We are currently looking for a postdoctoral researcher in the field of optics, optofluidics, and biophotonics. Strong applicants with the Ph.D. in optical engineering, mechanical engineering, electrical engineering, physics, biophysics, and related fields are encouraged to apply. The successful candidate will have ample opportunities to participate in high-impact, translational biomedical research projects in collaboration with bioengineers and clinical scientists at the top-ranked University of Michigan College of Engineering and Medical School.

Please send your CV to Prof. Kurabayashi (katsuo@umich.edu).

We are currently looking for a postdoctoral researcher in the field of optics, optofluidics, and biophotonics. Strong applicants with the Ph.D. in optical engineering, mechanical engineering, electrical engineering, physics, biophysics, and related fields are encouraged to apply. The successful candidate will have ample opportunities to participate in high-impact, translational biomedical research projects in collaboration with bioengineers and clinical scientists at the top-ranked University of Michigan College of Engineering and Medical School.

Please send your CV to Prof. Kurabayashi (katsuo@umich.edu).

Micro-instrumentation for Colon Cancer Molecular Imaging

Sponsor: NIH National Cancer Institute

According to the national statistics, risk factors of cancer are high for human digestive tract organs. In particular, colon cancer is the 2^nd largest cause of death in the U.S. The mission of our research is to develop novel optical imaging technologies for the early detection of colon cancer. The conventional endoscopic method based on white light imaging often fails to detect the early onset of the disease on a flat tissue surface. Crypts in the colon experience morphological changes during the development of tumors. To precisely capture the onset of cancer, we need to obtain the cross-sectional image of crypts with molecular-level selectivity between the normal tissue and the premalignant tissue.

We take a confocal microscopy imaging technique for our medical imaging. The left figure shows a conventional single axis configuration, where a high NA objective lens is used to achieve sub-cellular resolution, and the focal point is scanned using a scanning mirror. But it limits the size of the field of view, preventing us from obtaining the pathologically important cross-sectional view of tissue. Instead, we use a novel dual axes architecture that uses separate, low NA objectives to achieve both sub-cellular resolution and long working distance.  Post-objective scanning provides a large field-of-view and instrument scalability to millimeter dimensions.  With this architecture, we aim to obtain a vertical (V) cross-sectional image while reducing the collection of light scattered by tissue (dashed orange lines).

We use MEMS technology to construct the micro confocal endoscope for in vivo optical imaging. A MEMS micro mirror scanner is used for the post-objective scanning of the illumination and emission lights in the horizontal direction. In order to achieve the vertical scanning, we use a novel z-axis microactuator consisting of multiple metal-PZT film stacks. Prof. Kenn Oldham’s group is leading our effort to develop this z-axis microactuator and integrate it into the endoscope packaging. As a result of our instrumentation research, we expect that we can enable optical biopsy of colon tissue eliminating the need for physically removing a tissue sample form a patient.

Our medical school colleagues (Prof. Tom Wang’s group) are currently working on identifying molecular probes used for the optical imaging. These probes are called peptides, which are fragments of protein molecules. They are expressed by bacteria called M13 phage. A library of M13 phages provides 10¹² peptide species with known amino acid sequences. Our colleagues are selecting peptides which can preferentially bind to precancerous tissue surfaces as molecular probes using a technique called biopanning.

References:

Tung, Y.-C., and Kurabayashi, K., “A Metal-Coated Polymer Micromirror for Strain-Driven High-Speed Multi-Axis Optical Scanning,” IEEE Photonics Tech. Lett., vol. 17, pp. 1193-1195, 2005.

Tung, Y.-C., and Kurabayashi, K., “A Single-Layer PDMS-on-Silicon Hybrid Micro Actuator with Multi-Axis Out-of-Plane Motion Capabilities: Part I: Modeling and Design,” J. Microelectromechanical Systems., vol. 14, pp. 548- 557, 2005.

Tung, Y.-C., and Kurabayashi, K. “A Single-Layer Multiple Degree-of-Freedom PDMS-on-Silicon Dynamic Focus Micro-lens,” Proc. the 19^h IEEE Micro Electro Mechanical Systems, Istanbul, Turkey, pp. 838-841, Jan. 22 – 26, 2006.

