MXPA06003201A - Photocurable perfluoropolyethers for use as novel materials in microfluidic devices - Google Patents

Abstract

A functionalized photocurable perfluoropolyether is used as a material for fabricating a solvent-resitant microfluidic device. Such solvent- resistant microfluidic devices can be used to control the flow of small amounts of a fluid, such as an organic solvent, and to perform microscale chemical reactions that are not amenable to other polymer-based microfluidic devices.

Description

PERFLUOUS PHOTOCUSABLE OPOLIETERS FOR USE IN MATERIALS NOVEDOSOS IN MICROFLUIDIC DEVICES GOVERNMENT INTERESTS A part of this invention was made with support from the Office of Naval Search Grant No. N00014-0201-0185 of the United States Government. The government of the United States has certain rights to a part of the investigation. FIELD OF THE INVENTION The use of a photocurable perfluoropolyether material (PFPE) to manufacture a microfluidic device based on solvent-resistant PFPE, methods for flowing a material and effecting a chemical reaction in a microfluidic device based on solvent-resistant PFPE, and microfluidic device based on solvent-resistant PFPE itself. ABBREVIATIONS aL Atoliters ° C degrees Celsius cm centimeters cSt centistoke DBTDA dimethyl tin diacetate DMA dimethacrylate DMPA 2, 2-toxi-2-phenylacetophenone DMTA thermal, mechanical and dynamic analysis REF: 171535 EIM = 22-isocyanoethyl methacrylate fL = Femtolitros Freon 113 = 1, 1,2-trichlorotrifluoroethane g = grams h = hours Hz = Hertz kHz = kilohertz kPa = kilopascals MHz = megahertz min = minutes mL = milliliters mm = millimoles millimeters = millimoles mN = milli-Newtons pf = melting point nL = nanoliters nm = nanometers PDMS = polydimethylsiloxane PFPE = perfluoropolyether PL = picolitres psi = pounds per square inch s seconds Tv = vitreous transition temperature μL = microlitres μm = micrometers UV = ultraviolet = watts ZDOL = poly (oxide) of tetrafluoroethylene-difluoromethylene co-oxide) a ,? diol BACKGROUND OF THE INVENTION The microfluidic devices developed in the early 1990s were made of hard materials, such as silicon glass, using photolithography and etching techniques. See Ouellette, J., The Industrial Physicist 2003, August / September, 14-17; Scherer, A., et al., Science 2000, 290, 1536-1539. The photolithography and engraving techniques, however, are expensive and labor-intensive and require clean room conditions and have several disadvantages from the point of view of the materials. For these reasons, soft materials have emerged, alternative materials for the manufacture of microfluidic devices. The use of soft materials has made it possible to manufacture and operate devices that contain valves, pumps and mixers. See, for example, Ouellette, J., The Industrial Physicist 2003, August / September, 14-17; Scherer, A., et al., Science 2000, 290, 1536-1539; Unger, M.A., et al., Science 2000, 288, 113-116; McDonald, J. C, et al. , Acc. Chem. Res. 2002, 35, 491-499; and Thorsen, T., et al. , Science 2002, 298, 580-584. For example, one of those microfluidic devices allows control over the reflux direction are the use of mechanical valves. See Zhao. B., et al. , Science 2001, 291, 1023-1026. The increasing complexity of microfluidic devices has created a demand for the use of these devices in a rapidly growing number of applications. Until now, the use of soft materials has allowed microfluidic devices to develop into a useful technology that has found application in the genomic map tracing, fast separations, detectors, reactions at the nanometric scale and pressure by inkjet, distribution of drugs , laboratories on an integrated microcircuit, in vitro diagnostics, injection nozzle, biological studies, and separation or selection of drugs. See, for example, Ouellette, J., The Industrial Physicist 2003, August / September, 14-17; Scherer, A., et al., Science 2000, 290, 1536-1539; Unger, M.A., et al. , Science 2000, 288, 113-116; McDonald, J. C, et al., Acc. Chem. Res. 2002, 35, 491-499; Thorsen T., et al., Science 2002, 298, 580-584; and Liu, J., et al. , Anal. Chem. 2003, 75, 4718-4723. Poly (dimethylsiloxane) (PDMS) is the soft material of choice for many applications of microfluidic arrangements. See Scherer, A., et al., Science 2000, 290, 1536-1539; Unger, M.A., et al., Science 2000, 288, 113-116; McDonald, J. C, et al., Acc. Chem. Res. 2002, 35, 491-499; Thorsen, T., et al-, Science 2002, 298, 580-584; and Liu, J., et al. , Anal. Chem. 2003, 75, 4718-4723. A PDMS material offers numerous attractive properties in microfluidic applications. After crosslinking, the PDMS becomes an elastomeric material with a low Young's modulus, for example, of approximately 750 kPs. See Unger, M.A., et al. , Science 2000, 288, 113-116. This property allows the PDMS to conform to surfaces and form reversible. In addition, the PDMS has a low surface energy, for example, of approximately 20 erg / cm2, which can facilitate its release from molds after its formation, See Scherer. A., et al., Science 2000, 290, 1536-1539; McDonald, J. C, et al. , Acc; Chem. Res. 2002, 35, 491-499. Another important characteristic of the PDMS is its outstanding gas permeability. This allows gas bubbles within the channels of the microfluidic device to leak out of the device. This property is also useful for supporting cells and microorganisms within the characteristics of the microfluidic device. The non-toxic nature of silicones, such as PDMS, is also beneficial in this respect and allows opportunities in the field of medical implants. McDonald, J.C., et al., Acc. Chem. Res. 2002, 35, 491-499. Many current PDMS microfilm devices are based on Sylgard® 184 (Dow Corning, Midland, Michigan, United States of America). Sylgard® 184 is thermally cured through a platinum catalyzed hydrosilation reaction. The complete curing of the Sylgard® 184 can take up to 5 hours. The synthesis of a photocurable PDMS material has recently been reported, however, with mechanical properties similar to those of Sylgard® 184 for use in lithography. See Choi, K.M., et al., J. Am. Chem. Soc. 2003, 125, 4060-4061. Despite the above mentioned advantage, PDMS suffers from a disadvantage in microfluidic applications, since it swells in most organic solvents. Thus, PDMS-based microfluidic devices have a limited capacity with several organic solvents. See Lee, J. N., et al., Anal. Chem. 2003, 75, 6544-6554. Among those organic solvents that swell to PDMS are hexanes, ethyl ether, toluene, dichloromethane, acetone, and acetonitrile. See Lee, J. N., et al., Anal. Chem. 2003, 5, 6544-6554. The swelling of a PDMS microfluidic device by organic solvents can disturb its characteristics on a micrometric scale, for example, a channel or a plurality of channels and can restrict or completely interrupt the flow of organic solvents through the channels. In this way, microfluidic applications with a PDMS-based device are limited to the use of fluids, such as water that do not swell to PDMS. As a result, applications that require the use of organic solvents will probably need to use microfluidic systems made of hard materials, such as glass and silicon, see Lee. J. N., et al., Anal. Chem. 2003.75, 6544-6554. This method, however, is limited by the disadvantage of manufacturing microfluidic devices of hard materials. In addition, devices and materials based on PDMS are notorious for not being adequately inert enough to allow them to be used even in aqueous chemical methods. For example, PDMS is susceptible to react with weak and strong acids and bases. PDMS-based devices are also notorious for containing extractable elements, particularly extractable oligomers and cyclic siloxanes, especially after exposure to acids and bases. Because the PDMS is easily swollen by organic, hydrophobic materials, even those hydrophobic materials that are slightly soluble in water can be partitioned into the PDMS-based materials used to build microfilm-based PDMS devices. In this way, an elastomeric material that exhibits the attractive mechanical properties of PDMS combined with a resistance to swelling of common organic solvents would extend the use of microfluidic devices to a variety of new chemical applications that are accessible by current PDMS-based devices. Accordingly, the method demonstrated by the subject matter described herein uses an elastomeric material, more particularly a photocurable perfluoropolyether material (PFPE), which is resistant to swelling in common organic solvents to manufacture a microfluidic device. The photocurable PFPE materials represent a unique class of fluoropolymers that are liquid at room temperature, exhibit low surface energy, low modulus, high gas permeability, and low toxicity with the additional feature that they are extremely chemically resistant. See Scheirs. J., Modern Fluoropolymers; John Wiley & Sons, Ltd.: New York, 1997; pp 435-485. In addition, the PFPE materials exhibit hydrophobic and lipophobic properties. For this reason, PFPE materials are often used as lubricants over high performance machinery that operates in harsh conditions. The synthesis and solubility of PFPE materials in carbon dioxide has been reported. See Bunyard, W., et al., Macromolecules 1999, 32, 8224-8226. The subject matter disclosed herein describes the use of a photocurable perfluoropolyether as a material for manufacturing a solvent-resistant microfluidic device. The use of a photocurable perfluoropolyether as a material for manufacturing a microfluidic device solves the problems associated with swelling in organic solvents exhibited by microfluidic devices made of other polymeric materials, such as PDMS. Accordingly, microfilm devices based on PFPE can be used to show the flow of a small volume of fluid, such as an organic solvent, and to perform chemical reactions on a microscopic scale that have not been sensitive to other polymeric microfluidic devices. • SUMMARY OF THE INVENTION The subject material disclosed herein discloses the use of a photocurable PFPE material to manufacture a solvent-resistant microfluidic device. More particularly, in some embodiments, the subject matter disclosed herein discloses a method for forming a structured layer of a light-cured PFPE material. In some embodiments, the method comprises coating a substrate, such as an etched silicon plate, with a perfluoropolyether precursor and photocuring the perfluoropolyether precursor to form a structure layer of a light-cured perfluoropolyether. In some embodiments, the subject matter disclosed herein discloses a method for forming a light-cured, multi-layered perfluoropolyether material. In some embodiments, the method comprises superimposing a structured layer of the light-cured perfluoropolyether on a second layer of the light-cured perfluoropolyether, wherein the patterns of the first and second layer of the light-cured perfluoropolyether are aligned in a predetermined alignment, and then exposing the first and second layers. of the photocured perfluoropolyether to ultraviolet radiation over a period of time. This curing step causes the two layers to adhere to each other, thereby creating a seal between the two structured layers of the light-cured perfluoropolyether. In some embodiments, the multi-layer structured perfluoropolyether structure comprises a plurality of channels on a microscopic scale, which may further comprise an integrated network of channels on a microscopic scale. Accordingly, in some embodiments, the subject matter disclosed herein describes a method of tracking a material through a network of channels integrated on a microscopic scale. In some embodiments, the method of flowing a material comprises actuating a valve structure within the channels at a microscopic scale. In some embodiments, the method of flowing a material comprises a laterally actuated valve structure. In some embodiments, the method of flowing a material comprises flow channels of different shapes and dimensions. In some dimensions, the method of flowing a material comprises operating multiple valve structures simultaneously to control the flow through a multiplexed network of channels on a microscopic scale. In some embodiments, the subject matter disclosed herein describes a method for effecting a chemical reaction in a microfluidic device, wherein the method comprises contacting a first reagent and a second reagent in the microfluidic device to form a reaction product. In some embodiments, the first reagent and the second reagent are independently selected from one of a nucleotide and a polynucleotide, wherein the reaction product comprises a polynucleotide. In some embodiments, the polynucleotide is DNA. In some embodiments the subject matter disclosed herein discloses a method for incorporating a microfluidic device by an integrated reaction with flow system. In addition, in some embodiments, the subject matter disclosed herein describes a method for selecting a sample by a characteristic. In some embodiments, the subject matter covered by the present describes a method for distributing a material. In some embodiments, the subject material disclosed herein describes a method for separating a material. Certain objectives of the subject matter disclosed herein have already been established above, which are resolved in whole or in part by the subject matter disclosed herein, other aspects and objectives will become apparent as the description proceeds when take in conjunction with the accompanying drawings and examples as best described here below. BRIEF DESCRIPTION OF THE FIGURES FIGS. 1A-1C are a series of schematic views from one end that describe the formation of a structured layer according to the subject matter disclosed herein. Figures 2A-2D are a series of schematic views -from one end-which describes the formation of a microfluidic device comprising two layer structures according to the subject matter disclosed herein. Figure 3A is a cross-sectional view of a microfilm device based on PFPE having an open flow channel. Figure 3B is a cross-sectional view of a microfilm device based on PFPE showing a substantially closed flow channel. Figure 4A is a cross-sectional view of a rectangular flow channel. Figure 4B is a cross-sectional view of a flow channel having a curved upper surface. Figure 5A is a plan view illustrating a valve structure operated laterally in an open position. Figure 5B is a plan view illustrating a valve structure operated laterally in a closed position. Figure 6A is a schematic top view of a control channel that drives multiple flow channels simultaneously. Figure 6B is an elevation view, in section, along the control channel 322 as shown in Figure 6A. Figure 7 is a schematic illustration of a multiplexed system adapted to allow flow through several channels. Figure 8 is a schematic plan view of a microfluidic device according to the subject matter disclosed herein. Figure 9 is a schematic of an integrated microfluidic system for the synthesis of biopolymers. Figure 10 is a schematic view of a system for flowing a solution or conducting a chemical reaction in a microfluidic device according to the subject matter disclosed herein. The microfluidic device 800 is described as a schematic view as shown in Figure 8.

