Development of Integrative Optofluidic Laser Systems for Biological/Biochemical Application

The optofluidic laser is an emerging technology that integrates the microcavity, microfluidic channel, and gain medium in liquid. Further integration with biomaterials results in the optofluidic biolaser, which can emit laser light with the modulation from biological/biochemical conditions. Due to the coherent and nonlinear nature of laser emission, optofluidic biolasers are promising in ultra-sensitive biological/biochemical detections. However, the practical significance of biolasers is still under debate and a large gap still exists in the literature in reference to their application in clinical settings.;This thesis outlines the development of integrative, optofluidic laser systems that incorporate biological/biochemical materials with different optical microcavity configurations, showing unique laser characteristics and revealing the potential for the use of lasers in practical biological/biochemical analyses.;First, optofluidic lasers utilizing Forster resonant energy transfer (FRET) were examined. Optofluidic FRET lasers that incorporated fluorescent proteins, DNA tetrahedra, and polymer-coated aqueous quantum dots in the liquid gain were experimentally demonstrated with capillary-based optofluidic ring resonators. Experiments show that the laser mechanism can provide up to 100-fold enhancement to the FRET signal and that molecular configurations and molecular interactions can significantly tune the laser performance through FRET. Highly sensitive, laser-based detection schemes for molecular interactions and novel bio-controlled lasers are, thus, promising.;Second, optofluidic lasers with a single molecular layer of gain were obtained. Through surface functionalization, gain molecules were concentrated at the solid-liquid interface of a ring resonator to form a single molecular layer. A pure laser signal was generated free of fluorescence background. This scheme significantly lowers the analyte concentration required for laser operation and is an analog to surface-based fluorescence detection technologies, pointing to a new direction for laser-based analyses.;Finally, integrative optofluidic laser systems that included biological cells as an active component were studied. A FRET laser was investigated with fluorescent protein FRET pairs located inside living cells. For quantitative and statistical cell laser studies, an integrated microwell array platform was developed that features automated and high throughput cell lasing detection, which has been only rarely achieved in any previous cell lasing detection schemes. Using this integrative platform, heterogeneous cell lasing performance was observed among different cell subpopulations within one insect cell line, Sf9, when stained by a DNA-specific dye, SYTO9. This observation suggests the potential of using lasing performance to detect cellular conditions such as nucleus status.