Bulletin of the American Physical Society
2005 APS March Meeting
Monday–Friday, March 21–25, 2005; Los Angeles, CA
Session J7: Biological Microsystem Technologies Using Microfluidics and Integrated Circuits |
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Sponsoring Units: DBP Chair: Robert M. Westervelt, Harvard University Room: LACC 408B |
Tuesday, March 22, 2005 11:15AM - 11:51AM |
J7.00001: Soft Lithography and Microfluidic Devices Invited Speaker: Complex three dimensional (3D) nanostructures can play important roles in microfluidic devices. High resolution, conformable phase masks provide a means to fabricate, in an experimentally simple manner, classes of 3D nanostructures that are useful for these systems. In this approach, light passing through a phase mask that has features of relief comparable in dimension to the wavelength generates a 3D distribution of intensity that exposes, through a one or two photon process, a photopolymer film throughout its thickness. Developing this polymer yields a structure in the geometry of the intensity distribution, with feature sizes as small as 50 nm. Rigorous coupled wave analysis reveals the fundamental aspects of the optics associated with this method. A broad range 3D nanostructures patterned with it demonstrates its patterning capabilities. Filter elements, passive mixers, separators and optical sensors built inside microfluidic channels represent examples of the many types of devices that can be constructed. [Preview Abstract] |
Tuesday, March 22, 2005 11:51AM - 12:27PM |
J7.00002: Programmed Adsorption and Release of Proteins in a Microfluidic Device Invited Speaker: Microfluidic devices are under development for the preconcentration, separation, sensing, and analysis of proteins from small solution volumes (ultimately the contents of single cells). As system dimensions continue to shrink, interfacial interactions become more and more important in dictating device performance. Research is in progress to develop self-assembled monolayers (SAMS) that can be programmed using ``on-chip'' stimuli including heat, light, and electric fields to manipulate interfacial interactions including electrical double layer forces, hydrations forces, and hydrophilic/hydrophobic interactions within confined microchannel environments. While several examples of such SAMS will be provided, the focus of this talk will be on thermally-activated thin films of the polymer poly(n-isopropylacrylamide)(PNIPAM) that can be used for the reversible trapping of proteins. At room temperature, measurements obtained using the interfacial force microscope (IFM) show that PNIPAM films swell to generate a repulsive hydration force that inhibits protein adsorption. Above a transition temperature of 35$^{\circ}$C, the ordered water within PNIPAM ``melts,'' allowing proteins to come into contact with the substrate and form an adsorbed protein monolayer. PNIPAM films have been integrated into a microhotplate device that allows the adsorption and desorption of proteins to be switched in a controlled fashion. Results obtained using ellipsometry and the quartz crystal microbalance show that the resulting reversible protein trap can be used for protein preconcentrations, crude protein separations, and (in conjunction with antibody trapping) highly selective systems for trapping and releasing specific antigens. [Preview Abstract] |
Tuesday, March 22, 2005 12:27PM - 1:03PM |
J7.00003: Hybrid IC / Microfluidic Chips for the Manipulation of Biological Cells Invited Speaker: A hybrid IC / Microfluidic chip that can manipulate individual biological cells in a fluid with microscopic resolution has been demonstrated. The chip starts with a custom-designed silicon integrated circuit (IC) produced in a foundry using standard processing techniques. A microfluidic chamber is then fabricated on top of the IC to provide a biocompatible environment. The motion of biological cells in the chamber is controlled using a two-dimensional array of micro-scale electromagnets in the IC that generate spatially patterned magnetic fields. A local peak in the magnetic field amplitude will trap a magnetic bead and an attached cell; by moving the peak's location, the bead-bound cell can be moved to any position on the chip surface above the array. By generating multiple peaks, many cells can be moved independently along separate paths, allowing many different manipulations of individual cells. The hybrid IC / Microfluidic chip can be used, for example, to sort cells or to assemble tissue on micrometer length scales. To prove the concept, an IC / Microfluidic chip was fabricated, based on a custom-designed IC that contained a two-dimensional microcoil array with integrated current sources and control circuits. The chip was tested by trapping and moving biological cells tagged with magnetic beads inside the microfluidic chamber over the array. By combining the power of silicon technology with the biocompatibility of microfluidics, IC / Microfluidic chips will make new types of investigations possible in biological and biomedical studies. [Preview Abstract] |
