The Nanoscopic Multimodality BioImaging Laboratory and The Micro/Nanofluidics Lab in USC pursuit research in nanoscopic and multimodality imaging of live cells, measurement and fabrication, and integration of the imaging technology with microfluidics for lab-on-a-chip applications.
Understanding subcellular structures, their functions and interaction between cells and their microenvironment is extremely important in biology, but our knowledge is limited. One of the reasons is that current optical microscopy, which has become an important tool in biological research, has limited resolution. In fact, all conventional optics-based measurements and imaging methods suffer from the diffraction limit in physics, and the spatial resolution is limited to roughly half wavelength of the light. Thus, conventional microscopes don’t have sufficiently spatial resolution to study structures and dynamic processes in biology. Furthermore, each type of microscope has limited function and performance. Visible light has limited penetration depth to image tissue and cell microenvironment. Each imaging technique has its own advantage and multimodality imaging allows acquisition of co-registered complementary data from samples and can provide more correlated data. Therefore, this project focuses on the development of (1) super resolution STED nanoscopy to bypass the diffraction limit to achieve high resolution, (2) multimodality bioimaging platform. STED nanoscopy has been an emerging breakthrough technology to overcome the diffraction limit to achieve nanoscale spatial resolution and won Nobel Prize in 2014. Multiphoton microscope can penetrate deep into tissues. Fluorescence lifetime imaging microscope (FLIM) can measure time-resolved dynamics.
We have not only an in-house developed, continuous wave (cw) laser based super resolution system, i.e. Stimulated Emission Depletion (STED), but also an in-house developed, cutting edge, two tunable femtosecond lasers based, far field, optical multifunctional and multimodality imaging system supported by NSF/MRI and NSF/CAREER. This ultrafast nanoscopic system integrates several technologies into a large system, which currently has the following performance:
- STED Nanoscopy
- Multiphoton (MP) microscopy
- Fluorescence life time imaging microscopy (FLIM) (TCSPC / FLIM, Becker & Hickl GmbH)
- Fluorescence resonant energy transfer (FRET)
- Second harmonic generation microscope (SHGM)
- Confocal microscope
- Laser induced fluorescence photobleaching anemometer (LIFPA)
- Integrated these functionalities with Lab-on-a-Chip for live cell imaging
The system consisted of a Coherent’s Chameleon Ultra II 80MHz (RoHS) Ti:Sapphire tunable femtosecond laser and Mira OPO – Fan Poled Ring Configuration optical parametric oscillator (OPO), a laser Scanning Confocal Microscope System, and PI’s PInano XYZ P-545.3C7 Piezo Stage with Capacitive Sensors with USB controller, TCSPC / FLIM, Becker & Hickl Inc, Ultra-low noise single photon detection module, etc. The system is for conventional bioimaging and bioimaging of live cells, flow velocity, concentration and temperature measurement, and nanofabrication.