The general research interests in our lab focus on design and manufacture of innovative photonics and microfluidics devices, and the integration of them to address major biomedical challenges.
Example 1: Pulse Laser Activated Cell Sorting (PLACS)
PLACS is a high speed microfluidic fluorescence activated cell sorter. It is capable of performing high purity and high throughput fluorescence activated cell sorting at 20,000 cells/sec in a single channel on a sterile, and disposable microfluidic chip. FACS is one of the most commonly used instrument for high throughput single cell analysis in numerous biomedical fields. The current commercial FACS systems are very expensive and bulky instrument that require well-trained technician to operate. Its aerosol based sorting mechanism also creates potential contamination issues when sorting infectious samples. Microfluidic FACS systems have been developed in the past 15 years and aimed to provide a compact and fully enclosed FACS system that can be used for in small clinics. However, the throughput of all prior microfluidic FACS systems is orders of magnitude lower than the current bench top version. Our pulse laser activated cell sorter (PLACS) overcome such limitation by utilizing ultrafast laser induced cavitation bubbles and the corresponding high speed microfluidic jets for steering cells.
Example 2: Photothermal Nanoblade for Large Cargo Delivery
Photothermal nanoblade utilizes metallic nanostructures to harvest short laser pulse energy and convert it into highly localized and shaped explosive cavitation bubbles, which rapidly puncture a lightly contacting cell membrane via high-speed fluidic flows and induced transient shear stress. Photothermal nanoblade can generate micrometer-sized membrane access ports for delivering highly concentrated, large-size cargo with high efficiency and cell viability into mammalian cells. Biologic and inanimate cargo over 3-orders of magnitude in size including DNA, RNA, quantum dots, 200 nm polystyrene beads, to 2 μm bacteria have also been delivered into multiple mammalian cell types including neuron cells and human embryonic stem cells.
Example 3: Biophotonics Laser Assisted Surgery Tool (BLAST)
To overcome the throughput limitation of photothermal nanoblade, a new platform called BLAST (Biophotonics Laser Assisted Surgery Tool), a massively parallel version of photothermal nanoblade, allows the delivery of cargo with sizes up to several microns into 100,000 cells in a minute, which is 5 orders of magnitude faster than any prior methods. Cargo are delivered into the cytosol of cells directly without undesirable endosome trapping. High efficiency, high cell viability, and nearly simultaneous delivery of diverse types of cargo, or a combination of them, into numerous cells under constant physiological conditions allow reliable measurements in a variety of biological settings that are impossible prior to this work.
Example 4: Optoelectronic Tweezers (OET)
OET: Optoelectronic tweezers (OET) is a new optical manipulation concept that uses projected optical images to grab and corral tiny particles with sizes ranging from hundreds of micrometers to tens of nanometers. As the name suggests, OET uses both light and electric bias to sculpt a potential landscape on a photosensitive substrate. Light first creates “virtual electrodes” on the photosensitive substrate. These virtual electrodes cause the electric field to concentrate locally (similar to the lightning rod effect). The resultant non-uniform electric field exerts forces on dielectric particles through an interaction with the induced dipole moments in both the particles and the surrounding media, a phenomenon known as dielectrophoresis (DEP). OET allows massively parallel optical manipulation (trap and transport) of more than 30,000 single cells in parallel. Recent advances in the Chiou’s lab have allowed OET to be integrated with microfluidics for high throughput and multistep single cell analysis.