Research Interests

Pulmonary diseases (e.g. asthma, cystic fibrosis, COPD, lung cancer, and COVID-19) are profoundly impacting our society. In pulmonary microfluidic lab, we integrate the cutting-edge micro-engineering tools (e.g. microfluidics, organ-on-a-chip) with biology to understand airway physiology, treat pulmonary disease, and eventually improve human health. Specifically, we concentrate our efforts on the following aspects.

  • Innovate lab-on-a-chip system that integrates fluids, mechanics, and biology.
  • Apply microfluidic methods to study pathogenesis, diagnosis, and therapeutics of pulmonary disease.
  • Translate scientific discoveries and engineering innovations from bench to bedside.

Research Achievements

 

Microfluidic analysis of submucosal gland mucus.

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Submucosal glands secrete most mucus in human trachea and bronchi. However, investigating biochemical properties of submucosal gland mucus is challenging due to its tiny volume (i.e. ~1 nL from each gland), high viscoelasticity, and under modifications by the airway surface. To tackle this challenge, we developed microfluidic methods to form, collect, transfer, and analyze the composition of mucus secreted from individual glands. We applied this platform to study mucus in cystic fibrosis, a life-shortening, genetic disease that destroys the lung. We revealed that mucus from cystic fibrosis glands is more acidic and protein concentrated due to loss of CFTR function. This method also provides potential to investigate secretion in many other glands and diseases.

  • Xie Y.*, Lu L.*, (* Equal contribution) Tang X. X., Moninger T. O., Huang T. H., Stoltz D. A., Welsh M. J. (2020), Acidic Submucosal Gland pH and Elevated Protein Concentration Produce Abnormal Cystic Fibrosis Mucus, Developmental Cell, https://doi.org/10.1016/j.devcel.2020.07.002.

Microfluidic model of mucus production and clearance.

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The lung keeps sterile by trapping inhaled pathogens and particles with airway mucus, and sweep them up the airway with mucociliary transport. In cystic fibrosis (CF) lung disease, mucus strands, secreted from submucosal glands, fail to detach from the airway surface. Impaired mucus detachment causes defective mucociliary transport, initiates a cascade of infection, inflammation, and severe lung disease of CF. However, the underlying mechanism of a defective mucociliary transport in CF remains unclear. To elucidate its mechanism, we invented a microfluidic model of submucosal glands to reconstruct mucus production and clearance on-chip. We revealed that acidic mucus strands in CF resist stretching and breakage from gland ducts. This work demonstrates the mechanism of defective mucociliary transport in CF, and identifies submucosal glands as a potential target for CF lung disease treatment.

  • Xie Y.*, Lu L.*, (* Equal contribution) Tang X. X., Moninger T. O., Huang T. H., Stoltz D. A., Welsh M. J. (2020), Acidic Submucosal Gland pH and Elevated Protein Concentration Produce Abnormal Cystic Fibrosis Mucus, Developmental Cell, https://doi.org/10.1016/j.devcel.2020.07.002.
  • Xie Y., Ostedgaard L., Alaiwa M.H.A., Lu L., Fischer A.J., Stoltz D.A., (2018), Mucociliary Transport in Healthy and Cystic Fibrosis Pig Airways, Annals of the American Thoracic Society, 15, S171-S176.

Acoustofluidic particle and cell manipulation.

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Manipulation of particles and cells in microfluidic devices is imperative but extremely difficult due to laminar flow nature and inaccessibility of the microfluidic chamber. We developed an optothermally-generated, acoustic-actuated system that overcomes laminar flow limitation to manipulate particles/cells. We harnessed the energy from optothermal effect to form a vapor bubble and actuated with acoustic wave to collect, transport, and architect microparticle assemblies pattern. In addition, the acoustic actuated bubbles were applied to detect deformability of individual cells for diagnosis. We demonstrated that cancer cells have a larger deformability than normal cells due to loss of cytoskeleton structure. These techniques set a new methodology for non-invasive, automated, low-cost, and easy-to-use on-chip manipulation.

