Democratization of Point-of-Care Viral Biosensors: Bridging the Gap from Academia to the Clinic

Abstract

The COVID-19 pandemic and recent viral outbreaks have highlighted the need for viral diagnostics that balance accuracy with accessibility. While traditional laboratory methods remain essential, point-of-care solutions are critical for decentralized testing at the population level. However, a gap persists between academic proof-of-concept studies and clinically viable tools, with novel technologies remaining inaccessible to clinics due to cost, complexity, training, and logistical constraints. Recent advances in surface functionalization, assay simplification, multiplexing, and performance in complex media have improved the feasibility of both optical and non-optical sensing techniques. These innovations, coupled with scalable manufacturing methods such as 3D printing and streamlined hardware production, pave the way for practical deployment in real-world settings. Additionally, software-assisted data interpretation, through simplified readouts, smartphone integration, and machine learning, enables the broader use of diagnostics once limited to experts. This review explores improvements in viral diagnostic approaches, including colorimetric, optical, and electrochemical assays, showcasing their potential for democratization efforts targeting the clinic. We also examine trends such as open-source hardware, modular assay design, and standardized reporting, which collectively reduce barriers to clinical adoption and the public dissemination of information. By analyzing these interdisciplinary advances, we demonstrate how emerging technologies can mature into accessible, low-cost diagnostic tools for widespread testing.

Keywords: accessible diagnostics; biosensors; democratization; point-of-care (POC) testing.

Figure 1

Capture Motif-Functionalized Biosensor Surfaces. Sensing surfaces are functionalized across the various viral diagnostic approaches with motifs for capturing proteins and whole virions. (A) Proteins can be surface-tethered capture moieties, with virus-binding proteins and antibodies providing specific binding (PDB IDs 4V7Q, 1R42, 1IGT). (B) Surface-linked nucleic acids can serve a similar viral capture function while providing additional stability and cost reduction. Their programmability enables multiplexed detection for sensing multiple analytes on one sensor surface (PDB IDs 5IRE, 1CD3, 3KZ4). (C) Molecularly imprinted polymers (MIPS) can be pre-produced to capture viruses with cavities imprinted to capture specific viral proteins (PDB ID 6VXX). Structures were rendered using UCSF ChimeraX 1.9 [39], and figures were generated using Adobe Illustrator version 24.

Figure 2

Schematics of Viral Biosensing Approaches. Viral biosensing can be achieved in a variety of ways. (A) Label-free biosensing methods can track the association of surface-immobilized capture motifs and analytes in real time, giving rise to kinetic and binding affinity parameters. (B) Colorimetric assays detect viral particles through the association of viral particles with reporter-conjugated capture moieties, producing a distinct visible readout with simple assay administration. Viral detection is coupled with a progressive, visible color change in the sample, while a virus-free sample remains as the same starting color. (C) Lateral flow assays are a clinical standard due to their relative simplicity and binary readout resulting from reporter-conjugated binding activity coupled with viral binding. The different antibodies, consisting of control, test, and tag-conjugated, are colored in white, green, and orange respectively to illustrate the multiple regions through which the sample flows. (D) Electrochemical assays can utilize the electrical signals associated with chemical binding events, and they can take several approaches, which include cyclic voltammetry, amperometry, and electrochemical impedance spectroscopy. (PDB IDs: 1D28, 4V7Q, 1IGT, 1R42, 6VXX). Structures were rendered in UCSF ChimeraX 1.9 [39], and figures were generated in Affinity Designer 2.

Figure 3

Aspects of POC Accessibility to Novel Diagnostics. (A) Additive manufacturing enables the increasingly affordable production of a range of physical diagnostic components, ranging from consumables like swabs and PPE to instrumental hardware like housings and microfluidic systems, as well as replacement internal components for instrumental repair. (B) Advancements in sensor surface production can lower the barrier to entry for administering viral assays either through scalable, automated manufacturing, pre-functionalization with immobilized capture motifs, or the utilization of multiple capture motifs for multiplexed sensing (PDB ID 6VXX). (C) Software assistance also lowers the barrier for data interpretation through simplified results for complex readouts, the machine learning-assisted processing of increasingly large datasets, and the incorporation of smartphones as processing devices to reduce cost. (D) Contact tracing drives outbreak monitoring and digital exposure alerts, easing the burden on clinicians and enabling the preemptive stocking of assay reagents. Additionally, accessible literature can equip both clinicians and the public with a greater understanding of viral infections and the administration of their respective assays (PDB ID 4V7Q)—structures were rendered in UCSF ChimeraX 1.9 [39] and figures were generated in Affinity Designer 2.