(6do) Detection and Analysis of Biomolecules Using Diagnostic Microfluidic Systems

Goluch, E. D., University of Illinois at Urbana-Champaign

My research focuses on exploratory, multidisciplinary research in microfluidics at the system level.

Development of Diagnostic Systems: It is well known that early detection of cancer onset or recurrence increases the chances of patient survival as well as life expectancy. I have developed a single disposable chip that is capable of carrying out a multi-step process that employs nanoparticles?a biobarcode assay for cancer marker detection. The first application of the system is ultra-high sensitivity detection of prostate specific antigen to monitor recurrence of prostate cancer in patients that have undergone prostatectomy. Target analyte concentrations as low as 500 attomolar (300 total molecules) have been detected in buffer and serum samples. [4, 7] Recently, I have expanded the capabilities of the system to allow for simultaneous detection of multiple cancer markers in a single sample. In its current state, the chip-based detection scheme matches benchtop experiments in sensitivity while taking only a quarter of the time to complete. [3] My current work in this area includes modeling and optimization of the system by measuring the kinetic rates of individual steps in the process and implementing electrical detection of the final output signal.

Analysis of Lipid Bilayer Systems: The cellular membrane is the location of many biochemically and medically important processes. Ion transport, hormone signaling, blood coagulation, and endocytosis are just a few examples of the numerous important cellular processes that occur at the lipid bilayer of the membrane. These important biochemical processes are controlled by membrane receptor proteins, which are the targets of the majority of pharmaceuticals. It is therefore of great interest to develop high-throughput screening assays involving lipid bilayers and membrane-associated proteins. This requires the ability to pattern stable lipid bilayers in a defined manner. Toward this goal, in collaboration with the Sligar Group at the University of Illinois, I have developed a microfluidic method of patterning nanoscale bilayer particles known as Nanodiscs and a multiplexed assay to examine the interaction between Nanodiscs and analytes. [9]

BioMEMS for Cellular Studies: Cell motility is a complex phenomenon that enables numerous functions ranging from searching for foreign organisms to spreading of cancer cells. I have fabricated large-scale micro-contact printing stamps, which the Mrksich group at the University of Chicago uses to investigate the effect that local and global geometric cues have on the movement of cells. [10] I am also currently developing a device that will apply a force to individual cells in an array in order to study the effect on cellular adhesion and structure.

Journal Publications:

1. Ryu, K.S., Wang, X., Shaikh, K.A., Goluch, E.D., Bullen, D., Zou, J., Liu, C., Mirkin, C.A., ?Integrated Microfluidic Inking Chip for SPM Nanolithography.? Applied Physics Letters, Vol. 85, No. 1, pp. 136-138, July 5, 2004.

2. Goluch, E. D., Shaikh, K.A., Ryu, K.S., Chen, J., Engel, J.M., Liu, C. ?A Microfluidic Method for In-Situ Deposition and Precision Patterning of Thin-Film Metal on Curved Surfaces.? Applied Physics Letters. Vol. 85, No. 16, pp. 3629-3631, October 18, 2004.

3. Ryu, K.S., Shaikh, K.A., Goluch, E.D., Fan, Z., Liu, C. ?Micro Magnetic Stir-Bar Mixer Integrated with Parylene Microfluidic Channels.? Lab-on-a-Chip. Vol. 4, No. 6, pp. 608-613, November 29, 2004.

4. Shaikh, K.A., Ryu, K.S., Goluch, E.D., Nam, J.-M., Liu, J., Thaxton, C.S., Chiesl, T.N., Barron, A.E., Lu, Y., Mirkin, C.A., Liu, C. "A Modular Microfluidic Architecture for Integrated Biochemical Analysis," PNAS, vol. 102, no. 28, pp. 9745-9750, July 2005.

5. Ryu, K.S., Shaikh, K.A., Goluch, E.D., Liu, C. ?Two-terminal longitudinal hotwire sensor for monitoring the position and speed of advancing liquid fronts in microfluidic channels.? Applied Physics Letters. Vol. 88, pp. 104104-104107, March 9, 2006.

6. Chiesl, T.N., Putz, K.W., Babu, M., Mathias, P., Shaikh, K.A., Goluch, E.D., Liu, C., Barron, A.E. ?Self-Associating Block Copolymer Networks for Microchip Electrophoresis Provide Enhanced DNA Separation via ?Inchworm? Chain Dynamics.? Analytical Chemistry. Vol. 78, pp. 4409-4415, July 1, 2006.

7. Goluch, E.D., Nam, J.M., Georganopoulou, D.G., Chiesl, T.N. Shaikh, K.A., Ryu, K.S., Barron, A.E., Mirkin, C.A., Liu, C. ?A Bio-Barcode Assay for On-Chip Attomolar-Sensitivity Protein Detection? Lab-on-a-Chip. Vol. 6, pp.1293-1299, September 2006.

8. Li, S., Shaikh, K.A., Szegedi, S.S., Goluch, E.D., Liu, C. ?A Micromachined Inking Chip for Scanning Probe Nanolithography Using Local Thermal Vapor Inking Method.? Applied Physics Letters. Vol. 89, pp.173125-173128, October 26, 2006.

9. Goluch, E.D., Shaw, A.W., Sligar, S.G., Liu, C. ?Parallel Patterning and Analysis of Lipid Bilayer Nanodiscs using a Microfluidic Grid.? NanoLetters. (in preparation).

10. Maduram, J., Goluch, E.D., Liu, C., Mrksich, M. ?Local and Global Geometric Cues in the Adhesive Microenvironment Modulate Cytoskeletal Architecture and Cell Polarity.? PNAS. (in preparation).