utilized to build digital patient models, which can further enable model predictive control policies via simulating the patient response with individualized PK/PD parameters.…”

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“…Moreover, advances in microfabrication and microfluidic tecnologies have led to the development of integrated devices able to unify the sample collection, preparation, analysis, and postprocessing (known as “sample-in-answer-out” type of devices) or able to obtain multiplexed , and/or multiomic information in a minimally invasive manner.…”

“…Multiplexed electrochemical microfluidic biosensors have been developed for on-site measurement of multiple analytes from one sample and/or of the same analyte from different samples simultaneously, thus enhancing the accuracy of the diagnosis of diseases and their therapy success. ,, …”

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