Citation: Pour, S.R.S.; Calabria, D.; Emamiamin, A.; Lazzarini, E.; Pace, A.; Guardigli, M.; Zangheri, M.; Mirasoli, M. Electrochemical vs. Optical Biosensors for Point-of-Care Applications: A Critical Review. Chemosensors 2023, 11, 546. https://doi.org/10.3390/ chemosensors11100546 Academic Editor: Alina Vasilescu Received: 20 July 2023 Revised: 20 September 2023 Accepted: 7 October 2023 Published: 21 October 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). chemosensors Review Electrochemical vs. Optical Biosensors for Point-of-Care Applications: A Critical Review Seyedeh Rojin Shariati Pour 1 , Donato Calabria 2,3 , Afsaneh Emamiamin 1 , Elisa Lazzarini 2 , Andrea Pace 2 , Massimo Guardigli 2,3,4 , Martina Zangheri 1,5,6, * and Mara Mirasoli 1,3,4, * 1 Department of Chemistry “Giacomo Ciamician”, Alma Mater Studiorum, University of Bologna, Tecnopolo di Rimini, Via Dario Campana 71, I-47922 Rimini, Italy; seyedeh.shariatipou3@unibo.it (S.R.S.P.); afsaneh.emamiamin@studio.unibo.it (A.E.) 2 Department of Chemistry “Giacomo Ciamician”, Alma Mater Studiorum, University of Bologna, Via Francesco Selmi 2, I-40126 Bologna, Italy; donato.calabria2@unibo.it (D.C.); elisa.lazzarini6@unibo.it (E.L.); andrea.pace7@unibo.it (A.P.); massimo.guardigli@unibo.it (M.G.) 3 Interdepartmental Centre for Industrial Aerospace Research (CIRI AEROSPACE), Alma Mater Studiorum, University of Bologna, Via Baldassarre Canaccini 12, I-47121 Forlì, Italy 4 Interdepartmental Centre for Industrial Research in Renewable Resources, Environment, Sea, and Energy (CIRI FRAME), Alma Mater Studiorum, University of Bologna, Via Sant’Alberto 163, I-48123 Ravenna, Italy 5 Interdepartmental Centre for Industrial Agrofood Research (CIRI AGRO), Alma Mater Studiorum, University of Bologna, Via Quinto Bucci 336, I-47521 Cesena, Italy 6 Interdepartmental Centre for Industrial Research in Advanced Mechanical Engineering Applications and Materials Technology (CIRI MAM), Alma Mater Studiorum, University of Bologna, Viale Risorgimento 2, I-40136 Bologna, Italy * Correspondence: martina.zangheri2@unibo.it (M.Z.); mara.mirasoli@unibo.it (M.M.); Tel.: +39-0512099533 (M.M.) Abstract: Analytical chemistry applied to medical and diagnostic analysis has recently focused on the development of cost-effective biosensors able to monitor the health status or to assess the level of specific biomarkers that can be indicative of several diseases. The improvement of technologies relating to the possibility of the non-invasive sampling of biological fluids, as well as sensors for the detection of analytical signals and the computational capabilities of the systems routinely employed in everyday life (e.g., smartphones, computers, etc.), makes the complete integration of self-standing analytical devices more accessible. This review aims to discuss the biosensors that have been proposed in the last five years focusing on two principal detecting approaches, optical and electrochemical, which have been employed for quantifying different kinds of target analytes reaching detection limits below the clinical sample levels required. These detection principles applied to point-of-care (POC) devices have been extensively reported in literature, and even the limited examples found on the market are based on these strategies. This work will show the latest innovations considering the integration of optical and electrochemical detection with the most commonly reported analytical platforms for POC applications such as paper-based or wearable and implantable devices. Keywords: biosensor; electrochemical detection; optical detection; point-of-care; lab-on-chip; microfluidic device; paper-based device 1. Introduction New technologies for the development of portable and self-standing devices for the rapid diagnosis of health disorders are emerging every day and they are linked to advances in different areas including chemistry, bioengineering, physics, and medicine. Indeed, the latest generation of biosensors has benefited from an interdisciplinary approach that has allowed the development of sophisticated and innovative analytical systems that could potentially improve human health, particularly in the developing world. In this context, the Chemosensors 2023, 11, 546. https://doi.org/10.3390/chemosensors11100546 https://www.mdpi.com/journal/chemosensors