Integrated Optofluidics: Detecting and Analyzing Single Molecules on a Chip

Optofluidics describes the combination of optics and microfluidics and holds great promise for novel devices for biomedical instrumentation, analytical chemistry and other fields that deal with liquid analytes. A highly desirable extension of optofluidics is to use integrated optics to replace the bulky microscopy analysis that is still commonly in use. This would allow to develop a fully planar, fully integrated lab on a chip on which optical signal, electronics, and fluids run in the plane of the chip. The Applied Optics group has led the field of planar integrated optofluidics with the development of liquid-core ARROW waveguides that allow for using integrated optics technology in conjunction with microfluidics.

Our research emphases include:
  • Development of liquid-core waveguides
  • Single molecule detection and analysis
  • Use of integrated optics in molecular biology
  • Optical particle manipulation and control on an optofluidic chip

Recent breakthroughs achieved by our group include:
  • light guiding in liquid core (LC) ARROW waveguides [1]
  • efficient fluorescence generation and collection in LC-ARROWs [2]
  • single molecule fluorescence sensitivity using planar detection on a chip [3]
  • fluorescence correlation spectroscopy on a chip [4]
  • surface-enhanced Raman detection on a chip [5]
  • single bioparticle analysis on a chip [6]

Fig. 1 shows cross sections of micron-scale liquid core waveguides that use dielectric multilayers to confine light in the hollow channel. Fabrication is fully compatible with silicon processing technology and developed by our collaborators, the Micro-Technologies Group of Aaron Hawkins at Brigham Young University. The use of small cross sections is a key requirement for creating the small optical excitation volumes that are necessary to achieve single molecule detection.

Fig. 2 shows a schematic of the optofluidic principle. Molecules are moved electrokinetically through liquid-core ARROW. They are optically excited via an intersecting solid-core waveguide. Emitted light is collected by the LC-ARROW in the plane of the chip and guided to the chip edge after being coupled to another solid-core waveguide. Also shown is a trace of fluorescence bursts from single liposomes that are passing the waveguide intersection. The signal can be analyzed with various methods to yield information about the concentration and properties of the detected biomolecule.

We are currently pursuing several future directions, most notably new types of optical waveguides, implementation of advanced optical detection techniques, addition of electrical and optical control of single biomolecule, analysis of RNA translation in single ribosomes, and further integration towards self-contained, highly parallel optofluidic detection systems.

This work is funded by the National Institute of Health (NIH/NIBIB), the W.M. Keck Foundation, the National Academy of Sciences, the National Science Foundation (NSF), and the NASA University Affiliated Research Center. We collaborate with the groups of David Deamer (Biomolecular Engineering, UCSC), Harry Noller (Molecular Biology, UCSC), Jin Zhang (Chemistry, UCSC), Vahid Sandoghdar (ETH Zurich), and Aaron Hawkins (BYU).

[1] D. Yin, J.P. Barber, A.R. Hawkins, D.W. Deamer, and H. Schmidt, "Integrated optical waveguides with liquid cores", Applied Physics Letters, 85, 3477, (2004). (1986).

[2] D. Yin, J.P. Barber, A.R. Hawkins, and H. Schmidt, "Highly efficient fluorescence detection in picoliter volume liquid-core waveguides", Applied Physics Letters, 87, 211111 (2005).

[3] D. Yin, J.P. Barber, D.W. Deamer, A.R. Hawkins, and H. Schmidt, "Single-molecule detection sensitivity using planar integrated optics on a chip", Optics Letters 31, 2136 (2006).

[4] D. Yin, E.J. Lunt, A. Barman, A.R. Hawkins, and H. Schmidt, "Microphotonic control of single molecule fluorescence correlation spectroscopy using planar optofluidics" Optics Express 15, 7290 (2007).

[5] P. Measor, L. Seballos, E.J. Lunt, D. Yin, J.Z. Zhang, A.R. Hawkins, and H. Schmidt, "On-chip Surface-enhanced Raman scattering (SERS) detection using integrated liquid-core waveguides", Appl. Phys. Lett. 90, 211107 (2007).

[6] D. Yin, E.J. Lunt, M.I. Rudenko, D.W. Deamer, A.R. Hawkins, and H. Schmidt, "Planar optofluidic chip for single particle detection, manipulation, and analysis", Lab on Chip 2007, DOI: 10.1039/b708861b.

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Integrated Optofluidics

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