Figure 11 is a graph of viscosity versus shear rate for Sylgard® 184 and perfluoropolyether dimethacrylate materials (PFPE DMA). Figure 12 depicts thermal dynamic mechanical analysis (DMTA) of traces of crosslinked polydimethylsiloxane (PDMS) and perfluoropolyether (PFPE) materials showing the maximum in the loss modulus as a function of temperature. Figures 13A-13C describe a method of manufacturing the representative device. Fig. 13A: A partially separates a thin layer (20 μm) and a thick layer (5 mm) of PFPE DMA. Fig. 3B: The thick layer is detached from its plate, rotated 90 ° and placed on top of the thin layer. The entire device is then fully cured to adhere to the two layers together. Fig. 13C: The device is detached from the plate. Figure 14 depicts a photograph of a dye solution of dichloromethane, acetonitrile, and methanol entering a PFPE device channel (left). In comparison, I did not get a solution to the PDMS channel of the same size due to the swelling (right). Figures 15A-15C describe a photograph illustrating the actuation of a valve. Fig. 15A: top-down view of the channels that do not contain solvent. The channels of the layer (fluid) run vertically, while those on the thick layer (air) run horizontally. Fig. 15B: The thin layer channel filled with a stained solution of acetonitrile, dichloromethane, and methanol. Fig. 15C: Actuation of the valve produced by the introduction of 25 psi of air into the channel of the thick layer. A schematic representation of the valve is presented below each image. DETAILED DESCRIPTION OF THE INVENTION Now the subject matter disclosed herein will now be described in greater detail with reference to the accompanying drawings and the examples, in which representative embodiments are shown. The subject matter disclosed herein can, however, be realized in different forms and the limitations in the modalities set forth herein should not be constituted. Instead, those modalities were provided so that this description is complete and complete, and will fully extend the scope of those modalities to those skilled in the art. Unless otherwise decided, the technical and scientific terms written herein have the same meanings that are commonly understood by one of ordinary skill in the art to which the subject matter disclosed herein belongs. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety.

Throughout the specification and claims, a given chemical formula or name will encompass all optical isomers and stereoisomers, as well as racemic mixtures where those isomers and mixtures exist. 1. Definitions As used herein the term "microfluidic device" generally refers to a device through which materials, particularly fluid-containing materials, such as liquids, in some embodiments on a microscopic scale and some nanoscale modalities can be transported. Thus, the microfluidic devices described by the subject matter disclosed herein may comprise features on a microscopic scale, nanoscale, and combinations thereof. Accordingly, a microfluidic device typically comprises structural or functional features sized in the order of a millimeter scale or less, which are capable of handling a fluid at a flow rate of the order of one microliter / min or less. Typically, these features include but are not limited to channels, fluid reservoirs, reaction chambers, mixing chambers, separation regions. In some examples, the channels include at least one cross section dimension that is in the range of about 0.1 μm to about 500 μm. The use of dimensions of this order allows the incorporation of a greater number of channels in a smaller area, and uses smaller volumes of fluids. A microfluidic device may exist alone or may be part of a microfluidic system which, for example, and without limitation, may include: pumps for introducing fluids, eg, samples, reagents, buffers and the like the system and / or through the system; equipment or detection systems; Data storage systems; and control systems for controlling the transport and / or direction of fluids within the device, verifying and controlling environmental conditions to which the fluids in the device are subjected, for example, temperature, current and the like. As used herein, the terms "channel", "microscopic scale channel" and "microfluidic channel" are used interchangeably and can mean a recess or cavity formed with a material imparting a pattern from a structured substrate in a material or by any material removal technique or may mean a recess or cavity in combination with any suitable fluid conducting structure mounted in the recess or cavity, such as a capillary tube or the like. As used herein the terms "flow channel" and "control channel" are used interchangeably and can mean a channel in a microfluidic device in which a material, such as a fluid, for example, a gas or a liquid, can flow through it. More particularly, the term "flow channel" refers to a channel in which a material of interest, for example, a solvent or a chemical reagent, can flow therethrough. Further, the term "control channel" refers to a flow channel in which a material, such as a fluid, for example a gas or a liquid, can flow through it in such a way as to drive a valve or pump. As used herein, the term "valve" unless otherwise indicated refers to a configuration in which two channels are separated by an elastomeric segment, for example, a segment of PFPE, which can be bent towards or retract from one. of the channels, for example, a flow channel, in response to a driving force applied to the other channel, for example, a control channel. As used herein the term "pattern" can mean a channel or a microfluidic channel or an iptegrada network of microfluidic channels which, in some embodiments, can be intercepted at predetermined points. A pattern may also comprise one or more of a fluid reservoir on a microscopic scale, a reaction chamber on a microscopic scale, a mixing chamber on a microscopic scale and a separation region on a microscopic scale.

