Optics-Integrated Microfluidic Platforms for Biomolecular Analyses

Abstract

Compared with conventional optical methods, optics implemented on microfluidic chips provide small, and often much cheaper ways to interrogate biological systems from the level of single molecules up to small model organisms. The optical probing of single molecules has been used to investigate the mechanical properties of individual biological molecules; however, multiplexing of these measurements through microfluidics and nanofluidics confers many analytical advantages. Optics-integrated microfluidic systems can significantly simplify sample processing and allow a more user-friendly experience; alignments of on-chip optical components are predetermined during fabrication and many purely optical techniques are passively controlled. Furthermore, sample loss from complicated preparation and fluid transfer steps can be virtually eliminated, a particularly important attribute for biological molecules at very low concentrations. Excellent fluid handling and high surface area/volume ratios also contribute to faster detection times for low abundance molecules in small sample volumes. Although integration of optical systems with classical microfluidic analysis techniques has been limited, microfluidics offers a ready platform for interrogation of biophysical properties. By exploiting the ease with which fluids and particles can be precisely and dynamically controlled in microfluidic devices, optical sensors capable of unique imaging modes, single molecule manipulation, and detection of minute changes in concentration of an analyte are possible.

Figure 1

Physical configuration of variable focus lenses. (A) Pneumatically tuned lens. (B) Lens controlled by electrowetting. (C) Hydrodynamic lens. (D) Environmentally responsive lens. Dashed lines indicate approximate limits of physical tunability. ITO, indium tin oxide. To see this figure in color, go online.

Figure 2

Single influenza virus particle detection. (A) The incorporation of both solid-core (orange) and liquid-core (blue) ARROW waveguides allow small volume optical excitation of fluorescent virus particles, whereas virus particle transversal of a nanopore results in transient drops in current. (B) Particles pass first through the nanopore, over which current changes are measured (top, black) and then through optical detection volume, where fluorescence signals from viruses (red) and nanoparticles (blue) are measured, resulting in a known dwell time. Blockade depths from both types of particles are very similar, but variable dwell times allow them to be distinguished. The incorporation of both optical and electrical detectors enables the separation of single viruses from a mixture of nanobeads and viruses (81). This is an unofficial adaptation of an article that appeared in an ACS publication. ACS has not endorsed the content of this adaptation or the context of its use. http://pubs.acs.org/doi/full/10.1021/nl502400x. To see this figure in color, go online.

Figure 3

Principle of WGM sensors. Light from a laser (red) is evanescently coupled into the dielectric toroid, sphere, cylinder, ring, or disk via a light guide, such as a tapered optical fiber. The wavelength of the laser is tuned so that the light traveling around the surface of the WGM remains in phase when it returns back to the point of coupling. As the resonant wavelength is approached, power is extracted from the fiber, decreasing the amount of light transmitted to the detector. When analytes (orange) are bound to the sensing surface through antibodies (green), the resonant wavelength of the system shifts due to local changes in the index of refraction. Resonance shifts down to 6 fm can be detected with appropriate detectors (90). To see this figure in color, go online.

Figure 4

Optofluidic human blood immunoanalysis. (A) Schematic of optofluidic device. (B) System functional states during optofluidic ELISA. (C) Scanning electron microscopy image of cells conjugated to microbeads trapped by micropillar array in the microfluidic chamber. (D) Representative readout from LSPR experiment (141). This is an unofficial adaptation of an article that appeared in an ACS publication. ACS has not endorsed the content of this adaptation or the context of its use. http://pubs.acs.org/doi/full/10.1021/nn406370u. To see this figure in color, go online.