Lab for Single-Cell Nanoengineering (LSCN)

Lab for Single-Cell Nanoengineering (LSCN)

The Lab for Single-Cell Nanoengineering (LSCN), and the Institute of Single Cell Engineering (单细胞工程研究所), led by Dr. Lingqian Chang(常凌乾)is under Beihang University and Beijing Advanced Innovation Center for Biomedical Engineering‍, respectively. The research in our lab is mainly focused on the innovation of Biomedical Devices and Lab on Chip for cell and molecular study.

Devices for Cell: Traditional approaches for exploring genetic or molecular dynamics in cells were usually limited by the tools functioning in manipulation, delivery, sensing and read-out. Our team developed nano-platform for on-chip high throughput cell manipulation, such as, magnetic tweezers (MTs), dielectrophoresis (DEP), and open microfluidics. We also invented advanced devices enabling safe yet efficient cellular-poration and controllable gene transfection into cells, which leads to higher efficiency, cell safety and uniformity in comparison with traditional tools. Benefited from these devices, we and collaborators further extend their applications in a wide variety of fields, such as, intracellular heterogeneity detection, cell reprogramming, gene editing, cancer cell tracking among others. We recently designed a family of self-amplification nano-probes aiming for the study of gene mutations in extremely extremely low copy number. We are able to identify the cellular heterogeneities at single cell level, drug screening and study of genetic dynamics with their impact on cellular behaviors, which were challenging to be accessed by previous techniques. More recently, we reported in vivo nano-electroporation for directly transfecting gene into skin tissues for purposed clinical applications. We showed that the nanodevices for cell poration brought the field a simple yet efficient tool for on-skin cell reprogramming, gene editing using CRISPR-Cas9, and wound healing.

        Devices for Molecules: our lab is working on microfluidic-based biosensors and POCT devices for molecular detection and analysis, toward technical translations. Our research are focused on (1) high sensitive and scalable microwell array chip for POCT nucleic acid testing based on a RT-LAMP. The device has been conducted in clinical trials in West China Hospital for diagnosis of COVID-19, and showed significantly higher performance than its commercial counterparts according to rapid speed, high sensitivity and high specificity. The practical advantages of the chip include simplicity of operation and low-cost (< 0.3 USD/ chip); (2) Cell mechanical nano-sensors: which can recognize the receptors on the cell membrane and transduce cellular force into fluorescence signals. The system enables mapping both force and motility of single cell at subcellular resolution, which provides a new route for early cancer prognosis by identifying the heterogeneities of cellular forces. (3) Wearable flexible biosensors for real-time monitoring human physiological parameters, including pH, blood glucose, lactic acid, etc.

These research have contributed the fields with more than 60 peer-reviewed journal papers, including those on Nature Nanotechnology, Nano Letters, Small, Lab Chip. More than 10 US and China Patents, and three spin-out companies.

In Overall, our contribution to the field:

  1. Nanochip for Gene Transfection and Tumor Detection: We developed a novel nano-electroporation device which can actively drive extracellular molecules into the cells with dose control, single-cell uniformity, promising delivery efficiency and cell viability. The nano-chip supports comprehensive interrogation of mRNA interrogation and cell-cell communication at single cell level, while maintaining cell alive from beginning to the end. Medical researchers from US and China use the nanotechniques to manipulate DNAs, mRNA, proteins in cells with different purposes, such as gene editing, cell reprogramming, gene analysis both in vitro and in vivo.

  2. Lab on Chip for Cell Manipulation and Analysis: We developed several high-throughput cell manipulation techniques to align more than 10,000 single cells to the nanochannel array, including Magnetic Tweezers, Dielectrophoresis (DEP) and Microfluidics. We demonstrated the unique performance of these techniques in high-through manipulating cells while massive parallel delivery of probing biomolecules into living cells with high uniformity, cell safety and dosage control. With these capabilities, researchers can both study the intracellular genetic dynamics and engineer cellular microenvironments for mimicking single-cell models.

  3. Biosensor and POCT Devices for Molecular Analysis: We developed a high sensitive and scalable microwell array chip and its portable platform for POCT nucleic acid testing in fighting against COVID-19. We also designed a smart nano-chip which manipulate single cell array onself-assembled molecular beacons, which can recognize the receptors on the cell membrane. The system provides a new route for early cancer prognosis by identifying the heterogeneitiesof cellular forces.