As used here, the term "intercept" can mean joining at a point, meeting at a point, cutting through or crossing, or meeting at a point and interposing. More particularly, as used herein, the term "intercept" describes a mode where two channels meet at a point, meet at a point and intersect or intersect each other. As a result, in some modalities they can intercept, that is, meet at a point or meet at a point and cut themselves through each other, and be in microfluidic communication with each other. In some modalities, two channels can be intercepted, that is, meet at a point superimposed on each other and not be in fluid communication with each other, as is the case of a flow channel and a control channel being intercepted. As the term "communicates" is used here (for example, a first component "communicates with" or "is in communication with" a second component) and grammatical variations thereof are used to indicate a structural, functional, mechanical, electrical, optical or fluidic, or any combination thereof, between two or more components or elements. Therefore, the fact that it is said which components are communicated with a second component is not intended to exclude the possibility of being present, additional components between and / or associated or operatively coupled, with the first and second components.

With reference to the use of a microfluidic device to manage the containment or movement of the fluid, the terms "in", "order", "to", "to", "through" and "cross" the device usually has equivalent meanings. As used herein, the term "monolithic" refers to a structure that comprises or acts as a single uniform structure. As used herein, the term "non-biological organic materials" refers to organic materials, that is, those compounds that have covalent carbon-carbon bonds, other than biological materials. As used herein the term "biological materials" includes polymers of nucleic acid (eg, DNA, RNA) amino acid polymers (eg, enzymes) and small organic compounds (eg, steroids, hormones) where small organic compounds have biological activity, especially biological activity for commercially significant humans or animals, such as pets and farm livestock, and where small organic compounds are used primarily for therapeutic or diagnostic purposes. Although biological materials are of interest with respect to pharmaceutical and biotechnological applications, a large number of applications involve chemical processes that are better than other biological materials, that is, non-biological organic materials. Following the conversions of the current patent laws, the terms "a", "one" and "the" refer to "one or more" when used in this application, including the claims. Thus, for example, the reference "a microfluidic channel" includes a plurality of those microfluidic channels and so on. II Method for Making a Microfluidic Device from Perfluoropolyether Material Photocurable The subject matter disclosed herein describes a method for manufacturing a microfluidic device from a photocurable perfluoropolyether material (PFPE). More particularly, the subject matter disclosed herein discloses a method for forming a structured layer of a photocurable PFPE material. Also described is a microfluidic device comprising at least one structured layer of photocurable PEPE material. II.A. Method for Forming a Structural Layer of a Photocurable Perfluoropolyether Material Material. In some embodiments, the subject matter disclosed herein provides a method for forming a structured layer of a photocurable PFPE material. Referring now to Figures 1A-1C, a schematic representation of one embodiment of the subject matter disclosed herein is shown. A substrate S having a structured surface PS comprising a relief projection P is described. Accordingly, the structured surface PS of a substrate S comprises at least one relief projection P which conforms to the pattern. In some embodiments, the structured surface PS of the substrate S comprises a plurality of raised projections P which form a complex pattern. As best seen in Figure IB, a polymeric precursor PP is placed on the structured surface PS of the substrate S. The polymeric precursor PP can comprise a perfluoropolyether. As shown in Figure IB, UV ultraviolet use is applied to provide the photocuring of the PP polymer precursor. After curing the polymeric precursor PP, a structured layer PL of a light-cured perfluoropolyether is formed as shown in Figure 1C. As shown in Figure 1C, the structured layer PL of the light-cured perfluoropolyether comprises a cavity R which forms in the lower surface of the structured layer PL. The dimensions of the cavity R correspond to the dimensions of the relief projection of the structured surface PS of the substrate S. In some embodiments, the cavity R comprises at least one CH channel, which in some embodiments of the subject matter revealed by the present comprises a channel on a microscopic scale. The structured layer PL is removed from the PS structural surfaces of the substrate S for the microfluidic device MD. Accordingly, in some embodiments, a method for forming a structured layer of a light-cured perfluoropolyether comprises: (a) providing a substrate, wherein the substrate comprises a structured surface; (b) contacting a perfluoropolyether precursor with the structured surface of the substrate. (c) photocuring the perfluoropolyether precursor to form a structured layer of a light-cured perfluoropolyether. In some embodiments, a method for forming a structured layer of a light-cured perfluoropolyether comprises: a) coating the structural surface of a substrate with a mixture of a perfluoropolyether precursor and a photo initiator to form a structured coated substrate; (b) exposing the coated, structured substrate to ultraviolet radiation for a period of time to form a layer of a light-cured perfluoropolyether on the structured substrate; (c) removing the light-cured perfluoropolyether layer from the structured substrate to produce a structured layer of the light-cured perfluoropolyether.

In some embodiments, the structured substrate comprises a layer of engraved silicon. In some embodiments, the structured substrate comprises a structured photoresist substrate. For purposes of the subject matter disclosed herein, the structured substrate may be manufactured by any of the processing methods known in the art, including, but not limited to, photolithography, lithography with electron beam, and ion grinding. In some embodiments, the coating step comprises a coating step by centrifugation. In some embodiments, the perfluoropolyether precursor comprises poly (tetrafluoroethylene oxide co-difluoromethylene oxide) a,? diol In some embodiments, the photoinitiator comprises 2,2-dimethoxy-2-phenyl acetophenone. In some embodiments, light-cured perfluoropolyether comprises a perfluoropolyether dimethacrylate. In some embodiments, the light-cured perfluoropolyether comprises a perfluoropolyether distirhenic. As has been recognized by one skilled in the art, perfluoropolyethers (PFPE) have been in use for more than 25 years for many applications. Commercial PFPE materials are produced by the polymerization of perfluorinated monomers. The first member of this class was produced by cesium fluoride catalyzed polymerization of hexafluoropropene oxide (HFPO) yielding a series of branched polymers designated as Krytox® (DuPont, Wilmington, Delaware, United States of America). A similar polymer is produced by the UV-catalyzed photooxidation of hexafluoropropene (Fomblin® Y) (Solvay Solexis, Brussels, Belgium). In addition, a linear polymer, (Fomblin® Z) (Solvay) is prepared by a similar process, using tetrafluoroethylene. Finally, a fourth polymer (Demnum®) (Daikin Industries, Ltd., Osaka, Japan) is produced by polymerization of tetrafluorooxethane followed by direct fluorination. The structures of these fluids are presented in Table I. Table II contains data specific to some members of the PFPE lubricant class. In addition to those commercially available PFPE fluids, a new series of structures is being prepared by direct fluorination technology. The representative structures of these new PFPE materials appear in Table III. The PFPE fluids mentioned above, only in Krytox® and Fomblin® Z have been used exhaustively in applications. See Jones, W.R., Jr., The Properties of Perfluoropolyethers Used for Space Applications, NASA Technical Memorandum 106275 (July 1993), which is hereby incorporated by reference in its entirety. Accordingly, the use of those PFPE materials is provided in the subject matter disclosed herein.

