Integrated Optofluidics: Manipulation and Analysis Single Molecules on a Chip

Optofluidics is a rapidly emerging area of research that can be described as "the combination of both integrated optical and fluidic components in the same miniaturized system". Optofluidics holds great promise for novel devices for biomedical instrumentation, analytical chemistry and other fields that deal with liquid analytes. A major thrust in the field is to use integrated optics to replace the bulky microscopy analysis that is still commonly in use. This will enable a fully planar, fully integrated lab-ona-a-chip on which signal, electronics, and fluids run in the plane of the chip. The Applied Optics group has led the field planar integrated optofluidics wiith the development of liquid-core ARROW waveguides that allow for using integrated optics technology in conjuction with microfluidics. The W.M. Keck Center for Nanoscale Optofluidics was recently established at UCSC to catalyze interdisciplinary research that advances and uses waveguide-based chips.

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]
  • single virus detection on a chip [7]
  • waveguide loss measurement technique based on optically induced particle motion [8]
  • planar on-chip all-optical particle trap [9] and particle [10]
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. Similar measurements have now been demonstrated on viruses (Q-beta baxteriophages), again resulting in single particle sensitivity via FCS [7].

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

Particle manipulation

It is well known that momentum transfer from photons onto solid objects result in optical forces. These can be used to optically manipulate micro- and nanoscale particles, the best-known example being the laser tweezers that are routinely being used in cell biology and other fields. We are studying optofluidic implementations of optical forces using liquid-core waveguides.

One example is the use of optical particle manipulation for waveguide characterization [8]. Fig. 3 shows a microbead propelled through a liquid-core waveguide channel by the scattering force that the optical mode exerts on it. The force is proportional to the power at any given particle position, determining the velocity as the particle moves along. Thus, the waveguide loss which reduces the available power can be extracted by recording the particle’s position as it moves along the channel (see Fig. 3). If the particle position is also tracked laterally, the lateral mode structure can be extracted from the particle histogram (Fig. 3). These measurements show that optical particle manipulation can be used as a simple, rapid, and non-destructive means for hollow-core waveguide characterization.

Fig. 3: Waveguide characterization using optical forces. Top left: time-dependent position of an optically propelled microbead; bottom left: time-dependent particle position along waveguide channel; right: histogram of lateral position and match with waveguide mode calculations.

A second example for the use of optical forces for particle manipulation is the development of a novel all-optical dual beam trap [9,10]. The concept is shown in Fig. 4. Two counterpropagating beams are sent through the waveguide. Unlike a conventional dual beam trap, the scattering force exerted by the two beams is asymmetric because of the presence of waveguide loss which results in an asymmetry in power distribution. At one point along the waveguide, the longitudinal forces are equal and a particle can be trapped. The figure also shows a microscope image of two simultaneously and independently trapped microbeads, one using the new loss-based dual beam trap and one using a more traditional dual beam trap (see [9] for details). The trapping architecture is compatible with simultaneous fluorescence detection of the trapped objects and has enabled us to carry out prolonged interrogations of microbeads and E.coli bacteria.

Fig. 4: Loss-based all-optical dual beam trap. Left: schematic of applied beams; right: microscope image of two microbeads trapped in planar, on-chip trap.

The scattering forces responsible for creating the trapping potential act along the entire waveguide channel. Thus, if multiple particles are present, they are all subject to these optical forces and can be driven towards a single trapping location. This concept can be used to create an all-optical particle concentrator which enhances the particle concentration locally at a desired point [10]. This concept is shown in Fig. 5 which shows a large increase in fluorescence signal as >100 fluorescent microbeads are optically accumulated and trapped in the waveguide intersection.
Fig. 5: Optofluidic particle concentrator (a) Concentrated 1µm particles at a waveguide intersection. (b) A particle ensemble transported to the far end of the hollow waveguide through the application of an additional electric field. (c) Temporal evolution of the fluorescence signal during the optical concentration of 500nm particles. Insets show fluorescence snapshots of a single particle and the final particle ensemble.
 

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.

[7] M.I. Rudenko, S. Kühn, E.J. Lunt, D.W. Deamer, A.R. Hawkins and H. Schmidt, " Ultrasensitive Q? Phage Analysis Using Fluorescence Correlation Spectroscopy on an Optofluidic Chip", Biosensors and Bioelectronics, 24, 3258-3263 (2009).

[8] P. Measor, S. Kühn, E.J. Lunt, B.S. Phillips, A.R. Hawkins, and H. Schmidt, "Hollow-core Waveguide Characterization by Optically Induced Particle Transport", Optics Letters, 33, 672-674 (2008).

[9] S. Kühn, P. Measor, E.J. Lunt, B.S. Philips, D.W. Deamer, A.R. Hawkins, and H. Schmidt, “Loss-based optical trap for on-chip particle analysis”, Lab Chip 9, 2212 (2009).

[10] S. Kühn, E.J. Lunt, B.S. Philips, A.R. Hawkins, and H. Schmidt, “Optofluidic particle concentration by a long-range dual-beam trap”, to appear in Optics Letters (2009).

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Integrated Optofluidics

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