  • Xie Y., Nama N., Li P., Mao Z., Huang P.H., Zhao C., Costanzo F., and Huang T.J. (2016). Probing cell deformability via acoustically actuated bubbles, Small, 12(7), 902-910.
  • Xie Y.*, Zhao C.*, (*Equal Contributions), Zhao Y., Li S., Rufo J., Yang S., Guo F., and Huang T.J. (2013) Optoacoustic tweezers: a programmable, localized cell concentrator based on opto-thermally generated, acoustically activated, surface bubbles, Lab on a Chip, 13, 1772-1779.

Acoustofluidic fluids manipulation.

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Manipulating flow components for with a pre-defined manner is important for microfluidic chemical detection, medical diagnosis, and additive manufacturing. However, it requires techniques that can overcome laminar flow with spatial and temporal resolution. To address this challenge, we utilize the oscillation of a micro-sized bubble for mixing, extraction and biochemical reactions of liquid components in a microfluidic chamber. In addition, with a team of collaborators, we completed research projects dealt with acoustic-actuated sharp-edged structures. Particularly, acoustic wave is applied to oscillate sharp-edges in order to control the flow and then facilitate mixing, pumping, forming chemical gradient, and trigger sputum liquefaction reactions.

  • Xie Y., Chindam C., Nama N., Yang S., Lu M., Zhao Y., Mai J.D., Costanzo F., and Huang T.J. (2015). Exploring bubble oscillation and mass transfer enhancements in acoustic-assisted liquid-liquid extraction with a microfluidic device, Scientific Reports, 5, 12572.
  • Xie Y., Ahmed D., Lapsley M.I., Lin S.C.S., Nawaz A.A., Wang L., and Huang T.J. (2012), Single-shot characterization of enzymatic reaction constants Km and kcat by an acoustic-driven, bubble-based fast micromixer, Analytical Chemistry, 84 (17), 7495-7501.
  • Huang P.H., Xie Y., Ahmed D., Rufo J., Nama N., Chen Y., Chan C.Y. and Huang T.J. (2013). An acoustofluidic micromixer based on oscillating sidewall sharp-edges, Lab on a Chip, 13, 3847-3852.
  • Ozcelik A., Ahmed D., Xie Y., Nama N., Qu Z., Nawaz A.A., Huang T.J. (2014), An acoustofluidic micromixer via bubble inception and cavitation from microchannel sidewalls, Analytical chemistry, 86(10), 5083-5088.

Optothermal effect based microfluidic applications.

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Optothermal effect, a solid-state surface or nanostructure can turn into a micro/nano heating source under laser illumination, allows for non-invasive control of heat at the micro/nanoscale. In the presence of a liquid, a surface bubble can be generated on top of the solid surface or nanostructure at a temperature much higher than the boiling point of the liquid. The high temperature and the fluid flow associated with the optothermally generated surface bubble enable many intriguing applications, ranging from the micro/nano-manipulation of fluids, particles, cells, and light to the synthesis of micro/nano-structures under ambient conditions.

  • Yuliang Xie, Chenglong Zhao, An optothermally generated surface bubble and its applications, Nanoscale, 2017, 9, 6622-6631.
  • Chenglong Zhao*, Yuliang Xie* (* Equal contribution), Zhangming Mao, Yanhui Zhao, Joseph Rufo, Shikuan Yang, Feng Guo, John D. Mai and Tony Jun Huang, Theory and experiment on particle trapping and manipulation via optothermally generated bubbles, Lab on a chip, 2014,14, 384-391.
  • Yuliang Xie*, Shikuan Yang* (* Equal contribution), Zhangming Mao, Peng Li, Chenglong Zhao, Zane Cohick, Po-Hsun Huang, and Tony Jun Huang, In-Situ Fabrication of 3D Ag@ZnO Nanostructures for Microfluidic Surface-Enhanced Raman Scattering Systems, ACS Nano, 2014, 8 (12), 12175–12184.