Table I Chemical Names and Structures of commercial PFPE fluids, Name Structure Demnum® C3F7O (CF2CF2CF2O) xC2F5 Krytox® C3F7O [CF (CF3) CF2O] xC2F5 Fomblin® Y C3F70 [CF (CF3) CF2O] x (CF2O) and C2F5 Fomblin® Z CF30 (CF2CF20) x (CF20) and CF3 Table II. Physical Properties of the PFPE Z-25 Kryton® 3700 230 113 -40 IdxIO6 3XI04 143AB Krytox® 6250 800 134 -35 2X108 dxio6 143AC Demnum® 8400 500 210 -53 ixis10 ixis7 s-200 Table III. Names and Chemical structures of PFPE Fluids Representative Name Structure Perfluoropoii (methylene oxide) (PMO) CF30 (CF20) xCF3 Perfluoropoly (ethylene oxide) (PEO) CF3O (CF2CF20) xCF3 Perfluoropoly (dioxolane (DIOX) CF3O (CF2CF2OCF2O) xCF3 Perfluoropoly (trioxocane) (TRIOX) CF30 { (CF2CF20) 2CF20] xCF3 where x is any integer, In some embodiments, ultraviolet radiation has a wavelength of approximately 365 nanometers. In some embodiments, the period of time at which the structured coated substrate is exposed to ultraviolet radiation ranges from about 1 second to about 300 seconds. In some embodiments, the period of time at which the structural substrate is separated is exposed to ultraviolet radiation ranging from about 1 second to about 100 seconds. In some modalities, the period of time at which the coated substrate, structure is exposed to the ultraviolet variation is approximately 6 seconds. In some embodiments, the period of time at which the structured coated substrate is exposed to the ultraviolet variation is approximately 60 seconds. In some embodiments, the structured layer of the structured perfluoropolyether is about 0.1 microns and about 100 microns thick. In some embodiments, the structured layer of the perfluoropolyether is approximately 0.1 millimeters and approximately 10 millimeters thick. In some embodiments, the structured layer of the light-cured perfluoropolyether is about 1 micrometer and SO micrometer thick. In some embodiments, the structured layer of the light-cured perfluoropolyether is approximately 20 micrometers thick. In some embodiments, the structured layer of the light-cured perfluoropolyether is approximately 5 millimeters thick. In some embodiments, the structured layer of the light-cured perfluoropolyether comprises a plurality of channels on a microscopic scale. In some embodiments, the channels have a width ranging from about 0.01 μm to about 1000 μm, a width ranging from about 0.05 μm to about 1000 μm; and / or a width that ranges from about 1 μm to about 100 μm. In some embodiments, the channels have a width ranging from about 1 μm to about 500 μm, a width ranging from about 1 μm to about 250 μm; and / or a width that ranges from about 10 μm to about 200 μm. Exemplary channel widths include, but are not limited to, 0.1 μm, 1 μm, 2 μm, 5 μm, 10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm , 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm, 190 μm, 200 μm, 210 μm, 220 μm, 230 μm, 240 μm, and 250 μm. In some embodiments, the channels have a depth ranging from about 1 μm to about 1000 μm; and / or a depth ranging from about 1 μm to about 100 μm. In some embodiments, the channels have a depth ranging from about 0.01 μm to about 1000 μm; a depth ranging from about 0.05 μm to about 500 μm; a depth ranging from about 0.2 μm to about 250 μm; a depth ranging from about 1 μm to about 100 μm; a depth ranging from about 2 μm to about 20 μm; and / or a _ depth that_ fluctuates from. approximately 5. μm to approximately 10 μm. Channel depths include but are not limited to 0.01 μm, 0.02 μm, 0.05 μm, 0.1 μm, 0.2 μm, 0.5 μm, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 7.5 μm, 10 μm, 12.5 μm, 15 μm, 17.5 μm, 20 μm, 22.5 μm, 25 μm, 30 μm, 40 μm, 50 μm, 75 μm, 100 μm, 150 μm, 200 μm, and 250 μm. In some embodiments, the channels have a width to depth ratio ranging from about 0.1: 1 to about 10O: 1. In some embodiments, the channels have a width to depth ratio ranging from about 1: 1 to about 50: 1. In some embodiments, the channels have a width to depth ratio ranging from about 2: 1 to about 20: 1. In some embodiments, the channels have a width ratio with a depth ranging from about 3: 1 to about 15: 1. In some embodiments, the channels have a width to depth ratio of approximately 10: 1. One skilled in the art will recognize that the dimensions of the channels of subject matter disclosed herein are not limited to the exemplary ranges described hereinafter and may vary in width and depth to affect the amount of force required to flow a material. through the channel and / or actuate a valve to control the flow of material in the. In addition, as described in more detail here below, wider channels were contemplated to be used as the fluid reservoir, a reaction chamber, a mixing channel, a separation region and the like. II.B. Method to Form a Multifilated Structured Perfluoropolyether Material of Multiple Layers. In some embodiments, the subject matter disclosed herein discloses a method for a structured, multi-layered, light-cured, perfluoropolyether material. In some embodiments, the structured, multi-layer, light-cured perfluoropolyether material is used to make a microfluidic device based on monolithic PFPE. Referring now to Figures 2A-2D, a schematic representation of the preparation of a modality of the subject matter disclosed herein is shown. Structured layers PL1 and PL2 are provided each comprising a perfluoropolyether material. In this example, each of the layer structures PL1 and PL2 comprises CH channels. In this embodiment of the subject matter disclosed herein, CH channels are channels on a microscopic scale. In the structured layer PL1, the channels are represented by a broken line, that is, as in Figures 2A-2C. The structure layer PL2 is superimposed on the structured layer PL1 in a predetermined alignment. In this example, the predetermined alignment is such that the CH channels in the structured layer PL1 and PL2 are substantially perpendicular to each other. In some embodiments, as described in Figures 2A-2D, the structured layer PL1 is superimposed on the unstructured layer NPL. The unstructured layer NPL may comprise a perfluoropolyether. Continuing with reference to Figures 2A-2D, the structured layers PL1 and PL2, and in some embodiments the unstructured layer NPL are exposed to UV light. The exposure of layers PL1 and PL2 and, in some embodiments, the unstructured layer NPL to ultraviolet UV light provides the adhesion of the structured layers PLl and PL2 to each other, and in some embodiments, the structured layer PL1 to the layer does not structured NPL, as shown in Figures 2C and 2D. The resulting microfluidic device MD comprises an integrated network IN of CH microscopic scale channels which intersect at predetermined intercept points, as best seen in the cross section provided in Figure 2D. Also shown in Figure 2D is the membrane M comprising the upper surface of the CH channels of the structured layer PL1 which separates the CH channel from the structured layer PL2 from the CH channels of the structured layer PL1. Continuing with reference to Figures 2A-2C, in some embodiments, the structured layer PL2 comprises a plurality of orifices, the orifices are intended as an inlet opening IA the outlet opening OA. In some embodiments, the orifices, the inlet opening IA and the outlet opening OA are in fluid communication with the CH channels. In some embodiments, as shown in Figures 5A and 5B as will be discussed in greater detail hereinafter, the orifices comprise a laterally actuated valve structure comprising a membrane of PFPE material and can be operated to restrict flow in uri splice channel. Accordingly, in some embodiments, the subject matter disclosed herein discloses a method for forming a multilayer, structured, light-cured perfluoropolyether material, the method comprising: (a) superposing a first structured layer of the light-cured perfluoropolyether on a second structured layer of the light-cured perfluoropolyether, wherein the patterns of the first and second layers of light-cured perfluoropolyether are aligned in a predetermined alignment; and (b) exposing the first and second layer of the photocured perfluoropolyether to ultraviolet radiation for a period of time. In some embodiments, the first structured layer of light-cured PFPE material is emptied to such a thickness as to impart a degree of mechanical stability to the PFPE structure. Accordingly, in some embodiments, the first structured layer of the light-cured PFPE material is about 50 μm to several centimeters in thickness. In some embodiments, the first structured layer of the light-cured PFPE material is between 50 μm and approximately 10 millimeters thick. In some embodiments, the first structured layer of the light-cured PFPE material is 5 mm thick. In some embodiments, the first structured martial layer of PFPE is approximately 4 mm thick. In addition, in some embodiments, the thickness of the first structured layer of the PFPE material ranges from about 0.1 μm to about 10 cm; from about 1 μm to about 5 cm; from about 10 μm to about 2 cm; and from about 100 μm to about 10 mm. In some embodiments, the second structured light-cured PFPE material is about 1 micrometer and up to about 100 micrometers thick. In some embodiments, the second structured layer of the light-cured PFPE material is about 1 micrometer and about 50 micrometers thick. In some embodiments, the second structured layer of the light-cured material is approximately 20 micrometers thick. Although Figures 2A-2C and Figure 13 describe the formation of a microfluidic device where two structural layers of PFPE material are combined, in some embodiments of the subject matter disclosed herein it is possible to form a microfluidic device comprising a structured layer. and an unstructured layer of PFPE material. In this way, the first structured layer may comprise a microscopic scale channel or an integrated network of channels on a microscopic scale and then the first structured layer may be placed on the unstructured layer and adhered to the unstructured layer using the light curing step , as the application of ultraviolet use as described herein, to form a monolithic structure comprising closed channels therein.

