Diffuse reflectance spectroscopy needs to tailor the light-tissue interaction model for the geometry of probing. Single-fiber reflectance (SfR) suitable for interstitial probing and center-illumination-area-detection (CIAD) convenient for non-contact sensing are two challenging geometries. We report progresses on modeling light-tissue interactions applicable to those two geometries. These progresses have been applied to interstitial monitoring of cerebral oxygenation changes, non-contact sensing of glucose concentration in turbid medium, and depth-resolved assessing of myoglobin oxygenation in beef, etc. A new analytical path indicating the random lasing threshold as is facilitated by modeling light-tissue interaction in a scattering medium with gain will also be discussed.

We developed novel dielectric nano-interfaces for biomedical applications. For biosensing, TiO2 metasurfaces avoids the damping loss and heating problems intrinsic to plasmonic sensors. In addition to conventional spectral shift, the imaging-based and colorimetric readouts sidestep the requirements for spectrometer or hyperspectral imaging. By working in the visible spectrum, TiO2 metasurfaces point towards ultra-compact, cost-effective, and eye-perceptible solutions for point-of-care testing. For cell mechanobiology study, TiO2 nanopatterns have minimal fluorescence interference, which are compatible with super-resolution microscopy, and thereby enable mechanistic dissection of molecular-scale signaling events, in conjunction with nanoscale manipulation of important transmembrane receptors in mechanobiology studies.

A complex instrument is ordinarily used in electrochemiluminescence (ECL) biosensors to monitor the emitted light from the chemiluminescence reaction. As a result, these biosensors may not be suitable for point-of-need (PON) testing, which is critical in healthcare diagnostics. Microfluidic and luminol-based ECL systems were integrated on a CMOS chip to create a miniaturized ECL sensor for PON applications in this study. The findings demonstrated that this novel lab-on-a-chip system could detect uric acid levels as an essential biomarker for diagnosing gout disease in urine and saliva at levels lower than the physiological range. The device's repeatability, reproducibility, and selectivity were also investigated.

Integrated photonic sensors can provide large scale, flexible detection schemes. We present the development of sensitive nanoscale ultrasound sensors, compatible with Silicon-based photonic integrated circuits (PICs). The ability to measure ultrasound has many applications, ranging from biomedical imaging to non-destructive testing. These miniaturized sensors offer wideband, sensitive ultrasound detection by exploiting the photoelastic effect at the sensor interface. We will discuss challenges and opportunities in PIC integration, and our progress towards all-optical sensor arrays. These sensors enable sensitive compact ultrasound detectors for photoacoustic-based diagnostics, tissue monitoring, and compact lab-on-a-chip bio-sensing systems.

Extracellular vesicles (EVs) carry molecular cargo that includes nucleic acids, lipids, proteins, and various other biomarkers. Raman and SERS spectroscopy are label-free spectroscopy techniques based on inelastic scattering of laser light interacting with molecular vibrations. In our study, we employed Raman and SERS spectroscopy for the detection of amyloid beta protein in the molecular cargo of small EVs and bulk chemical analysis of EVs. We observed considerable variation as a reflection of the biochemical content of EVs related to the Aβ peptide incorporated in EVs extracted from the AD cell culture model. Next, we developed a new CMOS-based sensing platform for trapping, imaging, and chemical characterization of EVs via SERS (CMOS TrICC) with the experimental enhancement factor 5.0 × 104. We employed this platform for parallel trapping and sensitive biochemical analysis of the 100 nm nanospheres and EVs.