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Our research centers on development of medical devices that can benefit clinical practice.

Advanced pathogen diagnosis combating for antimicrobial resistance

Traditional pathogen diagnostics require lengthy culture-based procedures, typically 3-5 days, delaying prompt delivery of diagnostic results and treatment strategies and consequently resulting in antimicrobial resistance (Nat. Rev. Methods Primers, 2023Nat. Biomed. Eng., 2020). To response, we develop biomedical devices and methods for rapid pathogen diagnostics, which are capable of detecting cell replication (PNAS, 2019; Lab chip, 2022) and nucleic acids (Lab chip, 2021; Nanomedicine, 2019; Lab chip, 2018) of single bacterial cells. This single-cell analysis facilitates diagnosis in a timely manner, for example, a few cell cycles is sufficient to reveal replication difference of an individual bacteria and thus its antibiotic resistance. We envision to translate our devices in clinical practice.

Single-cell pathogen identification and AST by cell physical features and replication in microchannels

Single-cell AST by cell growth in a microwell

Molecular probing for single-cell pathogen identification

Digital-PCR for single-cell pathogen detection

Biosensor design for pathogen detection

References:
 

  1. Hui Li#, Kuangwen Hsieh#, Pak Kin Wong, Kathleen E Mach, Joseph C Liao, Tza-Huei Wang. Single-cell pathogen diagnostics for combating antibiotic resistance, Nature Reviews Methods Primers, 3, 6 (2023). https://doi.org/10.1038/s43586-022-00190-y. (#Co-first authors)

  2. Hui Li, Peter Torab, Kathleen E. Mach, Christine Surrette, Matthew R. England, David W. Craft, Neal J. Thomas, Joseph C. Liao, Chris Puleo, and Pak Kin Wong. Adaptable Microfluidic System for Single Cell Pathogen Classification and Antimicrobial Susceptibility Testing. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 116 (21) 10270-10279, 2019.

  3. Hui Li, Peter Torab, and Pak Kin Wong. Detection of bacterial infection via a fidget spinner, Nature Biomedical Engineering, 4, 577–578, 2020.

  4. Hui Li, Yi Lu, and Pak Kin Wong, Diffusion–reaction kinetics of microfluidic amperometric biosensors. Lab on a Chip, doi:10.1039/C8LC00794B (2018).

  5. Jian Gao#, Hui Li#, Peter Torab, Kathleen E. Mach, David W. Craft, Neal J. Thomas, Chris M. Puleo, Joseph C. Liao, Tza-Huei Wang, and Pak Kin Wong, Nanotube Assisted Microwave Electroporation for Single Cell Pathogen Identification and Antimicrobial Susceptibility Testing, Nanomedicine: Nanotechnology, Biology, and Medicine, 17, 246-253, 2019.

  6. Jiumei Hu, Liben Chen, Pengfei Zhang, Fan-En Chen, Hui Li, Kuangwen Hsieh, Sixuan Li, Johan H. Melendez, and Tza-Huei Wang. Exploiting 𝜷-Lactams-Induced Lysis and DNA Fragmentation for Rapid Molecular Antimicrobial Susceptibility Testing of Neisseria Gonorrhoeae via Dual-Digital PCR. Advanced Science, 2024, 2405272. https://doi.org/10.1002/advs.202405272 

  7. Jiumei Hu, Liben Chen, Pengfei Zhang, Kuangwen Hsieh, Hui Li, and Tza-Huei Wang, A vacuum-driven microfluidic array for multi-step sample digitalization, Lab on a Chip, doi.org/10.1039/D1LC00636C, 2021.

  8. Brian Scherer, Christine Surrette, Hui Li, Peter Torab, Erik Kvam, Craig Galligan, Steven Go, Greg Grossmann, Tyler Hammond, Tammy Johnson, Richard St-Pierre, John R. Nelson, Radislav Potyrailo, Tejas Khire, Kuangwen Hsieh, Jeff Wang, Pak Kin Wong, and Chris M. Puleo, Digital Electrical Impedance Analysis for Single Bacterium Sensing and Antimicrobial Susceptibility Testing, Lab on a Chip, doi: 10.1039/D0LC00937G (2021).