Accordingly, in some embodiments, a first and a second structured layer of light-cured perfluoropolyether material, or alternatively a first structured layer of light-cured perfluoropolyether material and an unstructured layer of light-cured perfluoropolyether material, adhere to each other, thereby forming a microfluidic device based on monolithic PFPE. III. Method to Direct the Flow of a Material through a Microfluidic Device Based on PFPE. In some embodiments, the subject matter disclosed herein describes a method for directing a flow of a material through a microfluidic device based on PFPE. In some embodiments, the method of directing the flow of material through a PFPE-based mocrofluidic device comprises actuating a valve structure or a plurality of valve structures within the microfluidic device. In some embodiments, the valve structure comprises a portion of the microfluidic channel itself. In some embodiments, the valve structure further comprises a laterally actuated valve. III.A. Method for Acting a Valve Structure Within a Microfluidic Device Based on PFPE. In some embodiments, the method of actuating a valve structure within a microfluidic device based on PFPE comprises closing a first flow channel by applying pressure to a second junction flow channel (or "control channel"), bypassing both a thin membrane of PFPE material separating the two channels towards the first flow channel. Figures 3A and 3B together show the closure of a first flow channel by pressurizing a second flow channel. Referring now to FIGS. 3A, there is shown a front-cut view of a microfluidic device based on monolithic PFPE 300 comprising a structured, multi-layered PFPE material 310 adhered to the flat, unstructured PFPE layer 312. first flow channel 320 and second flow channel 322 are separated by membrane 314, which forms the upper part of first flow channel 320 and lower portion of second flow channel 322. As described in Figures 3A, the flow channel 320 is open. Referring now to Figure 3B, pressurization of the flow channel 322 (either by a gas or a fluid introduced therein) causes the membrane 314 to deviate downward, thereby resisting the flow F, as shown in FIG. Figure 3A, which stops through the flow channel 320. Accordingly, by varying the pressure in the channel 322, a valve system operable is provided so that the flow channel 320 can be substantially open or substantially closed in one position open or closed intermediate diverted membrane 314 when desired. For purposes of illustration, only channel 320 in Figure 3B is shown in a "substantially closed" position, rather than a "fully closed" position. In some embodiments, the membrane 314 of the PFPE material separating the overlapped channels 320 and 322 has a thickness of between about 0.01 Dm and 1000 Dm, from about 0.05 μm to 500 μm, from 0.2 μm to 250 μm, from 1 μm to 100 μm, from 2 μm to 50 μm and from 5 μm to 40 μm. Exemplary membrane thicknesses include, but are not limited to, 0.01 μm, 0.02 μm, 0.03 μm, 0.05 μm, 0.1 μm, 0.2 μm, 0.3 μm, 0.5 μm, 1 μ, 2 μm, 3 μm, 5 μm, 7.5 μm, 10 μm, 12.5 μm, 15 μm, 17.5 μm, 20 μm, 22.5 μm, 25 μm, 30 μm, 40 μm, 50 μm, 75 μm, 100 μm, 150 μm, 200 μm, 250 μ, 300 μm , 400 μm, 500 μm, 750 μm, and 1000 μm. Because the valves are driven by moving a portion of the channels themselves (i.e., bypassing the membrane 314) and do not require additional components, the valves and pumps produced by this technique have a dead volume of zero, and the switching valves made by this technique have a dead volume approximately equal to the active volume of the valve, for example, of approximately 100 μm x 100 μm x 10 μm = 100 pL. These dead volumes and areas consumed by the mobile membrane are about 2 orders of magnitude smaller than known conventional microvalves. Smaller and larger valves are provided in the subject matter disclosed herein, including, but not limited to, valves that comprise a dead volume that ranges from 1 to a? μL; 100 aL to 100 nL; 1 fL to 1 nL; 100 fL to 1 nL; and 1 pL to 100 pL. The small volume of materials, such as a fluid, that can be provided by the pumps and valves in accordance with the subject matter disclosed herein represents a substantial advantage over pumps and valves known in the art. For example, the smallest known volume of a fluid capable of being dosed manually is approximately 0.1 μl. In addition, the smallest known volume of a fluid capable of being dosed by automated systems is approximately 1 μL. Using pumps and valves in accordance with the subject matter disclosed herein, a volume of fluid comprising 10 nL or less can be dosed and distributed. Accurate dosing of extremely small volumes of fluid allowed by the subject matter disclosed herein can be extremely valuable in a large number of biological applications, including the synthesis on a microscopic scale of biological materials, such as DNA, and diagnostic tests and assays. . As described in U.S. Patent No. 6,408,878 to Unger et al. which is incorporated herein by reference in its entirety, the deflection of an elastomeric membrane in response to a pressure is a function of: the length, width, and thickness of the membrane, the flexibility of the membrane, for example, as arranged by its Young's modulus, and the applied driving force. Because each of these parameters will vary depending on the dimensions and physical composition of a particular elastomeric device, for example, a PFPE device in accordance with the subject matter disclosed herein, a wide range of membrane thicknesses are provided, channel widths and drive forces. The pressure can be applied to drive the membrane of the device by passing a fluid or gas, such as air, through, for example, a first piece of pipe connected to a second, narrower piece of pipe, like a hypodermic pipe, for example, a hypodermic metal needle, wherein the hyopodermic needle is brought into contact with the flow channel by insertion into the PFPE block in a direction normal to the flow channel. Accordingly, in some embodiments, the method for driving a microfluidic device based on PFPE further comprises forming a plurality of holes in at least one structured layer of the light-cured perfluoropolyether material. In some embodiments, as shown in Figure 2A, at least one of the plurality of orifices comprises an inlet opening IA. In some embodiments, as also shown in Figure 2A, at least one of the plurality of orifices comprises an exit opening OA. In addition, that embodiment solves a number of problems possessed by the connection of a conventional microfluidic device to an external fluid source. One such problem is the fragility of the connection between the microfluidic device and the external fluid source. Conventional microfluidic devices comprise hard, inflexible materials, such as silicon, to which a pipe that provides a connection to an external element must be attached. The rigidity of conventional materials creates a physical effort at the points of contact with the external pipe, making the conventional microfluidic device prone to fractures and leaks at those points of contact. In contrast, the PFPE material of the subject matter disclosed herein is flexible and can be penetrated for external connection by a rigid tube, such as a hypodermic metal needle, comprising a pure material. For example, in a PFPE structure made using the method shown in Figures 1 and 2, an orifice extending from the exterior surface of the structure toward the flow channel, as shown in Figures 2A-2C, can be produced. penetrating the outer surface of the structured layer of the PFPE material with the hypodermic metal needle after the top layer of the PFPE material has been removed from the mold (as shown in Figure 1C) and before this layer has been attached to the second structured layer of the PFPE material (as shown in Figure 2A-2C). Between those steps, a portion of the flow channel is exposed to the user's view and is accessible for insertion of the hypodermic needle and proper placement of the hole. After completing the fabrication of the device, the hypodermic metal needle is inserted into the hole to complete the fluidic connection to the external fluid source. In addition, the PFPE material of the subject matter disclosed herein will flex in response to deformation or physical stress at the point of contact with an external connection, making the external physical connection more robust. This flexibility substantially reduces the probability of leakage or fracture of the microfluidic device currently described. Another disadvantage of conventional microfluidic devices is the difficulty of establishing an effective seal between the device and its connections to an external fluid flow. Due to the narrow channel diameter that is typical of these microfluidic devices, achieving even moderate fluid flow rates may require high inlet pressures. As a result, undesirable leakage may result at the point of contact between the device and an external connection. The flexibility of the PFPE material from which the microfluidic device disclosed herein is manufactured helps to prevent leakage related to high inlet pressures. More particularly, the flexible PFPE material conforms to the shape of the inserted pipe to form a substantially pressure resistant seal. Although control of the flow of material through the device has been described using an applied gas pressure, other fluids may be used. A gas is compressible, and thus it experiences some finite delay between the time of application of pressure, for example, of an external solenoid valve and the time at which this pressure is experienced by the membrane separating the flow channels of the microfluidic device. Accordingly, in some embodiments of the subject matter disclosed herein, pressure is applied from an external source to a non-compressible fluid, such as water, or a hydraulic oil, resulting in an almost instantaneous transfer of the pressure applied to the membrane. If the displaced volume of the membrane is large or the flow channel is narrow, the high viscosity of the control fluid may contribute to the delay of the drive. Therefore, the optimum means for transferring pressure will depend on the application and configuration of the particular device. Accordingly, the use of gaseous and liquid media to drive the deflectable membrane is provided by the subject matter disclosed herein. In some embodiments, external pressure is applied by a pump and tank system through a pressure regulator and external valve. As will be understood by one skilled in the art, other external pressure application methods are provided with the subject matter disclosed herein, including gas tanks, compressors, piston systems, and liquid columns. They are also provided for use in the subject matter disclosed by the - - present natural sources of pressure, such as those found within living organisms, including blood pressure, gastric pressure, pressure present in the cerebrospinal fluid, pressure present in the intraocular space, and the pressure exerted by the muscles during flexion. Other methods are also provided to regulate external pressure by the subject matter disclosed herein, including miniature valves, pumps, pumps macroscopic peristaltics, clamping valves and other types of fluid regulating equipment such as those known in the art. In some embodiments, the response of microfluidic valves according to the subject matter revealed by The present is almost linear over a substantial portion of this travel distance, with minimal hysteresis, see U.S. Patent No. 6,408,878 to Unger et al. , which is incorporated here as a reference in its entirety. Accordingly, the valves according to the subject matter disclosed herein are ideally suited for microfluidic dosing and fluid control. Although the valves and pumps of the subject matter disclosed herein do not require linear actuation to open and close, a linear response facilitates the use of the valves as dosing devices. In some embodiments, the opening of the inlet is used to control a flow rate until it is partially driven to a known degree of closure. The actuation of the linear valve also facilitates the determination of the amount of driving force required to close the valve to a desired degree of closure. Another benefit of the linear drive is that the force required for actuating the valve can be determined from the pressure in the flow channel. Accordingly, if the action is linear, an increased pressure in the flow channel can be found by adding the same pressure (force per unit area) to the actuated portion of the valve. In this way, high pressures can be found in the flow channel (i.e., back pressure) by increasing the actuating pressure. The linearity of the response of a valve depends on the structure, composition and operating method of the valve structure. Also, if linearity is a desirable characteristic in a valve it depends on the application. Therefore, linearly and non-linearly operable valves are provided in the subject matter disclosed herein, and the pressure fluctuates over which a valve is linearly operable and will vary with the specific mode. In addition to the pressure-based drive systems described hereinabove, electrostatic and magnetic drive systems are also provided by the subject matter disclosed herein. For example, the electrostatic drive can be effected by forming oppositely charged electrodes (which will tend to attract each other when a voltage difference is applied to them) directly to the monolithic PFPE structure. Referring again to Figure 3A, a first electrode 330A (shown in shaded form) can be placed on (or in) the membrane 314 and a second electrode 330B (also shown in shaded form) can be placed on (or in) the layer of flat unstructured PFPE 312. When the electrodes 330A and 330B are charged with opposite polarities, an attractive force between the two electrodes will cause the membrane 314 to bend downwardly, thereby closing the flow channel 320. In order for the The membrane electrode is sufficiently conductive to support the electrostatic actuation, so as not to mechanically stiffen it so as to impede the movement of the membrane, a sufficiently flexible electrode must be provided in or on the membrane 314. That sufficiently flexible electrode can be provided by depositing a layer of thin metallization on the membrane 314, by adulterating the polymer with conductive material, or by making the outer surface layer of a conductive material. In some embodiments, the electrode present in the deflection membrane is provided by a thin metallization layer, which can be provided, for example, by electroplating a thin metal layer, such as 20 nm of gold. In addition to the formation of a metallized electrodeposition membrane, other metallization methods are also available, such as chemical epitaxy, evaporation, electrocoating and coating without electrodes. The physical transfer of a metal layer to the surface of the elastomer is also available, for example, by evaporating a metal on a flat substrate to which it adheres poorly, and then placing the elastomer on the metal and peeling the metal from the substrate. The conductive electrode 330A can also be formed by depositing carbon black (eg, Vulcan® XC72R Cabot Corporation, Boston, Massachusetts, United States of America) on the elastomeric surface. Alternatively, the electrode 330A can be formed by constructing the entire structure 300 of the adulterated elastomer with conductive materials (ie, carbon black or finely divided metal particles). The electrode can also be formed by electrostatic deposition, or by a chemical reaction that produces carbon. The lower electrode 330B, which is not required to move, may be an adaptive electrode as described above, or a conventional electrode, such as evaporated gold, a metal plate, or an adulterated semiconductor electrode. In some embodiments, the magnetic drive of the flow channels can be achieved by fabricating in the membrane that separates the flow channels with a magnetically polarizable material, such as iron, or a permanently magnetized material, such as polarized NdFeB. In embodiments, where the membrane is made of a magnetically polarizable material, the membrane can be driven by attraction in response to an applied magnetic field. In embodiments where the membrane is made of a material capable of maintaining a permanent magnetization, the material can be magnetized first by exposing itself to a sufficiently high magnetic field, and then it will be driven by attraction or repulsion in response to the plurality of a non-homogeneous magnetic field applied. The magnetic field produced by the drive of the membrane can be generated in a variety of ways. In some embodiments, the magnetic field is generated by a small injector coil formed on or near the elastomeric membrane. The actuation effect of that magnetic coil is localized, thereby allowing the actuation of a pump and / or individual valve structure. In some embodiments, the magnetic field is generated by a larger, or more powerful, source in which the drive is not located and can drive pumps and / or multiple valve structures simultaneously. In addition, it is possible to combine pressure drive with electrostatic or magnetic drive. More particularly, a bellows structure in fluid communication with a cavity and / or channel could be electrostatically or magnetically driven to change the pressure in the cavity and / or channel and thereby actuate a membrane structure adjacent to the cavity and / or channel. In addition to the electric or magnetic drive as described above, electrolytic and electrokinetic drive systems are also provided by the subject matter disclosed herein. For example, in some embodiments, the actuation pressure on the membrane arises from an electrolytic reaction in a cavity and / or channel superimposed on the membrane. In that embodiment, the electrodes present in the cavity and / or channel apply a voltage through an electrolyte in the cavity and / or channel. This potential difference produces an electrochemical reaction in the electrodes and results in the generation of gas species, resulting in a pressure difference in the cavity and / or channel. In some embodiments, the actuation pressure on the membrane arises from an electrokinetic fluid flow in the control channel. In this embodiment, the electrodes present at the opposite ends of the control channel apply a potential difference between an electrolyte present in the control channel. The migration of charged species in the electrolyte to the respective electrodes results in a pressure difference. In some modalities, it is. possible to operate the device producing a. Fluid flow in the control channel based on the application of thermal energy, either by thermal expansion or by production of a gas from a liquid. Similarly, chemical reactions that generate gaseous products can produce an increase in pressure sufficient to drive the membrane. III.B. Method of Acting a Valve Structure Inside a Microfluidic Device Based on PFPE that Includes Flow Channels of Different Sizes and Ways of Cross Section. In some embodiments, the subject matter disclosed herein describes flow channels comprising different sizes and cross-sectional shapes, which offer different advantages depending on their desired application, in particular, advantages with respect to the sealing of a flow channel. For example, the shape of the cross section of the lower flow channel may have a curved upper surface, either along its entire length or in the region deposited under the upper transverse channel. Referring now to Figure 4A, there is shown a cross-sectional view similar to that of Figure 3A of the flow channels 320 and 322. In this embodiment, the flow channel 320 is of rectangular cross-sectional shape. In some embodiments, as shown in Figure 4B, the cross section of the flow channel 320 has a curved upper surface as described by 320A. Referring again to Figure 4A, when the flow channel 322 is pressurized, the portion of the membrane 314 that separates the flow channels 320 and 322 will move downward to the successive positions shown by the dotted lines 314B, 314C, 314D, and 314E. In some cases, an incomplete seal may occur at the edges of the rectangular flow channel 320 and the adjacent flat unstructured PFPE layer 312.

