Integrated nanophotonics - guiding molecular analysis out from the lab

Abstract

For some years now, interest in the development of devices that allow a fast, accurate, and affordable molecular analysis of different types of samples has grown exponentially. But besides on achieving better and better analytical performance, one of the main interests of industry is on taking that technology out from the laboratory to perform the analyses directly on-site. The so-called point-of-care (POC) testing technology allows significantly reducing the response time, as the sample doesn’t need to be taken to a central laboratory, and it can be used by minimally trained personnel or even autonomously operated. These characteristics provide tremendous benefits in fields ranging from medical diagnostics to food safety, environmental monitoring, or detection of biological threats, among others. And today, in the current COVID-19 pandemic situation, the benefits of POC systems are much more evident even for the general population, which has seen how is possible being tested for SARS-CoV-2 antigens/antibodies in their local medical center, pharmacy or even at home, getting the result in few minutes. Many current POC systems are based on lateral flow immunoassays, being pregnancy tests the most popular example (until the reach of COVID-19 tests). Lateral flow tests are quite simple, easy to use, and affordable, but they only provide a yes/no response and their sensitivity might be quite limited for many applications. Another popular technology for the development of POC systems is based on electrochemical sensing, as for the case of the most important POC devices nowadays: glucometers. These devices allow to perform a quantitative detection of the target analyte (blood glucose concentration in this case) in a fast, simple, and inexpensive way, what is key for the patient to manage the disease. Many efforts are now focused on boosting the potential of POC devices to carry out a more complex and complete analysis that quickly and easily provides much more relevant information. The objective is obtaining POC devices able to perform almost any analysis, with a superior sensitivity that allows detecting very low concentrations of the target analytes in a label-free format, with minimal/none previous sample preparation, and able to simultaneously detect tens/ hundreds (or even thousands) of analytes in order to obtain a more valuable information (e.g. various disease-related biomarkers for a more reliable diagnosis or for the combined diagnosis of various diseases for the implementation of massive general screening procedures). These higher complexity analysis systems are typically referred as Lab-on-Chip (LOC) devices and they are enabled by current advances in miniaturization of the different technologies required for the creation of the cartridges used (fluidics, sensing elements, biochemistry, etc.). Among the different transduction technologies available for the development of sensing devices, optical/photonic sensors are one of those with a higher potential for LOC technology. Typically, optical sensors have been based on fluorescence or colorimetric methods, where labeling is a must. Label-free optical detection was then achieved using for example surface plasmon resonance (SPR) sensors, a technique in the frontier between optics and electronics, where very high sensitivities can be achieved, but where multiplexed detection is very limited. In this context, there is currently a huge interest in optical sensors based on guidedwave integrated nanophotonics. In this technology, photonic chips comprising different nanometric-scale elements able to guide and control light are created, being the photonic counterpart of microelectronic chips. Integrated nanophotonic sensing structures can be developed to exhibit a high interaction between the optical field and the molecules of interest, thus being able to directly detect the small variations in the refractive index caused by the presence of those substances without the need of labels. In this way, it is possible to develop sensing elements with a very high sensitivity and a size of only a few μm, so that we can integrate hundreds of them in a photonic chip of few mm for highly multiplexed detection (seeFigure 1). And very importantly, these photonic chips can be fabricated using mass-production materials, equipment, and processes coming from the microelectronics industry, thus ensuring high volumes and low costs. The first proposals of integrated nanophotonic sensors, which were based on grating couplers and on Mach-Zehnder interferometers, date back to the mid-80s and the early 90s of the last century [1,2]. Because the principle of transduction of these integrated nanophotonic sensors is based on their sensitivity to changes in the refractive index, regardless of the origin of those changes, part of the subsequent work focused on providing these photonic structures with specificity toward the analytes of interest. That was achieved by developing biofunctionalization protocols that allowed to adapt immunoassays to these photonic transduction platforms through the immobilization of specific bioreceptors. Since those early works, many other configurations of photonic sensing structures have been proposed, with interferometers, whispering