Review of Integrated Optical Biosensors for Point-Of-Care Applications.

This article reviews optical biosensors and their integration with microfluidic channels. The integrated biosensors have the advantages of higher accuracy and sensitivity because they can simultaneously monitor two or more parameters. They can further incorporate many functionalities such as electrical control and signal readout monolithically in a single semiconductor chip, making them ideal candidates for point-of-care testing. In this article, we discuss the applications by specifically looking into point-of-care testing (POCT) using integrated optical sensors. The requirement and future perspective of integrated optical biosensors for POC is addressed.

Characterizations of protein-ligand reaction kinetics by transistor-microfluidic integrated sensors.

Understanding the binding affinities and kinetics of protein-ligand interactions using a label-free method is crucial for identifying therapeutic candidates in clinical diagnostics and drug development. In this work, the IGZO-TFT (thin-film transistor) biosensor integrated with a tailored microfluidic chip was developed to explore binding kinetics of protein-ligand biochemical interactions in the real-time manner. The IGZO-TFT sensor extracts the binding characteristics through sensing biomolecules by their electrical charges. Using lysozyme and tri-N-acetyl-D-glucosamine (NAG3) as an example, we established a procedure to obtain the parameters, such as the dissociation constant, Kd, and association rate constant, ka, that are critical to biochemical reactions. The correlation between the lysozyme concentration and TFT drain current signal was first constructed. Next, solutions of lysozyme and NAG3 of different mixing ratios were prepared. They were pre-mixed for various periods of reaction time before applying to the TFT sensor to extract signals of lysozyme molecules and the concentration remaining. With the knowledge of drain current changes at different reaction times, ka and Kd can be obtained. The values from our experiment are comparable to other methods, which suggests the proposed approach can be employed to explore protein-ligand interaction kinetics in the massively parallel manner if the TFT array is considered.

Evanescent Properties of Optical Diffraction from 2-Dimensional Hexagonal Photonic Crystals and Their Sensor Applications.

The sensitivity of traditional diffraction grating sensors is limited by the spatial resolution of the measurement setup. Thus, a large space is required to improve sensor performance. Here, we demonstrate a compact hexagonal photonic crystal (PhC) optical sensor with high sensitivity. PhCs are able to diffract optical beams to various angles in azimuthal space. The critical wavelength that satisfies the phase matching or becomes evanescent was used to benchmark the refractive index of a target analyte applied on a PhC sensor. Using a glucose solution as an example, our sensor demonstrated very high sensitivity and a low limit of detection. This shows that the diffraction mechanism of hexagonal photonic crystals can be used for sensors when compact size is a concern.

Cancer cell identification by bi-color ZnO and TiO2 nanowires.

Semiconductor nanocomposites provide advantages beyond the capability of typical fluorescent materials for cancer detection. In this work, nanowire-based probes with dual color channels are employed to demonstrate the capacity of cancer cell detection. Purple emitting ZnO/antibody probes are applied to detect cancer cells and meanwhile TiO2 /antibody probes with green light emission are applied to identify normal fibroblast cells. A series of quantitative analyses are conducted to verify the correlation between the concentrations of ZnO and TiO2 probes, cell numbers, and peak intensities of the PL spectra. The results provide a quantitative reference for developing nanowire-based cancel cell probes.

Optimal lighting of RGB LEDs for oral cavity detection.

In this paper the optimal lighting for oral cavity detection is proposed. The illuminants consist of several LEDs with different intensity ratios and peak wavelengths, which can enhance the color difference between normal and abnormal regions in the oral cavity. An algorithm combined with multi-spectral imaging (MSI) and color reproduction technique is applied to find the best enhancement of this difference. The colored LEDs of the optimal lighting, the Color Rendering Index (CRI) of the illuminants, and comparison with traditional illuminants are discussed. The calculations show that color enhancement ability in the oral cavity is not entirely a function of the higher CRI of some illuminants, as the narrowband illuminants (LEDs) produce an image with greater contrast than the broadband spectra and higher CRI of traditional illuminants in the reddish oral environment. Accordingly, an illuminant with specific intensity ratio of red, green, and blue LEDs is proposed, which has optimal color enhancement for oral cavity detection. Compared with the fluorescent lighting commonly in the use now, the color difference between normal and inflamed tissues can be improved from 21.5732 to 30.5532, a 42% increase, thus making medical diagnosis more efficient, so helping patients receive early treatment.

Enhanced visualization of oral cavity for early inflamed tissue detection.

We describe a color image reconstruction method that enables both direct visualization and direct digital image acquisition from one oral tissue by using various light sources and color compensating filters. In this method, the image of the oral tissue with white light emitting diodes (LEDs) with blue color compensating filter has a larger color difference between the normal and inflamed tissues. The enhanced visualization comes from the white light color mixing between the red normal tissue and bluish white light from the LEDs. With our method, we evaluate the perceived tissue reflectance in each pixel of the image and color reproduction with different illuminated spectra. Our approach to enhancement of visually perceived color difference between normal and inflamed oral tissue involves optimization of illumination and observation conditions by allowing a significant optical contrast of illuminated spectrum to reach the observer's eyes. In comparison with a conventional daylight LED flashlight, a LED with blue filter as the illuminant for oral cavity detection enhances the color difference between normal and inflamed tissues by 32%.