Referring again to Figure 4B, the flow channel 320A has a curved top surface 314A. When the flow channel 322 is pressurized, the portion of the membrane 314 will move downward to the successive positions shown by the dotted lines 314A2, 314A3, 314A, and 314A5, with the portions of the edge of the membrane moving first toward the channel. flow, followed by the upper portions of the membrane. An advantage of having that curved top surface in the membrane 314 is that a more complete seal will be provided when the flow channel 322 is pressurized. More particularly, the upper surface of the flow channel 320A will provide a continuous contact edge against the unstructured PFPE layer 312, thereby preventing the incomplete contact observed between the membrane 314 and the bottom of the flow channel 320 in the Figure 4A. Another advantage of having a curved upper flow channel surface in the membrane 314 is that the membrane can easily conform to the shape and volume of the flow channel in response to the drive. More particularly, when a rectangular flow channel is used, the entire perimeter (2 x height of the flow channel, plus the width of the flow channel) must be forced into the flow channel. When a curved flow channel is used, a smaller perimeter of material (only the semicircular arcuate portion) must be forced into the channel. In this way, the membrane requires less change in the perimeter for the drive and therefore responds more to an applied driving phase to close the flow channel. In some embodiments, (not illustrated), the bottom of the flow channel 320 is rounded, so that its curved surface engages the upper curved surface 314A as seen in Figure 4B as described above. In particular, the actual conformational change experienced by the membrane upon activation will depend on the configuration of the particular PFPE structure. More particularly, the conformational change will depend on the length, width and profile of the thickness of the membrane, its attachment to the rest of the structure, and the height, width and shape of the flow channels and control of the properties of the membrane. PFPE material used. The conformational change also depends on the driving method, since the actuation of the membrane in response to an applied pressure will vary somewhat from the drive in response to magnetic or electrostatic force. In addition, the desired conformational change in the membrane will also vary depending on the particular application of the PFPE structure. In the modalities described above, the valve can be opened or closed, when dosed to control the degree of closure of the valve. Many membrane thickness profiles and flow channel cross sections are provided by the subject matter disclosed herein, including rectangular, trapezoidal, circular, ellipsoidal, parabolic, hyperbolic and polygonal, as well as sections of the forms mentioned above. The more complex cross-sectional shapes, such as the mode with projections described immediately above or a modality comprising concavities in the flow channel, are also provided by the subject matter disclosed herein. III "» C. ~ - Method of -Adjusting a Valve Structure Laterally Operated In some embodiments, the subject matter disclosed herein comprises a laterally actuated valve structure. Referring now to Figures 5A and 5B, Figure 5A shows a laterally actuated valve structure 500 in an unactuated position. The flow channel 510 is formed in the PFPE layer 502. The control channel 512 that is connected to the flow channel 510 is also formed in the PFPE layer 502. In some embodiments, the control channel 512 comprises an "orifice". "formed, for example, piercing the PFPE layer with a hypodermic needle as described here above. The control channel 512 is separated from the flow channel 510 by a membrane portion of PFPE 504. A second layer of PFPE (not shown) is bonded to the lower PFPE layer 502, for example by photocuring, to enclose the channel flow 510 and control channel 512. Figure 5B shows a laterally actuated valve structure 500 in an actuated position. In response to the pressure, or other actuation technique, within the control channel 512, the membrane 504 deforms to the flow channel 510, blocking the flow channel 510. After releasing the pressure within the control channel 512, the membrane 504 relaxes again to control channel 512 and opens the flow channel 510. Although a valve structure actuated laterally in response to pressure is shown in FIGS. 5A and 5B, a valve operated laterally in accordance with with the subject matter disclosed herein is not limited to this configuration In some embodiments, the membrane portion of PFPE located between the flow channel and splice control is manipulated by the electric or magnetic fields, as described hereinabove. IIItD - Method of Activation of an Integrated Network of Channels at Microscopic Scale Comprising a Microfluidic Device Based on PFPE In some embodiments, the predetermined alignment The first and second layers of the light-cured perfluoropolyether material form a plurality of channels on a microscopic scale. In some embodiments, the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. In some embodiments, the microscopic-scale channels of the integrated network intersect at predetermined intersection points. Referring now to Figures 6A and 6B, there is shown a schematic view of a plurality of flow channels which are controllable by a single control channel. The system is comprised of a plurality of individual addressable on / off valves multiplexed together. More particularly, a plurality of parallel flow channels 320A, 320B and 320C are provided The flow channel 322 (ie, a "control line") passes over the flow channels 320A, 320B and 320 C. Pressurization of control line 322 simultaneously interrupts flows Fl, F2 and F3 by pressing membranes 314A, 314B and 314C located at the intersections of control line 322 and flow channels 320A, 320B and 320C. Now to Figure 7, there is shown a schematic illustration of a multiplexing system adapted to allow the flow of fluid through selected channels, comprised of a plurality of individual on / off valves, joined or interconnected together as shown. plurality of parallel flow channels 320A, 320B, 320C, 320D, 320E and 320F are placed under a plurality of parallel control lines 322A, 322B, 322C and 322D.The control channels 322A, 322B, 322C and 322 2D are operated to interrupt the fluid flows Fl, F2, F3, F4, F5 and F6 which pass through the parallel flow channels 320A, 320B, 320C, 320D, 320E and 320F using any of the valve systems described above , with the following modification. The downward deflection of the membranes separating the respective flow channels from a control line passing therethrough (eg, membranes 314A, ~ 314B ~ and ~ 314C in Figures 6A and 6B) depends on the dimensions of the membrane. Accordingly, by varying the widths of the control line of the flow channel 322 in Figures 6A and 6B, it is possible to cause a control line to pass over multiple flow channels, by driving (ie, closing) only the channels still of desired flow. Each of the control lines 322A, 322B, 322C and 322D has a wide and a narrow portion. For example, the control line 322A is wide at the places placed on the flow channels 320A, 320C, and 320E. Similarly, the control line 322B is wide in the places deposited on the flow channels 320B, 320D and 320F, and the control line 322C is wide in the places placed on the flow channels 32OA, 320B, 320E and 320F .