​Bioinspired ultra-repellent SLIPS technique for biomedical applications

We investigate biomedical applications of a bioinspired ultra-repellent SLIPS technique – Slippery Liquid-infused Porous Surface – a dynamic, molecularly smooth surface created by locking lubricating liquids in micro/nanostructured substrates (Sci. Adv., 2020; Nat. Sustain., 2019). It has been engineered on SLIPS-LAB, a medical system, for timely measurement of urinary stone analytes to facilitate management of high-risk stone formers. By incorporating the outperforming smoothness for minimizing friction in liquid handling, with microfluidics, precise manufacturing, and biochemistry, SLIPS-LAB enables point-of-care evaluation of urinary stone disease (Sci. Adv., 2020). Moreover, we have been working to use SLIPS for anti-fouling and anti-infection purposes.

Ultra-repellency enables SLIPS-LAB for point-of-care diagnosis of urinary stone disease and allows great potentials

Ultra-repellent LESS coating facilates anti-sticky and anti-fouling on surfaces

References:
 

  1. Hui Li, Eugene Shkolyar, Jing Wang, Alan C. Pao, Simon Conti, Joseph C. Liao, Tak Sing Wong, and Pak Kin Wong. SLIPS-LAB – A Bioinspired Bioanalysis System for Metabolic Evaluation of Urinary Stone Disease, Science Advances, 6 (21), eaba8535, 2020.

  2. Jing Wang, Lin Wang, Nan Sun, Ross Tierney, Hui Li, Margo Corsetti, Leon Williams, Pak Kin Wong, and Tak-Sing Wong, Viscoelastic solid-repellent coatings for extreme water saving and global sanitation, Nature Sustainability, 2, 1097–1105, 2019.

Microfluidic devices for drug screening

Drug screening aims to determine targets of interest among numerous potential candidates. This is typically performed using microtiter plates, which is limited for high throughput screening due to the large reagent consumptions in each assay and/or the difficulty of performing multistep biochemical assays (Trends Biotechnol., 2022). To response, we have developed microfluidic devices to address these issues, such as an automation combinatorial nanodroplet system for high throughput screening of antibiotic combinations (Lab chip, 2022), a microwell device to screen contraceptive agents (Small, 2019), and a prototype oligonucleotide synthesizer for in-house oligonucleotide synthesis and thereof drug screening for siRNA (Sci. Rep., 2019). We aim to explore the screening for anticancer drugs.

Nanodroplet system for high-throughput screening of antibiotic combinations

Automation microwell sytem  for screening nonhormonal contraceptive agents

Inkjet printer and microwell array for in-house oligo synthesis and screening

References:
 

  1. Hui Li, Pengfei Zhang, Kuangwen Hsieh, and Jeff Tza-Huei Wang, Combinatorial nanodroplet platform for screening antibiotic combinations, Lab on a Chip, doi.org/10.1039/D1LC00865J, 2022.

  2. Hui Li, Tyler Garner, Francisco Diaz, and Pak Kin Wong. A Multiwell Microfluidic Device for Analyzing and Screening Non-Hormonal Contraceptive Agents, Small, 15, 1901910, 2019.

  3. Hui Li#, Ye Huang#, Zewen Wei, Wei Wang, Zhenjun Yang, Zicai Liang, and Zhihong Li. An oligonucleotide synthesizer based on a microreactor chip and an inkjet printer, Scientific Report, 9, 5058, 2019. (*Co-first authors)

  4. Fangchi Shao, Pei-Wei Lee, Hui Li, Kuangwen Hsieh and Tza-Huei Wang, Emerging Platforms for High-Throughput Enzymatic Bioassays, Trends in Biotechnology, 2022.

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