The next generation lateral flow assays and the integration of nanomaterials, a review

by Virginia Greco

In an article published in ‘Chemical Reviews’, members of the ICN2 Nanobioelectronic and Biosensors Group discuss the developments carried out over the latest ten years in the field of lateral flow assay technology for diagnostics and other sensing applications. The different strategies used to overcome some of the limitations of currently used LFAs are analysed, with special focus on the contribution of nanomaterials and nanotechnologies.

Later Flow Assays (LFAs) are currently the most largely used sensors for point-of-care diagnostic, as well as for environmental and food safety monitoring. The key to their success is their simplicity, due to the use of paper-based substrates, together with rapid delivery of the test result. Cheap, easy to use, adaptable and sustainable, LFAs are great tools, but they present a few limitations that hinder their applicability and that researchers are trying to overcome. In particular, these sensors can only identify one target analyte at a time and are not suitable for quantitative measurements (they just provide a yes/no response). In addition, LFAs lack the sensitivity required for low concentration analyte detection, especially in complex biological samples.

Over the latest ten years, many developments have been pursued with the goal of improving LFA performance, as clearly shown in a review article recently published in Chemical Reviews and featured on the frontispiece of the issue. The authors, who are current and former members of the ICN2 Nanobioelectronics and Biosensors Group, led by ICREA Prof. Arben Merkoçi, provide a thorough and well organised compendium of the different approaches adopted to design enhanced LFAs, and the most relevant results obtained. Particular emphasis is given to the strategies that can synergically address the various challenges and to the relevant role played by nanomaterials and nanotechnologies in this quest.

After offering such a panoramic of the recent studies in this field, the authors discuss the factors that delay or prevent the commercial adoption of these technological advances. They identify two main issues: the lack of funding systems to support the improvement of the readiness level of a technology from the ideal conditions of the laboratory to its application in a real-life setting, and the high cost and complexity of obtaining regulatory approval (which is particularly burdensome in the case of health applications).

The paper concludes with a personal evaluation by the authors of the techniques covered, highlighting for each one both the advantages and the aspects to be improved. Among all the strategies discussed, they consider the adoption of Surface Enhanced Raman Scattering (SERS) as an alternative readout method, with respect to the classic optical one, as the most promising for near future applications. In fact, portable SERS readers able to scan the sensor paper strip and to provide a quantitative response have already been developed. It has also been proved that they are more sensitive, that can detect different analytes at once and that, in specific conditions, exhibit better performance in complex media analysis. On the other hand, though, further developments are required to make these SERS readers cheaper, faster and more user-friendly.

As the authors of this review point out, research advances are showing that the optical LFAs, which produce a calorimetric or fluorescent signal, present strong limitations and thus will be replaced by LFA sensors based on other types of signals and transduction methods –such as temperature differences, magnetic effects and Raman scattering. Dedicated software and applications will also be used more extensively, as they allow automating and speeding up the signal analysis and the interpretation of the results.

Image:

The image on the cover highlights the evolution of lateral flow biosensors in recent years, trying to bring all the recent developments and techniques into a single image. Today, it is possible to integrate several nanomaterials with multiple readout systems, obtain quantitative results with very high sensitivity, and pre-treat and separate samples in the same device. The lateral flow remains the simplest and most user-friendly biosensor ever developed.

[Credit: Dámaso Torres/ICN2]

Reference article:

Amadeo Sena-Torralba, Ruslan Álvarez-Diduk, Claudio Parolo, Andrew Piper, and Arben Merkoçi, Toward Next Generation Lateral Flow Assays: Integration of Nanomaterials. Chem. Rev. 2022, 122, 18, 14881–14910. DOI: 10.1021/acs.chemrev.1c01012