Houston Methodist. Leading Medicine.
Houston Methodist. Leading Medicine

Microfluidics for Disease Diagnostics

Microfluidics for Disease Diagnostics


 
Faculty: Lidong Qin, Ph.D.

 

Problem 1: Although currently available biotechnology has provided us with a greater understanding of the molecular events in cancer, integrated microfluidic chips provide unique methodologies that can recapitulate the spatial and temporal control of cell proliferation and cell-cell/matrix communication by combining surfaces that mimic the complex biochemistries and geometries of the extracellular matrix.

Approach 1: This research focuses on developing integrated proteomic microchips to analyze cell heterogeneity using state-of-the-art bioinformatics tools and identifying metastatic signatures. The research aims are to deliver brand new technologies and methodologies capable of identifying tumor-initiating cells, discovering potential biomarkers for clinical diagnosis and targeted therapy, and identifying cancer patients with metastatic propensity.

 

Microfluidics Figure 1
Typical Microfluidics Device. (A) An autocad drawing to show our design of single cell barcode chip (SCBC). This schematic picture presents 100 horizontal channels X 36 vertical valves and creates 3600 microchambers for the single-cell experiment. Chamber number could expand to 300 X 50 = 15,000 for a PDMS device bonding to a 75 mm X 50 mm glass substrate. (B) A typical scanned protein barcode image zoomed from a portion of the SCBC device. The protein expression level from single cell or a few cell chambers is measured by fluorescent intensity shown as red bars in between green bar pairs. Yellow numbers represent cell number counted from the experiment, resulting in the barcode image.

 

Problem 2: Inspired by a global need for better diagnosis and treatment strategies, this research focuses on point-of-care (POC) challenges to ultimately design a flexible multi-platform microfluidic device for the rapid and direct characterization of rare, disease-related cells for individualized patient care.

Microfluidics Figure 2
Design of enhanced Metastasis Assessing Chip (eMAC) for rapid anti-metastasis drug tests. The design contains an engineered tissue pad made of MatrigelTM and stroma cells. It also contains cancer cell culture chambers, a drug test, and a secreted protein expression test.

 

Approach 2: We intend to globally revolutionize disease diagnosis and treatment strategies by:

  1. Fabricating selective and sensitive microfluidic devices that can detect antigens secreted by rare, disease-related cells on a single cell level at concentrations below the sub-picomolar level.
  2. Correlating amounts of secreted antigens with aggression/metastatic behaviors of the disease by on-chip quantitative analysis using fluorescence for more personalized care.
  3. Facilitating 10 or more different drug treatments simultaneously on a single microfluidic chip in 24 hours.
  4. Scaling up production, delivering devices worldwide, and commencing preclinical studies at the community level in resource-poor settings through overseas collaborations for fast delivery of cutting edge technology to those who need it most.

 

Recent Publications:

  • Shi Q, Qin L, Wei W, Feng G, Fan R, Shin YS, Guo D, Hood L, Mischel PS, Heath JR. Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells, Proc Natl Acad Sci USA. 109, 419-24 (2012).
  • Huang L, Braunschweig AB, Shim W, Qin L, Lim JK, Hurst SJ, Huo F, Xue C, Jang JW, Mirkin CA. Matrix-assisted dip-pen nanolithography and polymer pen lithography. Small. 6 (10), 1077-81 (2010).
  • Qin L, Vermesh O, Shi Q, Heath JR. Self-powered microfluidic chips for multiplexed protein assays from whole blood. Lab Chip. 9 (14), 2016-20 (2009).
  • Xu K, Qin L, Heath JR. The crossover from two dimensions to one dimension in granular electronic materials. Nat Nanotechnol. 4 (6), 368-72 (2009).
  • Banholzer MJ, Qin L, Millstone JE, Osberg KD, Mirkin CA. On-wire lithography: synthesis, encoding and biological applications. Nat Protoc. 4 (6), 838-48 (2009).

 

Current & Previous Grant Support:

  • CPRIT (R1007)
  • DOD-TATRC (W81XWH-11-02-0168)
  • U54CA149196-Pilot Project
  • Emily Herrmann Research Award
  • Golfers Against Cancer Foundation