Hsiung, P.-L., Hardy, J., Friedland, S., Soetikno, R., Du, C.B., Wu, A.P., Sahbaie, P., Crawford, J.M, Lowe, A.M., Contag, C.H., and Wang, T.D., “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nature Medicine, vol. 14, pp. 454-458, 2008.

Vapor Thermal Modulation for 2D Gas Chromatography

Sponsor: NASA, NSF ECCS, Agilent Technologies

The NASA astrobiology program has a primary mission to explore organic signatures on extraterrestrial bodies within the solar system. Microchip-based comprehensive two-dimensional gas chromatography (GCxGC) coupled with mass spectroscopy provides a promising means for the NASA to achieve this mission with limited resources. This project aims to develop a key subcomponent of the microfabricated GCxGC system, a thermal modulator (TM), using MEMS technology. The TM is a crucial device to achieve high sensitivity in the GCxGC system by providing 10-to-50-fold detection enhancement. It produces very narrow injection plugs for very rapid second-column separations. The MEMS device developed in this project is integrated with microfabricated GC columns and generates heating and cooling cycles between -50°C and 250°C over short timescales (~500-1000 ms). Significant technological advances are being explored to reduce space, mass, and power resources required for the organic vapor separation process with the MEMS-based TM device. The system incorporating the TM provides the opportunity to conduct complex in situ sample analysis with minimal temperature control requirements.

Optical and scanning electron microscopy (SEM) images of microscale thermal modulator and its packaging with an environmental chamber on a printed circuit board (Left). The device placed at the junction between the 1^st and 2^nd columns modulates 1^st dimensional vapor chromatograms to dissect them into several sharp peaks injected to the 2^nd column (right).

References:

Kim, S.-J., Reidy, S.M, Block, B., Wise, K.D., Zellers, E.T., and Kurabayashi, K., “Microfabricated Thermal Modulator for Comprehensive Two-Dimensional Micro Gas Chromatography: Design, Thermal Modeling, and Preliminary Testing,” Lab Chip, 10, 1647-1654, 2010.

Kim, S.-J., Reidy, S.M., Block, B.P., Wise, K.D., Zellers, E.T., and Kurabayashi, K., “A low power, high-speed miniaturized thermal modulator for comprehensive 2D gas chromatography,” Proc. the 23^rd International Conference on Micro Electro Mechanical System, MEMS 2010, Hong Kong, pp. 124-127, January 24-28, 2010.

Microsystems for Fluorescent Spectroscopy of Cells

Sponsor: NSF ECCS

Light emitted from fluorescent proteins and nanomaterials provides important information for biologists to elucidate genetic transcription in cells, protein bindings at cell membranes, and, molecular-level physiological properties of tissue. A technological breakthrough in biophotonics and molecular imaging significantly advances scientific knowledge leading to drug discovery and disease prevention. This research has developed a novel device for the purpose of establishing a miniature biophotonic flow cytometry technology for point-of-care disease diagnostics. Our device consists of a soft grating material repeatedly stretched by a micromachine fabricated on a silicon chip and is optically coupled with the interrogation zone of a microfluidic flow channel device. Changing its light dispersing property with mechanical strain, the soft material permits very fast and sensitive wavelength tuning for spectral differentiation of fluorescently labeled biological particles flowing through the channel. The research team aims to extend this technology to precisely differentiate prostate cancer stem cells, which state-of-the-art cancer biology research has identified as highly suspected culprits of the life-threatening disease.

SEM image of on-chip strain-tunable soft polymer nano-grating optical filter. The device is coupled with a microfluidic chamber via an optical fiber to achieve high-speed, high-sensitivity fluorescence spectral acquisition for detecting fluorescently labeled cells and biophotonic particle flows.

