Richard A. Flynn

Optical Manipulation of Objects and Biological Cells in Microfluidic Devices

In this paper, we review optical techniques used for micro-manipulation of small particles and cells in microfluidic devices. These techniques are based on the objects interaction with focused laser light (consequential forces of scattering and gradient). Inorganic objects including polystyrene spheres and organic objects including biological cells were manipulated and switched in and between fluidic channels using these forces that can typically be generated by vertical cavity surface emitting laser (VCSEL) arrays, with only a few mW optical powers. T-, Y-, and multi-layered X fluidic channel devices were fabricated by polydimethylsiloxane (PDMS) elastomer molding of channel structures over photolithographically defined patterns using a thick negative photoresist. We have also shown that this optical manipulation technique can be extended to smaller multiple objects by using an optically trapped particle as a handle, or an “optical handle”. Ultimately, optical manipulation of small particles and biological cells could have applications in biomedical devices for drug discovery, cytometry and cell biology research.

Parallel transport of biological cells using individually addressable VCSEL arrays as optical tweezers

We have demonstrated the use of vertical cavity surface emitting lasers (VCSELs) for optical trapping and active manipulation of live biological cells and microspheres. We have experimentally verified that the Laguerre‐Gaussian laser mode output from the VCSEL functions just as well as the traditional Gaussian fundamental laser mode for optically trapping biological cells and may be preferable since the highest intensity of the Laguerre‐Gaussian mode is located at the outer ring of the optical aperture, which allows for stronger optical confinement to be obtained for a lower total power. Another advantage that VCSELs have over conventional gas and diode lasers is their ability to be manufactured in an array form. Using a 2 � 2 array of VCSELs, the simultaneous and independent transport of four human red blood cells is demonstrated indicating that much larger two-dimensional VCSEL arrays can be used as individually addressable optical tweezers in biological chips and systems. This parallel transport capability will have a significant impact in currently developing biochip array and assay technologies through the facilitation of the selection, relocation, and precision placement of cells. # 2002 Elsevier Science B.V. All rights reserved.

VCSEL Arrays as Micromanipulators in Chip-Based Biosystems

The potential use of vertical cavity surface emitting laser (VCSEL) arrays for applications in cell analysis and tissue engineering is investigated by means of parallel optical trapping and active manipulation of biological cells on microfluidic chips. The simultaneous and independent transport of nine cells using a 3×3 array of VCSELs has been demonstrated experimentally; indicating that larger 2-dimensional array transport using individually addressable tweezers is achievable with VCSEL array devices. The transport properties of VCSEL tweezers have been investigated for various types of cells including 3T3 Murine fibroblasts, yeast, rat primary hepatocytes and human red blood cells. Due to the low relative index of refraction between the biological cell and surrounding medium and the relatively low optical power available with present VCSELs, the Laguerre-Gaussian laser mode output of the VCSEL is more favorable to use in an optical tweezer since the highest intensity is located at the outer ring of the optical aperture, producing stronger optical confinement at lower power levels. For larger biological cells or cells with a lower relative index of refraction, the power limitations of a single VCSEL were overcome through the binning of several VCSELs together by combining the outputs of a sub-array of VCSELs into a collective optical tweezer. A comprehensive analysis and simulation of how the VCSELs’ pitch and output beam divergence influence the operation of the resultant optical tweezer array is presented along with our experimental data. Employing the methods of parallel array transport and the binning of multiple VCSEL outputs, allows for the manipulation and spatial arrangement of different types of cells in a co-culture so as to facilitate the formation of engineered tissues.

Optical Manipulation of Objects in Microfluidic Devices

In this paper, we present object manipulation methodologies in microfluidic devices based on object-photon interactions. Devices were fabricated by polydimethylsiloxane (PDMS) elastomer molding of channel structures over photolithographically defined patterns using a thick negative photoresist. Inorganic objects including polystyrene spheres and organic objects including live cells were transferred into fluidic channels using a syringe pump. The objects were trapped and manipulated within the fluidic channels using optical tweezers formed by VCSEL arrays, with only a few mW of optical power. We have also shown that it is possible to manipulate multiple objects as a whole assemble by using an optically-trapped particle as a handle, or an “optical handle”. Optical manipulation will have applications in biomedical devices for drug discovery, cytometry and cell biology research.

Superresolution Using a Vertical-Cavity Surface-Emitting Laser (VCSEL) with a High-Order Laguerre-Gaussian Mode.

A vertical-cavity surface-emitting laser (VCSEL) is current-annealed to operate in the high order (0, 4) Laguerre mode, and this source is used in a superresolution setup to achieve a spot size smaller than the classical diffraction limit. Theory predicts a reduction down to 51% of the classical limit in each dimension (i.e. 4× reduction in area), and a reduction down to 65% (i.e. 2.5× reduction in area) is experimentally demonstrated with a signal-to-noise ratio of >10 dB between the main-lobe and the side-lobe intensities.

Using optical forces for the characterization of biological cell activities

Optical forces successfully manipulate biological cells and measure small forces such as molecular binding forces. This paper focuses on the use of optical forces for the direct characterization of various activities of biological cells

Application of VCSEL's to a range of bioengineering assays

Vertical cavity surface emitting lasers (VCSEL) have been used for variety of applications including data storage, data readout, detection, and optical interconnects. Here, we present the application of VCSELs for manipulation and sorting of live cells.