Biomedical subjects

Philippe J Marchand

Publications and source records attributed to Philippe J Marchand.

6 recordsLinked to original sources

PubMed2004

Microfluidic sorting of mammalian cells by optical force switching.

Microfluidic-based devices have allowed miniaturization and increased parallelism of many common functions in biological assays; however, development of a practical technology for microfluidic-based fluorescence-activated cell sorting has proved challenging. Although a variety of different physical on-chip switch mechanisms have been proposed, none has satisfied simultaneously the requirements of high throughput, purity, and recovery of live, unstressed mammalian cells. Here we show that optical forces can be used for the rapid (2-4 ms), active control of cell routing on a microfluidic chip. Optical switch controls reduce the complexity of the chip and simplify connectivity. Using all-optical switching, we have implemented a fluorescence-activated microfluidic cell sorter and evaluated its performance on live, stably transfected HeLa cells expressing a fused histone-green fluorescent protein. Recovered populations were verified to be both viable and unstressed by evaluation of the transcriptional expression of two genes, HSPA6 and FOS, known indicators of cellular stress.

Cell Separation↗

PubMed2004

Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model.

To facilitate quantitation of cellular apoptotic responses to various antineoplastic agents, a laser-based technology, Optophoresis, has been developed to provide analysis of cells without any need for labeling or cell processing. Optophoresis is defined as the analysis of the motion of cells, where the motion is either induced or modified by a moving optical gradient field, which produces radiation pressure forces on the cells in an aqueous suspension. Quantitation of the induced motion provides a basis for distinguishing one population of cells from another. One Optophoretic technique, Fast Scan, measures the distribution of distances traversed by a population of cells when exposed to a fast-moving optical gradient. Fast Scan was validated using a cell-based model of chronic myeloid leukemia treated with Gleevec, a specific inhibitor of aberrant Bcr-Abl protein kinase. The Optophoretic measurements were quantitatively comparable to reference assays with regard to drug selectivity and potency and to target specificity, demonstrating the suitability of this technology for pharmaceutical and clinical applications.

Antineoplastic Agents↗

PubMed2004

Time-of-flight optophoresis analysis of live whole cells in microfluidic channels.

Optophoresis is a non-invasive cell analysis technique that is based on the interaction of live whole cells with optical gradient fields, typically generated by a near-infrared laser. The magnitude of the interaction depends upon the intrinsic physical properties of the cells, such as their refractive index, composition, size, and morphology. Time-of-flight (TOF) optophoresis is an implementation of this technique in a microfluidic environment. It measures cell travel times through a fixed distance with and without irradiation from a laser beam. The magnitude of the optical force from the laser, and therefore the change in transit time introduced by the presence of the infrared laser provides a signature for the cell. By accumulating such measurements for a population of cells (typically 200-300 cells per population), different cell types, drug treatments, or biological states can be compared quantitatively without the need for external labels or markers. An integrated TOF system has been constructed and characterized. The system typically uses square capillaries with 50-100 microm internal diameter and uses a syringe-pump-based flow system that generates initial bulk flow velocities between 200 and 600 microm/sec. Using this TOF technique, we have been able to consistently detect significant differences between normal skin and melanoma cell lines, CCD-1037 and A375, respectively. We have also been able to measure consistent differences in a cell differentiation model (HL60 cell line with DMSO treatment). These early results indicate the potential biological sensitivity of the TOF measurement technique for cellular analysis and cancer diagnostic applications.

Cell Line, Tumor↗

PubMed2003

Optical forces for noninvasive cellular analysis.

A novel, noninvasive measurement technique for quantitative cellular analysis is presented that utilizes the forces generated by an optical beam to evaluate the physical properties of live cells in suspension. In this analysis, a focused, near-infrared laser line with a high cross-sectional intensity gradient is rapidly scanned across a field of cells, and the interaction of those cells with the beam is monitored. The response of each cell to the laser depends on its size, structure, morphology, composition, and surface membrane properties; therefore, with this technique, cell populations of different type, treatment, or biological state can be compared. To demonstrate the utility of this cell analysis platform, we evaluated the early stages of apoptosis induced in the U937 cancer cell line by the drug camptothecin and compared the results with established reference assays. Measurements on our platform show detection of cellular changes earlier than either of the fluorescence-based Annexin V or caspase assays. Because no labeling or additional cell processing is required and because accurate assays can be performed with a small number of cells, this measurement technique may find suitable applications in cell research, medical diagnostics, and drug discovery.

Apoptosis↗

PubMed2002

Misalignment tolerance analysis of free-space optical interconnects via statistical methods.

System-level packaging is one of the critical issues that need to be addressed for free space optical interconnections (FSOI) to become useful in desktop systems. The performance of FSOI, e.g., in terms of system bit-error rate, is greatly affected by misalignments in the optical system. Therefore tolerancing, i.e., the ability to analyze and predict the effects of misalignments in the system, is of prime importance to system designers. We introduce an approach in which we study the effects of optical misalignments and other tolerance factors using statistical methods. We use Monte Carlo simulations, design of the experiments, and regression techniques to fit a polynomial equation that expresses the relationship between the system performance and the tolerance factors. This prediction model can be used for design, cost optimization, and quality control purposes. In addition, we perform a sensitivity analysis to determine those tolerance variables that have the greatest effect on system performance.

Journal Article↗

PubMed2002

Three-dimensional optoelectronic stacked processor by use of free-space optical interconnection and three-dimensional VLSI chip stacks.

We present a demonstration system under the three-dimensional (3D) optoelectronic stacked processor consortium. The processor combines the advantages of optics in global, high-density, high-speed parallel interconnections with the density and computational power of 3D chip stacks. In particular, a compact and scalable optoelectronic switching system with a high bandwidth is designed. The system consists of three silicon chip stacks, each integrated with a single vertical-cavity-surface-emitting-laser-metal-semiconductor-metal detector array and an optical interconnection module. Any input signal at one end stack can be switched through the central crossbar stack to any output channel on the opposite end stack. The crossbar bandwidth is designed to be 256 Gb/s. For the free-space optical interconnection, a novel folded hybrid micro-macro optical system with a concave reflection mirror has been designed. The optics module can provide a high resolution, a large field of view, a high link efficiency, and low optical cross talk. It is also symmetric and modular. Off-the-shelf macro-optical components are used. The concave reflection mirror can significantly improve the image quality and tolerate a large misalignment of the optical components, and it can also compensate for the lateral shift of the chip stacks. Scaling of the macrolens can be used to adjust the interconnection length between the chip stacks or make the system more compact. The components are easy to align, and only passive alignment is required. Optics and electronics are separated until the final assembly step, and the optomechanic module can be removed and replaced. By use of 3D chip stacks, commercially available optical components, and simple passive packaging techniques, it is possible to achieve a high-performance optoelectronic switching system.

Journal Article↗