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Introduction to the special issue of optical biosensors

Prior to the development of analytical devices to assist medical professionals, clinical diagnosis relied mostly on medical history and physical examination. Since many diseases could exhibit similar symptoms, doctors have always sought complementary validation, and rudimentary clinical tests date back thousands of years. For example, the color and odor of urine was utilized in diagnostics. In modern medicine, biosensors – analytical devices used for the detection of an analyte for in vitro tests – are a cornerstone of clinical practice, with the sensitivity of standard immunoassays measuring protein biomarkers at picomolar concentrations [1]. Advances in science and engineering in synergy and collaboration with medicine have been crucial for advances in developing biosensor technologies. While the performance of state-of-the-art biosensing technologies is sufficient for the diagnosis of infectious diseases when clear symptoms are present, it falls short – perhaps by a factor of many thousands – when high sensitivity is desired, for example, in cancer [2] or neurological disorders [3]. The biosensors are composed of a biological recognition element specific for the analyte, such as proteins, antibodies, nucleic acids, cell receptors, enzymes, pathogens, organelles, cells, etc., and a transducer element that converts the signal resulting from the interaction of the analyte into an observable and preferably quantifiable signal. Among various transduction mechanisms, those utilizing light interactions are referred to as optical biosensors. Optical biosensing arguably dates back thousands of years when subtle change of color of skin or urine was used in diagnostics. Modern optical biosensors have distinct properties and advantages such as high sensitivity, easy adaptation to multiplexed systems, and portable operation capability. While macroscopic optical observations can provide useful information, much of the biological interactions occur at the microscale or nanoscale. Thus, the synergy of nanotechnology with photonics, or nanophotonics, is extremely relevant for the development of next-generation biosensor technologies. Biological phenomena at the microscale and nanoscale have always been extremely intriguing. When Robert Hooke’s book of the microscopic world [4] was published about 400 years ago, it provided a first glimpse into previously unseen details. The advent of optical microscopy led to nanoscale observations in the biological world culminating in the 2014 Nobel Prize in Chemistry [5] awarded jointly to Eric Betzig, Stefan W. Hell, and William E. Moerner “for the development of super-resolved fluorescence microscopy”. In this special issue of Nanophotonics, we present a collection of articles on optical biosensors. Optics offers various modalities of biological sensing based on how light interacts with the analytes and specific transduction method. While fluorescence can provide exquisite sensitivity down to single molecules, exploitation of optical interferometry and novel optical surfaces and periodic structures can also yield phenomenal sensitivity without requiring any secondary labels. Among exciting recent technological developments in optical biomarker analysis is single-molecule counting or digital detection, an approach that provides resolution and sensitivity beyond the reach of ensemble measurements [6, 7]. Optical biosensors not only provide very high sensitivity but also offer chemical specificity based on optical `signatures. Furthermore, optical detection methods are amenable to integration and applications at the point of care (POC). The articles in this issue present advantages and challenges in optical biosensors. Zanchetta et al. review recent progress in label-free optical biosensing techniques and their competitive advantages. The article is organized on the basis of the specific analyte type. They argue that direct and real-time detection allows the development of simpler, compact, and rapid analytical methods for different kinds of targets, from proteins to DNA and viruses. In case of small-molecule targets, label-free detection methods become necessary; secondary molecular interactions required for labeling are not feasible. This comprehensive review discusses engineered substrates and optical methods for enhanced sensitivity as well as challenges of detection in complex matrices. They discuss the