Tuesday, March 22, 2005 1:03PM - 1:39PM |
J7.00004: Biotechnology Research at Intel Invited Speaker: The Intel biotechnology research program is sponsored by Intel Research of Intel Corporation, aimed at developing novel detection technologies for ultra-sensitive analysis of biomolecules. Towards this goal, we have developed techniques that can be used to isolate and manipulate individual DNA molecules, as well as to place molecules in desired positions in a microfluidic system for effective detection. We have also developed a Raman spectroscopy system together with novel colloidal chemistries that allow single molecule detection of nucleotides and protein bioanalytes. We view this internal research effort as a long-term opportunity. We hope our gained expertise in the biotechnology area will allow us to develop tools that can be used to diagnose diseases and select the best treatments at early disease stages. [Preview Abstract] |
Tuesday, March 22, 2005 1:39PM - 2:15PM |
J7.00005: Biomagnetics and Cell-Based Biochips Invited Speaker: This presentation will review various micro- and nanotechnologies that we have developed over the past decade in our efforts to manipulate and probe living cells. In early studies, we used magnetic micro-particles to apply controlled mechanical forces to surface membrane receptors. We did this to probe cellular mechanical properties, and to investigate the molecular basis of mechanotransduction -- how mechanical forces are transduced into changes in intracellular biochemistry. The magnetic beads were coated with ligands for adhesion receptors, such as synthetic RGD (arginine-glycine-aspartate) peptides or antibodies that bind to membrane integrin receptors. Controlled twisting (torque) or pulling (tension) forces were exerted on the integrin-bound beads using magnetic twisting or pulling cytometry. To investigate the cellular response to dynamic forces, and to increase the level of stress applied, an electromagnetic needle was developed to apply a temporally varying magnetic field controlled by a user-defined solenoidal current; the end of the needle also was electropolished to produce a nanoscale pole tip. Magnetic forces applied to integrin receptors, but not other cell-surface receptors, induced force-dependent recruitment of cytoskeletal linker (focal adhesion) proteins to the site of bead binding, resulting in assembly and mechanical strengthening of the adhesions. Stress application to integrins also resulted in force-dependent increases in cAMP signaling and induction of gene transcription. These experiments revealed that integrins and the cytoskeleton play a central role in cellular mechanotransduction.studies in collaboration with George Whitesides (Harvard U.), we used microcontact printing techniques with self- assembled monolayers of alkanethiols to microfabricate extracellular matrix-coated adhesive islands of defined size, shape, and position on the micrometer scale. When cells were plated on these islands, the spread to take on the form of the island. These studies revealed that cells can be switched between growth, differentiation, and death (apoptosis) by varying the degree to which a cell physically can distend. When cells grown on islands with corners (e.g., squares, triangles) were stimulated with motility factors, the cells preferentially extended new motile processes from the corner regions, whereas cells on circular islands showed no bias. These findings demonstrated that much of cell behavior is controlled through physical interactions between cells and their adhesive substrate, and that microfabrication methods may be useful for tissue engineering, as well as creation of ``laboratories on a chip'' or biosensor devices that incorporate living mammalian cells. addition, in experiments with Bob Westervelt and Donhee Ham (Harvard U.), we have demonstrated the feasilibility of using microelectromagnetic circuits and CMOS technology to physically pull cells out from medium magnetically, and to move them in a directed manner. This approach may have great value for cell separation applications. Finally, with Whitesides group, we also demonstrated that microfluidics technologies may be used to deliver chemicals or probes to different regions of the same living cell under flow conditions. This provides a novel way to create chemical gradients at the subcellular scale and thereby probe the relation between cell structure and function. We also are currently exploring novel uses of microfluidics technologies, including their application for clinical cell separation applications. Taken together, this body of his work clearly demonstrates the great value of microsystem and microfluidic approaches for the analysis and manipulation of living cells. These approaches may have great value, both for fundamental scientific research and for clinical applications. [Preview Abstract] |
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