We introduce a novel, antigen-independent biolaser method to generate distinctive cellular signatures. Suspension of nucleic acid-stained cells is deposited into a Fabry-Perot cavity. The cells are excited by a pump laser at various power densities and the lasing signatures of these cells are collected. A neural network based on ResNet 34 is trained to detect and differentiate lasing patterns of CTCs from WBCs using the collected lasing signatures. This neural network structure is designed to be robust against inter-cavity discrepancies in laser cavities. We tested our system on detecting circulating pancreatic cancer cells from cell lines of T cells (Jurkat) and later spiked patient samples (filtered WBCs), from lasing cavities with uncharacterized Q factors. In both cases, we were able to differentiate the CTCs with an accuracy higher than 90%.
KEYWORDS: In vivo imaging, Nanowires, Optical coherence tomography, Luminescence, Optical tracking, Microscopy, Laser optics, Frequency modulation, Fermium, Regenerative medicine
We demonstrate that the lasing emission spectra of nanowire lasers internalized by progenitor retinal pigmented epithelial cells (RPE) can be exploited as unique “identifiers” to label each individual cell during long-time in vivo observation. Since nanowires could provide a 25 dB signal enhancement in optical coherence tomography (OCT) and green emission in fluorescence microscopy (FM), we utilized OCT and FM concurrently to track the 3D trajectories of RPE cells in rabbit retina in vivo migrating towards the laser-induced wounds. Our study confirms the feasibility of nanowire lasers as novel probes in single progenitor cell tracking, which could potentially facilitate the fundamental research in regenerative medicine.
Optofluidic bio-lasers are currently of high interest for sensitive, intra-cavity, biochemical analysis. In comparison with conventional methods such as fluorescence and colorimetric detection, lasers provide us with a method for amplifying small concentration differences in the gain medium, thus achieving high sensitivity. Our previous research has demonstrated that sandwich IL-6 ELISA performed in capillary-based optofluidic laser cavity was able to achieve ultrahigh detection sensitivity (LOD between 1-10 fg/ml) with a small sample volume (~20 μL). However, such approach has several limitations such as low repeatability and long assay time (~8 hours in total, 7 hours for laser measurements). Here, we developed a novel on-chip ELISA laser platform by directly fabricating micro-wells on dielectric mirrors for immunosorbent reactions. Polystyrene microbeads of 30 μm in diameter were placed in the wells to optically enhance the resonance cavity during laser measurement, thus significantly improving reliability, shortening assay time (~1.5 hours, 30 minutes for laser measurements) while maintaining the attractive features such as small sample volume and very high sensitivity (LOD ~0.1 pg/mL for IL-6). This work pushes the ELISA laser one step closer to solving problems in realworld biochemical analysis.
We demonstrated the ultrasound modulated droplet lasers, in which the laser intensity from whispering gallery mode (WGM) of oil droplets can be reversibly enhanced up to 20-fold when the ultrasound pressure is beyond a certain threshold. The lasing enhancement was investigated with various ultrasound frequencies and pressures. Furthermore, the ultrasound modulation of the laser output was achieved by controlling the ultrasound pressure, the duty cycle, and the frequency of ultrasound bursts. Its potential application was explored via the study on a human whole blood vessel phantom. A theoretical analysis was also conducted, showing that the laser emission enhancement results from the directional emission from a deformed cavity under ultrasound pressure. Our studies reveal the unique capabilities of ultrasound modulated droplet lasers, which could lead to the development of laser emission-based microscopy for deep tissue imaging with high spatial resolution and detection sensitivity that may overcome the long-standing drawback of traditional fluorescence imaging.
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