Illustrations of the device operation for spectroscopic measurements.  (a) The MEMS comb drive actuators stretch the elastomeric grating causing the optical diffraction angle to dynamically vary. The slit in front of the detector only allows the intensity of a narrow spectral band of the dispersed light to be detected. (b) Image of the microbridge with grating imprint at initial state. (c) Image of the microbridge stretched to alter the grating spacing.

References:

Y.-C. Tung and K. Kurabayashi, “Nanoimprinted Strain-Controlled Elastomeric Gratings for Optical Wavelength Tuning,” Appl. Phys. Lett., 86, 161113 2005.

S.C. Truxal, Y.-C. Tung, and K. Kurabayashi, “High-speed deformation of soft lithographic nanograting patterns for ultrasensitive optical spectroscopy,” Appl. Phys. Lett., 92, 051116, 2008.

S.C. Truxal, Y.-C. Tung, and K. Kurabayashi, “A flexible nanograting integrated onto silicon micromachines by soft lithographic replica molding and assembly,” IEEE J. Microelectromechanical Systems, 17, 393- 401, 2008.

N.-T. Huang, S.C. Truxal, Y.-C. Tung, A. Hsiao, S. Takayama, and K. Kurabayashi, “High-speed tuning of visible laser wavelength using a nanoimprinted grating optical tunable filter,” Appl. Phys. Lett., 95, 211106, 2009.

Biomolecular Motor Nanotechnology/BioMEMS Immunoassay

Sponsor: DARPA, NSF CBET, Coulter Foundation

In recent years, biomolecular motors (BMMs) – highly efficient molecular machines that nature has evolved for over millions of years – have been employed in miniaturized analysis systems and play important roles in bionanotechnology applications, such as biosensing, molecular sorting, fluidic pumping, micromechanical powering, and molecular assembly. They are compact with a nanometer size, yield robust movement in a fluidic environment, and are readily fueled by adenosine triphosphate (ATP) containing solution. This eliminates the need for an external energy source for micro/nanofluidic actuation. In addition, BMMs efficiently manipulate individual biological molecules and proteins, making possible the development of a motor protein-based biosensing system with a nanoscale mass transport/concentration function.

This research aims to develop a new biosensing chip technology, namely the biomolecular motor (BMM) smart microarrays, which allows high-throughput, ultrasensitive (at attomolar concentrations) biosensing for multiplexed on-chip protein binding assays. Incorporating a BMM-based mass transport/sensing mechanism in a microfluidic system, the BMM smart microarrays enable autonomous sample handling that involves specific binding, sorting, transporting, and concentrating of multiple target analytes via kinesin motor protein-driven microtubules. The proposed method combines biomolecular motors, photonics and nanofluidics in a single biosensor to simultaneously transport and concentrate large numbers of molecular analytes (10 – 100) to specific detectors for ultra-sensitive quantification.

Design of biomolecular motor-based detector cell. (a) Schematic overview and SEM image of the detector cell, (b) Detailed structure and functional concept of the collector region of the cell. Bioconjugated microtubules land in the sorter regions and are transported by kinesin toward the collector region. (c) Representative time sequence demonstrating the rapid collection of microtubules in the detector cell. After 40 min of operation, the MT density in the collector region (d) is approximately 2 orders of magnitude higher than that on bare glass without microstructures. This microtubule concentrating effect is quantitatively demonstrated in (d) by comparing the microtubule density in our microfabricated detector cell with a bare glass surface as a function of time.

References:

C.T. Lin, M.T. Kao, K. Kurabayashi, and E. Meyhofer, “Self-contained biomolecular motor-driven protein sorting and concentrating in an ultrasensitive microfluidic chip” Nano Lett., 8, 1041-1046, 2008.

C.T. Lin, M.T. Kao, E. Meyhofer, and K. Kurabayashi, “Surface Landing of Microtubule Nanotracks Influenced by Lithographically Patterned Channels,” Appl. Phys. Lett., 95, 103701, 2009.

C.T. Lin, E. Meyhofer, and K. Kurabayashi, “Predicting the stochastic guiding of kinesin-driven microtubules in microfabricated tracks: A statistical-mechanics-based modeling approach,” Phys. Rev. E., 81, 011919, 2010.