In recent years, several types of optical sensors have been probed for their aptitude in healthcare biosensing, making their applications in biomedical diagnostics a rapidly evolving subject. Optical sensors show versatility amongst different receptor types and even permit the integration of different detection mechanisms. Such conjugated sensing platforms facilitate the exploitation of their neoteric synergistic characteristics for sensor fabrication. This paper covers nearly 250 research articles since 2016 representing the emerging interest in rapid, reproducible and ultrasensitive assays in clinical analysis. Therefore, we present an elaborate review of biomedical diagnostics with the help of optical sensors working on varied principles such as surface plasmon resonance, localised surface plasmon resonance, evanescent wave fluorescence, bioluminescence and several others. These sensors are capable of investigating toxins, proteins, pathogens, disease biomarkers and whole cells in varied sensing media ranging from water to buffer to more complex environments such as serum, blood or urine. Hence, the recent trends discussed in this review hold enormous potential for the widespread use of optical sensors in early-stage disease prediction and point-of-care testing devices.

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Recent Progress in Optical Sensors for Biomedical Diagnostics.

The most polarizable localized surface plasmon resonance (LSPR) longitudinal mode of anisotropic metallic nanoparticles, such as gold bipyramids (AuBPs), is of high prominence. This optical response has tremendous applications from spectroscopy to photonics and energy devices to sensing. In conventional LSPR-based sensing, broadening and asymmetry in peaks due to chemical and instrument noise hinder obtaining a precise insight on shift positions, accordingly limiting the effectiveness and impact of LSPR sensors. Further, when investigating LSPR properties, utilizing more simplistic frequency dependent dielectric-type models can aberrantly impact the reliability of fundamental properties used for designing and fabricating efficient optical devices. For instance, more approximations can effectively limit screening intra-band and inter-band (IB) electronic transition contributions and other related optical properties. With an aim to find alternative methods to further improve their efficiency, as a first report, we devoted a particular focus on LSPR scattering inflection points (IFs) of single AuBPs. The findings reveal that tracking LSPR IFs exhibit high sensitivity over their counterpart LSPR peak shift locations. In addition, we newly detected IB transition contributions near the resonance energy in the range (1.50 eV-2.00 eV) dominated by intra-band transitions. A small increase in the local RI effectively enhances the LSPR quality factor due to IB transitions. Therefore, while neglecting IB transitions in the range below 2.4 eV can work for local air refractive index (RI), in high local RI media it can be aberrantly underestimated. Demonstrated by the use of the dielectric function based on Kramers-Kronig consistent Lorentz oscillators, our findings are in good agreement with the enhancing RI sensitivity effect. The results of this investigation support the idea that tracking curvature changes of an optical signal can be effectively used for LSPR longitudinal peak RI sensing as well as damping in the local RI environment of a single AuBP.

Homogeneous localized surface plasmon resonance inflection points for enhanced sensitivity and tracking plasmon damping in single gold bipyramids

Liposomes have been attracted attention, because liposomes can mimic the lipid bilayer membrane of cells. Scientists apply liposomes for drug delivery systems (DDSs) and for artificial cells. Hence, the handling of liposomes is very important. In particular, it is difficult to control the adsorption of the liposome onto the target selectively and the release of the drug by its own rupture. Therefore, scientists are looking for the way to carefully monitor the behavior of liposomes from adsorption to rupture in deep. We integrated quartz crystal microbalance dissipation (QCM–D) and localized surface plasmon resonance (LSPR) into a single sensor and monitored the signals from the sensor on the adsorption and rupture of liposome. The integrated sensor detected resonance frequency and dissipation from QCM-D, and wavelength shifts from LSPR simultaneously. The integrated sensor successfully monitored conformational changes of liposomes in real time upon exposure to the surfactant, Triton X-100. The data clearly revealed liposome adsorption and deformation, and disruption of membrane integrity by normalizing three signals, resonance frequency, resonance resistance and wavelength shift. In fact, we found that normalized signals were divided into 5 steps through the experiment: liposome adsorption, liposome deformation slightly, liposome conjugated with micelles of surfactant, liposome disruption and lipid bilayer covered on the surface. These results indicate that our device provides a powerful tool to gain deeper insights into biomolecular interactions, expanding numerous applications such as monitoring of conformational changes in proteins, oligonucleotides, viruses, bacteria, vesicles, and cells.

Detailed analysis of liposome adsorption and its rupture on the liquid-solid interface monitored by LSPR and QCM-D integrated sensor

A biomarker is an indicator or molecular signature that is observed in normal bodily biological processes or disease conditions. Biomarkers exist in various forms, such as proteins, peptides, antibodies, cells, metabolites, hormones, lipids, and enzymes. Developing sensitive methods for the detection of diseases at an earlier stage via these structures is essential in terms of better treatment options. Therefore, researchers have recently become interested in designing nanosensors by integrating nano-scale materials with optical, mechanical, electrical, and magnetic sensors. The use of nanostructures, such as nanotubes, nanofibers, quantum dots, and nanowires, contributes to the development of cheaper, faster, and smaller sensors, which increase sensitivity as well as enhance the detection limit and response time. This chapter examines the contributions of nanotechnology in detecting and determining biomarkers and the significance of this process in the diagnosis and treatment of diseases. Moreover, the methods of biomarker detection are analyzed via different studies as presented in the literature.

Nanosensors in Biomarker Detection

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Demonstrating a Filter-Free Wavelength Sensor with Double-Well Structure and Its Application

White-light scanning interferometry (WLSI) is often used to study the surface profiles and properties of thin films because the strength of the technique lies in its ability to provide fast and high resolution measurements. An innovative attempt is made in this paper to apply WLSI as a time-domain spectroscopic system for localized surface plasmon resonance (LSPR) sensing. A WLSI-based spectrometer is constructed with a breadboard of WLSI in combination with a spectral centroid algorithm for noise reduction and performance improvement. Experimentally, the WLSI-based spectrometer exhibits a limit of detection (LOD) of 1.2 × 10-3 refractive index units (RIU), which is better than that obtained with a conventional UV-Vis spectrometer, by resolving the LSPR peak shift. Finally, the bio-applicability of the proposed spectrometer was investigated using the rs242557 tau gene, an Alzheimer's and Parkinson's disease biomarker. The LOD was calculated as 15 pM. These results demonstrate that the proposed WLSI-based spectrometer could become a sensitive time-domain spectroscopic biosensing platform.

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An innovative application of time-domain spectroscopy on localized surface plasmon resonance sensing.

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An innovative application of time-domain spectroscopy on localized surface plasmon resonance sensing.