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Biomedical subjects

Stephen Y Chou

Publications and source records attributed to Stephen Y Chou.

8 recordsLinked to original sources

Deterministic hydrodynamics: taking blood apart.

We show the fractionation of whole blood components and isolation of blood plasma with no dilution by using a continuous-flow deterministic array that separates blood components by their hydrodynamic size, independent of their mass. We use the technology we developed of deterministic arrays which separate white blood cells, red blood cells, and platelets from blood plasma at flow velocities of 1,000 microm/sec and volume rates up to 1 microl/min. We verified by flow cytometry that an array using focused injection removed 100% of the lymphocytes and monocytes from the main red blood cell and platelet stream. Using a second design, we demonstrated the separation of blood plasma from the blood cells (white, red, and platelets) with virtually no dilution of the plasma and no cellular contamination of the plasma.

Blood Platelets↗

Sub-20-nm alignment in nanoimprint lithography using Moiré fringe.

Accurate multi-level overlay capability for nanoimprint lithography (NIL) is essential to integrated circuit manufacturing and other multilayer imprint applications. Using the "beat" grating image (Moiré fringe) generated by overlaying two sets of gratings that have slightly different periods, we obtained an alignment signal with a sensitivity better than 10 nm in nanoimprint lithography. The alignment signal is, as expected, independent of the size of the gap between the wafer and the imprint mold. We achieved a single-point overlay accuracy (error distribution) of sub-20 nm between the first and second imprinted layers by using two sets of Moiré fringes. With higher precision nanopositioning stages, better single-point alignment accuracy is expected. Furthermore, we achieved sub-150 nm alignment over an area of 1 sq in and sub-250 nm over the entire area of a 4 in wafer using simple low-resolution stages without temperature control or wafer-mold mismatch compensation. With better stages, precision temperature control, and wafer-mold mismatch compensation, we believe that much higher overlay alignment accuracy over large areas (either in a 1 sq in die or a full wafer) is feasible.

Moire Topography↗

Air cushion press for excellent uniformity, high yield, and fast nanoimprint across a 100 mm field.

Imprint pressure uniformity is crucial to the pattern uniformity and yield of nanoimprint lithography (NIL) and, hence, its applications. We studied a novel imprint method, air cushion press (ACP), in which the mold and substrate are pressed against each other by gas pressure rather than solid plates, and compared it with a common method, solid parallel-plate press (SPP). We found that (a) under normal imprinting conditions the measured pressure distribution across a 100-mm-diameter single imprint field in ACP is nearly an order of magnitude more uniform; (b) ACP is immune to any dust and topology variations on the backside of the mold or substrate; (c) when a dust particle is between the mold and substrate, ACP reduces the damage area by orders of magnitude; (d) ACP causes much less mold damage because of significantly less lateral shift between the mold and substrate; and (e) ACP has much smaller thermal mass and therefore significantly faster speed for thermal imprinting.

Air Pressure↗

Statics and dynamics of single DNA molecules confined in nanochannels.

The successful design of nanofluidic devices for the manipulation of biopolymers requires an understanding of how the predictions of soft condensed matter physics scale with device dimensions. Here we present measurements of DNA extended in nanochannels and show that below a critical width roughly twice the persistence length there is a crossover in the polymer physics.

Bacteriophage lambda↗

Electrostatic force-assisted nanoimprint lithography (EFAN).

We present and demonstrate a novel imprint method, electrostatic force-assisted nanoimprint lithography (EFAN), where a voltage applied between a mold and a substrate generates an electrostatic force that presses the mold into a resist on the substrate. We have successfully used EFAN to pattern nanostructures in a photocurable resist spin-coated on a wafer, with high fidelity and excellent uniformity over the entire substrate, in ambient atmosphere without using a vacuum chamber. In initial tests without any process optimization, 100 nm half-pitch gratings with a residual layer thickness of 22+/-5 nm were imprinted across a 100 mm diameter wafer in about 2 s. Furthermore, numerical calculations show that the field magnitude experienced by the dielectric layers on the substrate is much less than their breakdown limit. Hence, EFAN is well suited for step-and-repeat nanoimprint lithography, and its simple operation can simplify and speed up multilayer alignment process.

Crystallization↗

Cylindrically symmetric electrohydrodynamic patterning.

Cylindrically symmetric structures such as concentric rings and rosettes arise out of thin polymeric films subjected to strong electric fields. Experiments that formed concentric rings and theory capable of explaining these and other cylindrical structures are presented. These rings represent an additional member of a class of structures, including pillars and holes, formed by electrohydrodynamic patterning of thin films, occasionally referred to as lithographically induced self-assembly. Fabrication of a set of concentric rings begins by spin coating a thin poly(methyl methacrylate) film onto a silicon wafer. A mask is superimposed parallel to the film leaving a similarly thin air gap. Electric fields, acting in opposition to surface tension, destabilize the free interface when raised above the glass transition temperature. Central pillars nucleate under small cylindrical protrusions patterned on the mask. Rings then emerge sequentially, with larger systems having as many as 10 fully formed rings. Ring-to-ring spacings and annular widths, typically on the order of a micron, are approximately constant within a concentric cluster. The formation rate is proportional to the viscosity and, consequently, has the expected Williams-Landel-Ferry dependence on temperature. In light of these developments we have undertaken a linear stability analysis in cylindrical coordinates to describe these rings and ringlike structures. The salient feature of this analysis is the use of perturbations that incorporate their radial dependence in terms of Bessel functions as opposed to the traditional sinusoids of Cartesian coordinates. The theory predicts approximately constant ring-to-ring spacings, constant annular widths, and growth rates that agree with experiment. A secondary instability is observed at higher temperatures, which causes the rings to segment into arcs or pillar arrays. The cylindrical theory may be generalized to describe hexagonal pillar/hole packing, gratings, and rosettes with the first being of particular importance given the ubiquitous observation of hexagonal packing. The perturbation analysis presented here is relevant to any system with cylindrical symmetry, for which the radial dependence can be described in terms of Bessel functions.

Journal Article↗

Micro- and nanofluidics for DNA analysis.

Miniaturization to the micrometer and nanometer scale opens up the possibility to probe biology on a length scale where fundamental biological processes take place, such as the epigenetic and genetic control of single cells. To study single cells the necessary devices need to be integrated on a single chip; and, to access the relevant length scales, the devices need to be designed with feature sizes of a few nanometers up to several micrometers. We will give a few examples from the literature and from our own research in the field of miniaturized chip-based devices for DNA analysis, including dielectrophoresis for purification of DNA, artificial gel structures for rapid DNA separation, and nanofluidic channels for direct visualization of single DNA molecules.

Cell Separation↗

Ultrafast and direct imprint of nanostructures in silicon.

The fabrication of micrometre- and nanometre-scale devices in silicon typically involves lithography and etching. These processes are costly and tend to be either limited in their resolution or slow in their throughput. Recent work has demonstrated the possibility of patterning substrates on the nanometre scale by 'imprinting' or directed self-assembly, although an etching step is still required to generate the final structures. We have devised and here demonstrate a rapid technique for patterning nanostructures in silicon that does not require etching. In our technique which -- we call 'laser-assisted direct imprint' (LADI) -- a single excimer laser pulse melts a thin surface layer of silicon, and a mould is embossed into the resulting liquid layer. A variety of structures with resolution better than 10 nm have been imprinted into silicon using LADI, and the embossing time is less than 250 ns. The high resolution and speed of LADI, which we attribute to molten silicon's low viscosity (one-third that of water), could open up a variety of applications and be extended to other materials and processing techniques.

Journal Article↗