In the places where the respective control line is wide, its pressurization causes the membrane 314 that separates the flow channel and the control line (as shown in Figure 6B) to be pressed significantly towards the flow channel, blocking by so the flow passage through it. On the contrary, at the place where the respective control line is narrow, the membrane 314 is also narrow. Accordingly, the same degree of pressurization will not result in the membrane 314 being pressed into the flow channel 320. Therefore the passage of fluid under it will not be blocked. For example, when the control line 322A is pressurized, it blocks the flows Fl, F3 and F5 in the flow channels 320A, 320C and 320E, respectively. Similarly, when the control line 322C is pressurized, it blocks the flows Fl, F2, F5 and F6 to the flow channels 320A, 320B, 320E and 320F, respectively. As will be appreciated by one skilled in the art upon review of the present disclosure, more than one control line may be operated at the same time. For example, control lines 322A and 322C can be pressurized simultaneously to block all fluid flow except F4 (with control line 322A blocking Fl, F3 and F5, and control line 322C blocking Fl, F2, F5 and F6). By selectively pressurizing the different control lines 322A-D both together and in several sequences, a degree of fluid flow control can be achieved. Further, by extending the present system to more than six parallel flow channels 320A-F and more than four parallel control lines 532A-D, and varying the placement of the wide and narrow regions of the control lines, they can manufacture complex fluid flow control systems. IV. Method of Use of a Microfluidic Device Based on PFPE 0 In some embodiments, the subject matter disclosed herein describes a method for flowing a ~ "material" and / or "effecting a chemical reaction in a microfluidic device based on PFPE In some embodiments, the subject matter disclosed herein describes a method for synthesizing a biopolymer, such as DNA. , the subject matter disclosed herein discloses a method for selecting a sample by a characteristic In some embodiments, the subject matter disclosed herein discloses a method for distributing the material In some embodiments, the subject matter disclosed herein describes a method for separating a material IV.A. Method for Flowing a Material and / or Performing a Chemical Reaction in a Microfluidic Device Based on PFPE 5 In some embodiments, the subject matter disclosed herein describes a method for making flow a material and / or effect a chemical reaction in a microfluidic device based on PFPE. Referring now to Figure 8, it shows a schematic plan of a microfluidic device of the subject matter disclosed herein. The microfluidic device is generally referred to as 800. The microfluidic device 800 comprises a structured layer 802, and a plurality of holes 810A, 810B, 810C and 810D. These holes can best be described as the inlet opening 810A, the inlet opening 810B and the inlet opening 810C and the outlet opening 810D. Each of the openings 810A, 810B, 810C and 810D are covered by seals 820A, 820B, 820C and 820D, which are preferably reversible seals. Seals 820A, 820B, 820C and 820D are provided in a manner that materials, including but not limited to, solvents, chemical reagents, components of biochemical systems, samples, inks and reaction products and / or solvent mixtures, chemical reagents, components of a biochemical system, samples, inks, reaction products and combinations thereof, may be stored, transported, or otherwise maintained in the microfluidic device 800 if desired. The seals 820A, 820B, 820C and 820D can be reversible, ie, removable, so that the microfluidic device 800 can be implemented in a chemical reaction or other use and then resealed if desired. Continuing with reference to Figure 8, in some embodiments, openings 810A, 810B and 810C, further comprise pressure-operated valves (comprising intersecting, intersecting flow channels, not shown) which can be actuated to seal the associated microfluidic channel with the opening .. Continuing with reference to Figure 8, the structured layer 802 of the microfluidic device 800 comprises an integrated network 830 of channels on a microscopic scale. The integrated network 830 comprises this mode a series of flux-connected microscopic-scan channels-designated by the following reference characters: 831, 832, 833, 834, 835, 836, 837, 838, 839, and 840. In this way, the inlet opening 810A is in fluid communication with the microscopic scale channel 831 which extends away from the opening 810A and is in fluid communication with the microscopic scale channel 832 via an elbow. An integrated network 830 described in Figure 8 shows a series of 90 ° elbows for convenience. It should be noted, however, that the paths provided in the channels of the integrated network 830 can encompass any configuration, angle or other desired feature. In reality, reservoirs of fluid 850A and 850B can be provided along microscopic scale channels 831, 832, 833 and 834, respectively, if desired. As shown in Figure 8, fluid reservoirs 850A and 850B comprise at least one dimension that is greater than the dimension of the channels that are immediately adjacent to them. Continuing, then, with reference to Figure 8, the microscopic-scale channels 832 and 834 intersect at the 860A intersection point and proceed to a single-microscopic-scale channel 835. The microscopic-scale channel 835 proceeds to a 870-chamber , which in the modality shown in Figure 8, is sized to be wider than the microscopic scale channel 835. In some embodiments, the - Chamber 870 comprises a reaction chamber. In some embodiments, the camera 870 comprises a mixing chamber.

