Medical diagnosis depends 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 specific 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 tests were performed in a hospital laboratory. Turnaround time for lab test results is critical to providing clinicians with accurate information for treatment decisions, and it has been shown that shorter diagnosis times, especially for emergency medicine, can affect overall length of hospital stay and improve care outcomes.1
While offline diagnostic tests such as biopsies likely remain an important part of medical assessment, particularly for the evaluation of complex cytomorphology,2there is a growing interest in the use of point-of-care devices for diagnostics.
Point-of-care devices can provide faster turnaround times and require no laboratory infrastructure, making them particularly useful for rapid diagnosis of infectious diseases or non-clinical environments.3
One of the main requirements of biosensing technologies is that they have excellent selectivity. In addition, the biosensing methodology must also be incredibly sensitive to diagnose many diseases where only small amounts of the chemical or biological marker may be present.
For achieving selective, rapid and sensitive detection of biomarkers, the incorporation of nanophotonics technologies into biosensors has proven to be a game-changer for biosensing.4 Nanophotonics devices can be compact and provide rapid diagnostic results using optical detection methods.
Nanophotonics refers to the use of light with nanoscale structures. Because objects on the nanometer-length scale are similar in size to the wavelengths of visible light, unusual light-matter interactions can take place that can be exploited to create nanophotonic devices with certain functions. Examples of nanophotonic devices are 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 alters the measured optical response. Due to the small scale of the devices, phenomena such as plasmonic resonances can be used to improve signal levels and thus improve the sensitivity of the technique.
Other types of plasmonic biosensors still use an optical response to measure whether or not a substrate of interest is bound, but instead measure the binding affinity of the analyte. Known as affinity biosensors, this type of sensors can be used to detect gram-negative bacteria and detect viral diseases, including COVID-19, for rapid point-of-care diagnostics.6
One of the main advantages of using nanophotonics and affinity or volatile field-based approaches for 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. Since this is not the case for many species, fluorescent probes are attached to the molecule as a tag that has a characteristic fluorescence upon binding.
The problem with labeling methods is that it adds time to sample preparation and fluorescent tags are often specific to a particular protein or substrate. The specificity of certain fluorescent tags can be useful for identifying certain structures, for example organelles in a cell, but means that an appropriate tag must be available to look at the particular disease marker. Many nanophotonics-based biosensing devices circumvent this problem.
For optically based biosensor methods, a variety of spectroscopic methods can be coupled to the sensor. Examples include infrared, Raman or polarized light, all of which have different sensitivities and degrees of selectivity. Variations of certain techniques, such as surface enhanced Raman scattering (SERS), are also very powerful for biosensing applications. They have improved sensitivity over standard Raman measurements and thus an improved limit of detection.
In addition to rapid 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 consumption. 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.
Conducting continuous in-situ measurements of glucose levels or the concentrations of certain chemical species could aid in disease management in conditions such as diabetes and better understand the metabolic rates and pathways of therapeutic molecules. Online, in-situ monitoring would therefore be a boon for both personal healthcare and health research.
The biggest challenge to widely use this concept of in-situ nanophotonic devices is to find more biocompatible materials. Most nanophotonic devices are made of 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 widely used.
Read more: Nanomaterial-based virus sensors.
References and further reading
Holland, LL, Smith, LL, & Blick, KE (2005). Reducing outliers in lab turnaround time may shorten patient emergency room stays: an 11-hospital study. American Journal of Clinical Pathology, 124(5), 672-674. https://doi.org/10.1309/E9QPVQ6G2FBVMJ3B
Pritzker, KPH and Nieminen, HJ (2019). Adequacy of needle biopsy in the age of precision medicine and value-based healthcare. Arch Pathol Lab Med, 143, 1399-1415. https://doi.org/10.5858/arpa.2018-0463-RA
Yager, P., Domingo, GJ, & Gerdes, J. (2008). Point-of-Care Diagnostics for Global Health. Ann. Rev. Biomed. Scary, 10, 107-144. https://doi.org/10.1146/annurev.bioeng.10.061807.160524
Anker, JN, Hall, W.P., Lyandres, O., Shah, N.C., Zhao, J., & Duyne, R.P. Van. (2008). Biosensing with plasmonic nanosensors. Natural Materials, 7, 442-453. https://doi.org/10.1038/nmat2162
Altug, H., Oh, SH, Maier, SA, & 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
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