Hua Shao

Single-Cell Detection Using Optofluidic Intracavity Spectroscopy

Optofluidic intracavity spectroscopy was used to realize label-free detection of single biological cells, including yeast cells and human blood cells, as well as polystyrene spheres in a microfluidic Fabry-Perot cavity. The design, fabrication, and testing of the cavities are discussed, along with the sensing mechanism. The resonant conditions of the microfluidic cavity were modified by the cells and microspheres inside the cavity due to the effective refractive index profile of the cells. Transmission spectra of single cells in the cavity, measured using a customized microscope system, exhibited cell-type specific higher order transverse mode features, including the number of transverse modes, mode shape, and the relative mode spacing. A correlation method for the cell-induced spectra is reported and provides a preliminary demonstration that some types of single cells can be differentiated. After further development, the method may provide a useful label-free optical technique for recognizing cells in a microfluidic environment

Fabrication of a Fabry-Pe/spl acute/rot cavity in a microfluidic channel using thermocompressive gold bonding of glass substrates

This paper presents a simple, low-cost, and reliable process for the fabrication of a microfluidic Fabry-Pe/spl acute/rot cavity in a Pyrex glass substrate. The microfluidic channels were etched in HF solution on a glass substrate using a Cr/Au/photoresist etching mask resulting in a channel bottom roughness of 1.309 nm. An effective thermocompressive gold-gold bonding technique was used to bond the photolithographically etched glass substrates inside a 350/spl deg/C oven in a 10/sup -3/ torr vacuum. Pressure was applied to the glass pieces by using two aluminum blocks with intermediate copper sheets. This method takes advantage of using Cr/Au layers both as a wet etching mask and as intermediate bonding layers, requiring only one lithography step for the entire process. The fabrication method is also compatible with the incorporation of dielectric mirror coatings in the channels to form a high-finesse Fabry-Pe/spl acute/rot cavity. A parallelism of 0.095 degrees was measured, and a finesse as high as 30 was obtained using an LED. The microfluidic cavity developed here can be used in electrophoresis and intracavity spectroscopy experiments.

Optofluidic Intracavity Spectroscopy of Canine Hemangiosarcoma

The label-free technique of optofluidic intracavity spectroscopy (OFIS) uses light transmitted through a cellular body in a microfluidic optical resonator to distinguish different types of cells by their optical properties. The OFIS technique has differentiated canine hemangiosarcoma (HSA) cells from monocytes in peripheral blood mononuclear cells based on their distinctive transmission spectra. A single characteristic parameter indicative of strong multi-transverse-mode resonances was determined for each cell by forming a linear combination of the mean and standard deviation of the transmission spectra over one free spectral range, excluding the peaks of passive Fabry-Pérot cavities without cells. The difference in the characteristic parameters of HSA and monocyte samples was statistically highly significant with a p-value as low as 10 6. The same method shows that the characteristic parameters of canine lymphoma and lymphocytes are distinct with p <; 0.005. A receiver operating-characteristic curve constructed from t-distributions fit to the HSA and monocyte data indicates that 95% sensitivity and 98% specificity can be simultaneously achieved.

Optofluidic Intracavity Spectroscopy of Canine Lymphoma and Lymphocytes

Multiple transverse mode, intracavity spectra of canine lymphoma cells in a passive Fabry-Perot cavity are distinct from single-mode spectra of normal lymphocytes. Two-dimensional effective-index modal calculations provide insight into the nuclear size versus refractive index relationship and clarify the impact of lateral optical confinement on modal shift.

Microfluidic cavity surface emitting laser based biosensor

The goal of this research is to characterize different biological cells with the help of intracavity spectroscopy following the work of Gourley et al in 1997. This paper reports initial results on device fabrication, and modulation of laser threshold and slope efficiency, with the bioanalytes refractive index. An approximate mathematical model is also proposed to support the experimental results.

Single cell detection capability of an optofluidic spectroscopic biosensor

Biological cells inside an optofluidic cavity modify the optical cavity modes, providing a probe for optical properties of the cells that can be used to detect and differentiate single cells. Transmission spectra of single biological cells including yeast cells and human blood cells as well as polystyrene spheres in a microfluidic Fabry-Perot cavity fabricated on glass substrates are measured and exhibit cell-type specific features attributed to higher order transverse modes. A method for spectral correlation is also presented to verify the preliminary results of the single cell spectra. The correlation calculation demonstrates that the method is able to differentiate some types of single cells

Microfluidic passive-cavity interferometer-based biosensor

A microfluidic passive cavity interferometer based biosensor was developed in this work. Polystyrene microspheres were used to test the device performance. Measured transmission spectra of single microspheres were compared to the modeled results.

Micro-fluidic passive cavity interferometer based biosensor

A microfluidic passive cavity interferometer based biosensor was developed in this work. Polystyrene microspheres were used to test the device performance. Measured transmission spectra of single microspheres were compared to the modeled results.

Optofluidic intracavity spectroscopy for single cell detection

Spectra of single biological cells including yeast cells and human blood cells using the optofluidic resonant cavity are reported in this work. A method for spectral correlation is also presented to verify the preliminary results of the single cell spectra. The correlation calculation demonstrates that the method is able to differentiate some types of single cells

Intracavity Spectroscopy of Canine Lymphoma Cells in a Microfluidic Channel

Optofluidic intracavity spectroscopy (OFIS) measurements of individual canine lymphoma cells in a microfluidic Fabry-Perot produced repeatable transmission spectra. The transverse mode spacing was more varied for transmission spectra of non-cancerous peripheral blood mononuclear cells