In some embodiments, the camera 870 comprises a separation region. In some embodiments, the separation region comprises a given dimension, e.g., the length, of a channel, where the material is separated by charge, or mass, or combinations thereof, or any other physical characteristic where a separation may occur. over a given dimension. In some embodiments, the separation region comprises an active material 880. As will be understood by one skilled in the art, the term "active material" was used here for convenience and does not imply that the material must be activated to be used for its use. alleged. In some embodiments, the active material is a chromatographic material.

In some modalities, the active material is a target material. Continuing with Figure 8, it should be noted that the camera 870 does not necessarily need to be of a dimension wider than a channel at an adjacent microscopic scale. In reality, the camera 870 may simply comprise a given segment of a channel on a microscopic scale where at least two materials are separated, mixed and / or reacted. Extending from the chamber 870 substantially opposite to the microscopic scale channel 835 is the microscopic scale channel 836. The scale channel -microscopic- -836-forms a T-junction with the microscopic-scale channel 837 extending away from and is in fluid communication with the 810C aperture. In this way, the junction of the channels at microscopic scale 836 and 837 forms an intersection point 860B. The microscopic scale channels 838 extend from the intersection point 860B in a direction substantially opposite to the microscopic scale channel 837 and to the fluid reservoir 850C. The fluid reservoir 850C is dimensioned so that it is wider than the microscopic scale channel 838 by a predetermined length. As noted above, however, a given section of a channel on a microscopic scale can act as a reservoir of fluid without the necessity of necessarily changing a dimension of the channel section at a microscopic scale. In addition, the microscopic scale channel 838 could act as a reaction chamber in which a reagent flowing from the microscopic scale channel 837 to the 860B intersection could react with a reagent that moves from the 836 microscopic scale channel to the point intersection 860B in a microscopic scale channel 838. Continuing with reference to FIG. 8, the microscopic scale channel 839 extends from the fluid reservoir 850C substantially opposite the microfluidic channel 873 and travels through an elbow to the channel microscopic scale 840. The microscopic scale channel 840 is fluidically connected to the exit aperture 810D. The outlet opening 810D can be optionally reversible sealed via the seal 82OD as discussed above. Again, the reversible sealing of the outlet opening 810D may be desirable in the case of a mode where the reaction product is formed in the microfluidic device 800 and it is desired to be transported to another location in the microfluidic device 800. The flow of a material can be routed through the integrated network 830 of channels on a microscopic scale, including the channels, fluid reservoirs and reaction chambers, by the method described in Figure 7. Consequently, in some embodiments, the subject matter disclosed by The present invention comprises a method for flowing a material in a microfluidic device, the method comprising: (a) providing a microfluidic device comprising at least one structured layer of a light-cured perfluoropolyether, wherein the structured layer of the light-cured perfluoropolyether comprises at least one channel on a microscopic scale; and (b) flowing a material in the channel at a microscopic scale. In some embodiments, the method comprises depositing a material in the microfluidic device. In some modalities, as best shown in Figure 10 and As it is discussed, more detail is given below, the method comprises applying a driving force to move the material along the channel on a microscopic scale. In some embodiments, the method further comprises a plurality of channels on a microscopic scale. In some embodiments, the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. In some embodiments, the microscopic-scale channels of the integrated network intersect at predetermined points. In some embodiments, the structured layer of the light-cured perfluoropolyether comprises a plurality of holes. In some embodiments, at least one of the plurality of holes comprises an entry opening. In some embodiments, at least one of the plurality of holes comprises an exit opening. In some embodiments, the method comprises at least one pressure operated valve, wherein the pressure operated valve is defined by one of: (a) a channel on a microscopic scale; (b) at least one of the plurality of holes. In some embodiments, the pressure operated valve is actuated by introducing a pressurized fluid into one of: (a) a channel on a microscopic scale; . { b) at least one of the plurality of holes. In some embodiments, the pressurized fluid has a pressure of between about 0.703 kgf / cm2 (10 psi) and about 2.81 kgf / cm2 (40 psi). In some embodiments, the pressure is -about 1.75-kgf / cm2 (25 psi). In some embodiments, the material comprises a fluid. In some embodiments, the fluid comprises a solvent. In some embodiments, the solvent comprises an organic solvent. In some embodiments, the material flows in a predetermined direction along the channel at a microscopic scale. In addition, in some embodiments, the subject matter disclosed herein discloses a method for effecting a chemical reaction, the method comprising: (a) providing a microfluidic device having a structured layer of a light-cured perfluoropolyether; and (b) contacting a first reagent and a second reagent in the microfluidic device to form a reaction product. In some embodiments, the structured layer of the light-cured perfluoropolyether comprises a plurality of channels on a microscopic scale. In some embodiments, at least one of the microscopic-scale channels comprises a fluid reservoir. In some embodiments, at least one of the microscopic-scale channels comprises a fluid reaction chamber in fluid communication with the fluid reservoir. In some embodiments, the method further comprises making the first reagent and the second reagent flow in a predetermined direction in the microfluidic device. In some embodiments, the contact of the first reagent and the second reagent is carried out in a reaction chamber on a microscopic scale. In some embodiments, the method further comprises flowing the reaction product in a predetermined direction in the microfluidic device. In some embodiments, the method further comprises coating the reaction product. In some embodiments, the method further comprises flowing the reaction product towards an outlet opening of the microfluidic device. In some embodiments, the method further comprises contacting the reaction product with a third reagent to form a second reaction product. In some embodiments, the first reagent and the second reagent comprise an organic solvent, including, but not limited to, hexanes, ethyl ether, toluene, dichloromethane, acetone and acetonitrile. IV.B. Method for Synthesizing a Biopolymer in a Microfluidic Device Based on PFPE In some embodiments, the microfluidic device based on PFPE described herein can be used in the synthesis of biopolymers, for example, in the synthesis of oligonucleotides, proteins, peptides, DNA and Similar. In some modalitiesThese biopolymer synthesis systems comprise an integrated system comprising an array of reservoirs, fluidic logic to select the flow of a particular reservoir, and an array of channels, reservoirs and reaction chambers in which the synthesis is carried out. , and a fluid logic to determine to which channels the selected reagent flows. Referring now to Figure 9, a plurality of reservoirs, for example, reservoirs 910A, 910B, 910C and 910D, have bases A, C, T and G, respectively deposited therein, as shown. Four flow channels 320A, 320B, 320C and 320D are connected to reservoirs 910A, 910B, 910C and 910D. Four control channels 322A, 322B, 322C, 322D (shown in shaded form) are placed therethrough with control channel 322A allowing flow only through flow channel 32OA (i.e., sealing flow channels 320B, 320C, and 320D), when the control channel 322A is pressurized. Similarly, control channel 322B allows flow only through flow channel 320B when it is pressurized. Therefore, the selective pressurization of the control channels 322A, 322B, 322C and 322D sequentially selects a desired base A, C, T and G from the desired reservoir 910A, 910B, 910C or 910D. The fluid then passes through the flow channel 920 to the multiplexed channel flow controller 930 (including, for example, any system as shown in Figures 7 and 8), which at its "time" directs the -flow of fluid-to one or more of a plurality of synthesis channels or reaction chambers 940A, 940B, 940C, 940D or 940E in which solid phase synthesis can be carried out In some embodiments, instead of starting With the desired base A, C, T and G, a reagent selected from one of a nucleotide and a polynucleotide is deposited in at least one of the reservoirs 910A, 910B, 910C and 910 D. In some embodiments, the reaction product comprises a polynucleotide In some embodiments, the polynucleotide is DNA Therefore, after review of the present disclosure, one skilled in the art will recognize that the PFPE-based microfluidic device described herein can be used to synthesize biopolyme ros, as described in U.S. Patent Nos. 6,408,878 to Unger et al. and 6,729,352 to O'Conner et al., and / or in combined synthesis systems as described in U.S. