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. DOI: 10.1103/PhysRevLett.94.196101 PACS numbers: 81.16.Nd, 82.35.Lr, 82.39.Pj Top-down approaches to nanotechnology have the potential to revolutionize biology by making possible the construction of chip-based devices that can not only detect and separate single DNA molecules by size [1-4] but also-it is hoped in the future-actually sequence at the single molecule level [5]. While a number of top-down approaches have been proposed, all these approaches have in common the confinement of DNA to nanometer scales, typically 5-200 nm. Confinement alters the statistical mechanical properties of DNA. A DNA molecule in a nanochannel will extend along the channel axis to a substantial fraction of its full contour length [1,6]. Moreover, confinement is expected to alter the Brownian dynamics of the confined molecule [1]. While the study of confined DNA is interesting from a physics perspective, it is also critical for device design, potentially leading to new applications of nanoconfinement (for example, the use of nanochannels to prestretch and stabilize DNA before threading through a nanopore [5]). Moreover, available models [7][8][9][10][11] and simulations [12,13] are unable to account for the effect of varying confinement over the entire range of scales used in nanodevices. The theory gives asymptotic results valid only in limits that are not necessarily compatible with device requirements [1].Consider a DNA molecule of contour length L, width w, and persistence length P confined to a nanochannel of width D with D less than the radius of gyration of the molecule. When D P, the molecule is free to coil in the nanochannel and the elongation is due entirely to excluded volume interactions between segments of the polymer greatly separated in position along the backbone (see Fig. 1). de Gennes developed a scaling argument for the average extension of a confined self-avoiding polymer [8,12] which was later generalized by Schaefer and Pincus to the case of a persistent self-avoiding polymer [14]. The de Gennes theory predicts an extension r that scales with D in the following way:If the aspect ratio of the channel is not unity, i.e., the width D D 1 does not equal the depth D 2 , then Eq. (1) is still valid provided that D is replaced by the geometric average of the dimensions. As the channel width drops below the persistence length, the physics is dominated not by excluded volume but by the interplay of confinement and intrinsic DNA elasticity. In the strong confinement limit D P, backfolding is energetically unfavorable and contour length is stored exclusively in deflections made by the polymer with the walls. These deflections occur on average over th...

We show the fractionation of whole blood components and isolation of blood plasma with no dilution by using a continuousflow 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 m͞sec and volume rates up to 1 l͞min. 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.

We demonstrate wide-area fabrication of sub-40 nm diameter, 1.5 µm tall, high aspect ratio silicon pillar arrays with straight sidewalls by combining nanoimprint lithography (NIL) and deep reactive ion etching (DRIE). Imprint molds were used to pre-pattern nanopillar positions precisely on a 200 nm square lattice with long range order. The conventional DRIE etching process was modified and optimized with reduced cycle times and gas flows to achieve vertical sidewalls; with such techniques the pillar sidewall roughness can be reduced below 8 nm (peak-to-peak). In some cases, sub-50 nm diameter pillars, 3 µm tall, were fabricated to achieve aspect ratios greater than 60:1.

We report and demonstrate a new method to fabricate single fluidic-channels of uniform channel width (11−50 nm) and over 1.5 cm in length, which are essential to developing innovative bio/chemical sensors but have not been fabricated previously. The method uses unconventional nanofabrication (a combination of crystallographic anisotropic etching, conformal coating, and edge patterning, etc.) to create an imprint mold of a channel pattern and nanoimprint to duplicate such channel. The centimeter-long channel continuity is verified by flowing fluorescent dye-stained water and stretching and transporting DNAs. The 18 by 20 nm channel cross-section was confirmed by measuring the liquid conductance in the channel.One critical challenge in developing many innovative bio/ chemical sensors is the fabrication of a single narrow yet long (centimeter) and continuous fluidic channel at the precisely designated location. 1-7 Such channels of a sub-20 nm width, essential for device function, were hardly fabricated previously because of the intrinsic limitations in the fabrication methods used, particularly the traditional nanofabricationmethods(e.g.,writingandetchingnanostructures). [8][9][10] For example, to explore a new real-time DNA-sequencing device (potentially revolutionary if successful), it requires not only a continuous fluidic channel of a width below 20 nm and a length of a centimeter for stretching and stabilizing DNAs, but also a single channel host for putting electrical or optical sensors inside the channel. 4,5,7,[11][12][13][14][15] Multiple channels will greatly complicate the sensor fabrication and the addressable detection of single DNA. 15,16 These requirements make the fabrication of a single sub-20 nm wide, centimeter-long, continuous fluidic channel extremely challenging due to two main reasons. (a) All scanning nanostructure-writing tools, such as electron beam lithography, ion beam lithography, or scanning probe patterning are limited to a writing field of ∼100 µm for sub-20 nm structures, which is not sufficient for the needed long channel. Stitching of different fields does not have the necessary accuracy to connect two channels into a single continuous channel. All the nanostructure-writing tools based on a fixed writing beam (probe) and a moving stage can barely maintain sub-20 nm writing over centimeter distances. (b) Because of the noise in these writing tools and reactive ion etching (if used), the line-edge-roughness (LER), which has an average size of 5-50 nm, will clog the channel before the average channel width is reduced to 20 nm, because just one large edge variation (far larger than average) can clog the long channel. Interference lithography can make narrow continuous fluidic-channels over centimeter lengths but it usually makes dense, multiple channels rather than a single channel, 15 and it also suffers LER as nanostructure writing tools, preventing a small needed channel width (in principle, a single channel line may be produced by interference lithography under special co...

We present a versatile method for continuous-flow, on-chip biological processing of cells, large bio-particles, and functional beads. Using an asymmetric post array in pressure-driven microfluidic flow, we can move particles of interest across multiple, independent chemical streams, enabling sequential chemical operations. With this method, we demonstrate on-chip cell treatments such as labeling and washing, and bacterial lysis and chromosomal extraction. The washing capabilities of this method are particularly valuable because they allow many analytical or treatment procedures to be cascaded on a single device while still effectively isolating their reagents from cross-contamination.