All rights reserved. Lab for Single Cell Nanotechnologies (Last updated 01/08/2020)
Currently available bio-nanotechnologies for cell engineering, such as polymerase chain reaction (PCR), have provided promising sensitivity and specificity in single cell analysis. However, ending up with cell death, most of them compromise the significance in comprehensive cancer / stem cell analysis. The study of cells in engineered environments achieved by advanced nanomaterials and nanotechnologies offers unparalleled perspective in understanding of cell proliferation, differentiation, and cancer initiation, metastasis. One of the cutting-edge multidisciplinary research themes in Mechanical / Biomedical Engineering is to design and manufacture advanced MEMS device for single cell study, ranging from in vitro cell biology toward in vivo medicine. In recent years, nanotechnologies have boosted nanoscale biochips and devices for single cell transfection, analysis, manipulation and therapy, with unique performances which could not be achieved with conventional techniques. Tools we are currently using for fabricating nanoscale devices include cleanroom techniques (e.g. E-beam lithography, projection photolithography, DRIE, CVD, PVD) and Polymer nanotechnology (e.g. soft lithography, hot embossing, injection molding). In collaboration with experts in other fields, we are also exploring applying advanced biomaterials (e.g. biodegradable Zn), flexible healthcare devices, and 3D printing for micro-/nanoscale biomedical devices for cellular biology.
1. 3D Nano-electroporation technology We designed a novel nano-electroporation (NEP) for high-throughput and precisely delivery of gene / drugs into living cells at single-cell resolution. With large number of cells (up to millions), we have demonstrated the unique performance of NEP techniques, including single cell dose control, uniformity, promising efficiency and cell viability (Nature Nanotechnology, 2011; Nanoscale, 2016).
2. Lab-on-Chip for cell manipulation and gene transfection Lab-on-Chip system require capture / move cells or biomolecules towards designated regions for functioning. In our research, advanced on-chip cell manipulation techniques were invented and integrated on versatile nano-electroporation platforms for precise cell manipulation and transfection. We designed 3D Magnetic Tweezers (Small, 2016), Dielectrophoresis (DEP) (Lab Chip, 2015) and Thin-film Microfluidics (Small, 2016) for cell loading, localization and sorting. We have demonstrated the unique performance of these techniques in high-through manipulating cells while massive parallel delivery of biomolecules into living cells with high uniformity, cell safety and dosage control.
3. On-chip intracellular probing We designed high-throughput intracellular probing (IP) nano-chip for DNA / mRNA interrogation in living cells. Precisely titrating the dose of probes (e.g. molecular beacons) allows us to measure the exact copies of mRNAs and DNA expression level, which can be directly read out from single cell. The extracted information facilitates to analyze cancer stem cell heterogeneity (Nano Letters, 2016), mRNA dose effects (Small, 2016), plasmids expression (Lab Chip, 2015), cell reprogramming dynamics (Nanoscale, 2016) and gene editing.
4. Implantable Patchable Nanotransfection devices for in vivo gene manipulation we directly transfected the reprogramming DNAs into mouse skin cells and efficiently reprogramming skin cells into blood vessel endothelium, which boost the blood flow in wound region in deeper layer. The device shows direct new outlook of skin reprogramming and wound healing by simple touch (Nature Nanotechnology, 2017). We currently develop flexible transfection nano-devices which can easily and friendly patch on- body / - organ for local gene transfection. The ultimate goal of this nanotechnology is to commercialize a healthcare nanotechnology for efficient and precise regenerative medicine, cancer detection and gene editing by simple patient-touch, different from any previously adopted methods.