Medical diagnosis is based on accurate information. For many diseases, the most valuable and specific diagnostic information is obtained from laboratory diagnostic tests to look for specific chemical or biological markers unique to the disease in question.
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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. The time to laboratory test results is crucial in providing clinicians with accurate information for treatment decisions and it has been shown that, especially for emergency medicine cases, shorter diagnostic times can impact overall length of hospital stay and improve outcomes of care.1
While offline diagnostic tests such as biopsies are likely to remain a key part of medical evaluation, particularly for the assessment of complex cytomorphology,2there has been growing interest in the use of point-of-care diagnostic devices.
Point-of-care devices can offer faster turnaround times and do not require the presence of laboratory infrastructure, making them particularly useful for rapid diagnosis of infectious diseases or non-clinical settings.3
One of the most important requirements of biosensing technologies is that they have excellent selectivity. Along with this, to diagnose many diseases where only small amounts of the chemical or biological marker may be present, the biosensing methodology must also be incredibly sensitive.
To achieve selective, rapid and sensitive detection of biomarkers, the inclusion of nanophotonic technologies in biosensors has proven to be a game changer for biosensing.4 Nanophotonic devices can be compact and provide rapid diagnostic results through the use of optical detection methods.
Nanophotonics refers to the use of light with nanoscale structures. Because nanoscale objects are comparable in size to visible light wavelengths, there may be unusual light-matter interactions that can be exploited to fabricate nanophotonic devices with particular functions. Examples of nanophotonic devices include optical waveguides, modulators, and biosensors.
For biosensing, several designs of nanophotonic devices can be used.5 Many biosensors work by selectively binding to a specific antibody or DNA aptamer, which then changes the measured optical response. Due to the small scale of the devices, phenomena such as plasmon resonances can be used to enhance signal levels and therefore improve the sensitivity of the technique.
Other types of plasmonic biosensors still use an optical response to measure with a bound or unbound substrate of interest but instead measure the binding affinity of the analyte. These types of sensors are known as affinity biosensors and can be used to detect gram-negative bacteria as well as viral disease detection, including COVID-19, for rapid point-of-care diagnosis.6
One of the main advantages of using nanophotonics and affinity-based or evanescent-field based biosensing approaches is that all of these methods are label-free. For techniques such as fluorescence microscopy to work, the biomarker must be emissive enough to be detected. As is not the case for many species, fluorescent probes are attached to the molecule as a tag which has a distinctive fluorescence upon binding.
The problem with labeling methods is that they add time to sample preparation and fluorescent labels are often specific to a certain protein or substrate. The specificity of some fluorescent tags can be useful in identifying particular structures, for example, organelles within a cell, but means that there must be an appropriate tag available to examine the disease marker of interest. Many biosensing devices based on nanophotonics circumvent this problem.
For optical-based biosensor methods, a variety of spectroscopic methods can be interfaced with the sensor. Examples may 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 compared to standard Raman measurements and, therefore, an improved detection limit.
Besides rapid and accurate diagnostics in a point-of-care device, another aspect of the attractiveness 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 scrambling to find ways to implant nanophotonic biosensors for applications such as drug concentration monitoring.
Performing continuous in situ measurements of glucose levels or concentrations of particular chemical species could aid in the management of diseases such as diabetes and a better understanding of metabolic rates and pathways of therapeutic molecules. Online and in situ monitoring would therefore be a boon for personal healthcare as well as for health research.
The main challenge for this concept of in situ nanophotonic devices to become widespread is to find 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 hence nanophotonic biosensors are already seeing widespread adoption.
References and further reading
Holland, LL, Smith, LL, & Blick, KE (2005). Reducing outliers in lab turnaround times can reduce patient length of stay in the emergency room: a study of 11 hospitals. American Journal of Clinical Pathology, 124(5), 672–674. https://doi.org/10.1309/E9QPVQ6G2FBVMJ3B
Pritzker, KPH and Nieminen, HJ (2019). Appropriateness 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 and Gerdes, J. (2008). Point-of-care diagnostics for global health. Anna. Rev. Biomed. Eng, 10, 107–144. https://doi.org/10.1146/annurev.bioeng.10.061807.160524
Anker, JN, Hall, WP, Lyandres, O., Shah, NC, Zhao, J., & Duyne, RP Van. (2008). Biosensing with plasmonic nanosensors. Natural Materials, 7, 442–453. https://doi.org/10.1038/nmat2162
Altug, H., Oh, SH, Maier, SA and Homola, J. (2022). Advances and applications of nanophotonic biosensors. Nature’s Nanotechnology, 17(1), 5–16. https://doi.org/10.1038/s41565-021-01045-5
Ruiz-Vega, G., Soler, M., & Lechuga, LM (2021). Nanophotonic biosensors for point-of-care COVID-19 diagnosis and coronavirus monitoring. JPhys Photonics, 3(1). https://doi.org/10.1088/2515-7647/abd4ee
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