Medical diagnosis relies on accurate information. For many diseases, the most valuable and specific diagnostic information is obtained from laboratory-based diagnostic tests to check for specific chemical or biological markers unique to the particular disease.
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Often the principle of biosensing is used for diagnosis, where the target molecules to be detected for diagnosis are similar to those that would be generated by the immune system as part of the immune response.
Traditionally, most medical testing was performed in a hospital laboratory. Turn around time for laboratory testing results is crucial in providing clinicians with accurate information for treatment decisions and has been shown that, in particular for emergency medicine cases, shorter diagnosis times can impact the overall length of the hospital stay as well as improve care outcomes.1
While offline diagnostic tests such as biopsies are likely to remain a key part of medical assessment, particularly for the evaluation of complex cytomorphology,2 there has been growing interest in the use of point-of-care devices for diagnostics.
Point-of-care devices can offer faster turnaround times and do not require the presence of laboratory infrastructure, making them particularly useful for rapid infectious disease diagnosis or non-clinical environments.3
One of the most important requirements of biosensing technologies is that they have excellent selectivity. Alongside this, for diagnosing many diseases where only small amounts of the chemical or biological marker may be present, the biosensing methodology must also be incredibly sensitive.
For achieving selective, rapid and sensitive detection of biomarkers, the inclusion of nanophotonics technologies into biosensors has proved a game-changer for biosensing.4 Nanophotonics devices can be compact and provide rapid diagnostic results with the use of optical sensing methods.
Nanophotonics refers to the use of light with structures on the nanoscale regime. As objects on the nanometer length scale are comparable in size to the wavelengths of visible light, there can unusual light-matter interactions that can be exploited to make nanophotonic devices with particular functions. Examples of nanophotonic devices include optical waveguides, modulators and biosensors.
For biosensing, there are several designs of nanophotonic devices that can be used.5 Many biosensors work by selectively binding a specific antibody or DNA aptamer, which then changes the measured optical response. Due to the small scale of the devices, phenomena such as plasmonic resonances can be used to enhance the signal levels and therefore improve the sensitivity of the technique.
Other types of plasmonic biosensors still use an optical response to measure with a substrate of interest is bound or not but instead measure the binding affinity of the analyte. These types of sensors are known as affinity biosensors and can be used for detecting gram negative bacteria as well as the detection of viral diseases, including COVID-19, for rapid point-of-care diagnostics.6
One of the key advantages of using nanophotonics and affinity or evanescent-field-based based approaches to biosensing is that all of these methods are label-free. For techniques such as fluorescence microscopy to work, the biomarker must be sufficiently emissive to be detected. As this is not the case for many species, fluorescent probes are attached to the molecule as a tag that has a distinctive fluorescence on binding.
The issue with labeling methods is it adds time to the sample preparation and fluorescent tags are often specific to a certain protein or substrate. The specificity of certain fluorescent tags can be useful for identifying particular structures, for example, organelles in a cell, but mean there must be a suitable tag available for looking at the disease marker of interest. Many nanophotonics-based biosensing devices circumvent this problem.
For optical-based biosensor methods, a variety of spectroscopic methods can be interfaced with the sensor. Examples might include infrared, Raman or polarized light, all of which have different sensitivities and degrees of selectivity. Variations of particular techniques, such as surface-enhanced Raman scattering (SERS), are also very powerful for biosensing applications. They have improved sensitivity over standard Raman measurements and, therefore, an improved detection limit.
As well as quick and accurate diagnostics in a point-of-care device, another aspect of the appeal of nanophotonic biosensors for future development is their small footprint and low power draw. As personalized medicine and health monitoring become increasingly important, researchers are working to find ways to implant nanophotonic biosensors for applications such as drug concentration monitoring.
Performing continual in-situ measurements of glucose levels or the concentrations of particular chemical species could help with disease management with conditions like diabetes and a better understanding of the metabolic rates and pathways of therapeutic molecules. Online, in-situ monitoring would therefore be a boon for both personal healthcare as well as health research.
The main challenge for this concept of in-situ nanophotonic devices to become widely used is finding more biocompatible materials. Most nanophotonic devices are made from heavy metals with potentially toxic side effects. However, for point-of-care devices, this is not a limitation and as a result, nanophotonic biosensors are already seeing widespread uptake.
References and Further Reading
Holland, L. L., Smith, L. L., & Blick, K. E. (2005). Reducing laboratory turnaround time outliers can reduce emergency department patient length of stay: An 11-hospital study. American Journal of Clinical Pathology, 124(5), 672–674. https://doi.org/10.1309/E9QPVQ6G2FBVMJ3B
Pritzker, K. P. H., & Nieminen, H. J. (2019). Needle Biopsy Adequacy in the Era of Precision Medicine and Value-Based Health Care. Arch Pathol Lab Med, 143, 1399–1415. https://doi.org/10.5858/arpa.2018-0463-RA
Yager, P., Domingo, G. J., & Gerdes, J. (2008). Point-of-Care Diagnostics for Global Health. Ann. Rev. Biomed. Eng, 10, 107–144. https://doi.org/10.1146/annurev.bioeng.10.061807.160524
Anker, J. N., Hall, W. P., Lyandres, O., Shah, N. C., Zhao, J., & Duyne, R. P. Van. (2008). Biosensing with plasmonic nanosensors. Nature Materials, 7, 442–453. https://doi.org/10.1038/nmat2162
Altug, H., Oh, S. H., Maier, S. A., & Homola, J. (2022). Advances and applications of nanophotonic biosensors. Nature Nanotechnology, 17(1), 5–16. https://doi.org/10.1038/s41565-021-01045-5
Ruiz-Vega, G., Soler, M., & Lechuga, L. M. (2021). Nanophotonic biosensors for point-of-care COVID-19 diagnostics and coronavirus surveillance. JPhys Photonics, 3(1). https://doi.org/10.1088/2515-7647/abd4ee