Perfused vascularized Organ-on-a-Chip: This project was initiated as a three-way collaboration (Lee, Hughes, George). My lab’s contribution is in the development of the enabling microfluidic platform that can recapitulate the physiological ranges for vasculogenesis (J73) and scale up for high throughput identical tissue platforms (J77), connect the capillary vessels to the microfluidic channels by inducing tight anastomosis (J89), a novel method to make gel loading into tissue chambers robust for robotic automation (J92), a cancer drug screening platform using perfused vascularized 3D tissue (J93), and a large-scale drug screening platform with the vascularized capillary networks (J96).
Cell Sorting: The first cell sorting technology that my lab has developed is dielectrophoresis for sorting neural stem cells (in collaboration with Lisa Flanagan). A new way to separate cells based on dielectric frequency discretization was devised (J67) and laid the foundation for the significant paper to distinguish stem progenitor lineage by the membrane dielectric properties (J81). To make sure that the DEP fields did not affect the viability of stem cells, we tested the cells with different frequencies carefully to prove the applicability of DEP for stem cell sorting (J71). Finally, a first attempt at the scale-up of DEP for neural stem cell sorting was developed for future transplantation applications (J87, J94). A second cell sorting technology utilizes acoustic streaming based on microfabricated cavities (or lateral cavity acoustic transducers – LCAT). The ability to pump and trap cells based on size has proven to be a powerful method to sort and enrich cells continuously. We have proved this concept in J86 and by combining the high throughput sorting of inertial microfluidics with LCAT (J99), we are able to trap cells to concentrations as low as 10/mL, approaching the level of circulating tumor cell levels in blood. Finally, we have been able to process whole blood and separate the blood constituents by size as well as integrate in situ immunolabeling to develop a powerful tool for liquid biopsy and various blood based assays (J100).
Droplet microfluidics for genetic analyses and bubble therapeutics: As my lab is one of the pioneers in droplet microfluidics, we continue to develop these technologies for genetic analysis and single cell analysis. This includes droplet sorting based on viscoelasticity (J74, potential sorting amplified DNA from non-amplified), gradient generation for synthesis or cell assays (J76). The ability to control droplet size allows us to develop multiplexed vesicles including bubbles for ultrasound theranostics (basis of RO1 with UNC already expired), papers published include J78, J82, J85, J88, J90.
Point-of-Care Molecular and Cell Sensing: The LCAT technology has enabled many molecular sample preparation and analysis technologies. These include DNA fragmentation (J80), molecular beacon sensing optimization (J84), quantum dot immunoassay (J91, J95).
Single cell analysis: We are starting to develop microfluidic technologies for single cell analysis and the combination of these techniques. The first publication(J98) is a collaboration between our lab and Dr. Kumar Wickramasinghe's to use AFM tips to probe single cells trapped in a microfluidic array through a thin membrane. We also are developing a single cell transfection technique. See Xuan Li and AbrahamP. Lee, "Lipoplex-Medicated Efficient Single-Cell Transfection via Droplet Microfluidics", 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2017), Savannah, Georgia, USA, October 22-26, 2017 (Journal paper soon to be submitted).
Integrated high throughput genetic analysis in picoliter droplets
Feedback control for droplet microfluidics
Automated gene analysis in microfluidic droplets
Molecular and cellular assays in artificial cells
High-Dynamic-Range Digital Microfluidics-------
Point-of-care serodiagnostic chips
Lateral acoustic cavity transducers for particle manipulation
Micro Total Analysis System for protein array bioassay
Multifunctional hybrid micro/nanoparticles for targeted therapeutics and biosensing
a. Microbubbles for ultrasound imaging contrast agents
b. Scale-up production of microfluidic hybrid particles/bubbles
c. Biomolecular sensing with long-lasting lipid microbubbles
d. Stem cell differentiation and therapeutics
e. Nanoparticles for drug delivery to the eye
f. Microfluidic cellular encapsulation in droplets for therapeutics and tissue engineering
g. Development of artificial cells for therapeutics
Label-less sorting of neural stem cells (NSCs)
a. Dielectrophoresis (DEP) microfluidic separation and sorting of NSCs
b. Impedance cytometry and control of cells in microchannels
3D Vascularized tissue for drug testing arrays
a. 3D microchannels for delivery of cells and angiogenesis factors
group makes extensive use of the UCI
Integrated Nanosystems Research Facility (INRF):
Lab Microscopes & Cameras:
TE2000 inverted fluorescent microscope
Eclipse L150 upright high resolution microscope
microscope for basic usage and alignment
speed gray-scale camera
resolution color camera
Apparatus, Pico Plus model
Generators, Amplifiers, Oscilloscope
Hood & Plasma Machine
60 and 120 degree C