Abstract

The demand for point-of-need (PON) diagnostics for clinical and other applications is continuing to grow. Much of this demand is currently serviced by biosensors, which combine a bioanalytical sensing element with a transducing device that reports results to the user. Ideally, such devices are easy to use and do not require special skills of the end user. Application-dependent, PON devices may need to be capable of measuring low levels of analytes very rapidly, and it is often helpful if they are also portable. To date, only two transduction modalities, colorimetric lateral flow immunoassays (LFIs) and electrochemical assays, fully meet these requirements and have been widely adopted at the point-of-need. These modalities are either non-quantitative (LFIs) or highly analyte-specific (electrochemical glucose meters), therefore requiring considerable modification if they are to be co-opted for measuring other biomarkers. Förster Resonance Energy Transfer (RET)-based biosensors incorporate a quantitative and highly versatile transduction modality that has been extensively used in biomedical research laboratories. RET-biosensors have not yet been applied at the point-of-need despite its advantages over other established techniques. In this review, we explore and discuss recent developments in the translation of RET-biosensors for PON diagnoses, including their potential benefits and drawbacks.

Highlights

  • Over the last 50 years, there has been a substantial trend to developing point-of-need (PON) diagnostic testing, known as “on-the-spot” or “point-of-care”, putting rapid testing into the hands of first responders, processors and consumers

  • We explored to what extent, and under what conditions, Resonance Energy Transfer (RET) might open up new opportunities in biosensing at the point-of-need

  • Biosensors have been realized through the incorporation of RET components into biological recognition elements in such a way that the presence of an analyte affects the spatial relation between the donor and acceptor molecules (Figure 1)

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Summary

Introduction

Over the last 50 years, there has been a substantial trend to developing point-of-need (PON) diagnostic testing, known as “on-the-spot” or “point-of-care”, putting rapid testing into the hands of first responders, processors and consumers. Biosensors that combine a biological recognition element with a transduction modality for the detection of a range of analytes are ideally placed to meet the requirements for accurate and repeatable PON diagnostics without deep analytical expertise on the part of the end-user. With the aim of moving rapid tests from laboratory settings to the PON, CRISPR-based technologies are being adapted to give either an electrochemical readout [25] or to be carried out on a paper strip [10] similar to that of LFIs. In this study, we investigated whether there are opportunities for emerging transduction modalities to bring new diagnostic tests to the point-of-care. We explored to what extent, and under what conditions, RET might open up new opportunities in biosensing at the point-of-need

Förster Resonance Energy Transfer Sensing Principle
PON-Suitable RET Applications
Fluorescence Resonance Energy Transfer-Based Systems
Chemiluminescence-Resonance-Energy-Transfer-Based Systems
Bioluminescence-Resonance-Energy-Transfer-Based Systems
Fluorescence-Resonance-Energy-Transfer-Based Systems
FRET-Based Systems Using Time Resolved Measurements
Conclusions and Perspectives for RET-Based PON Systems
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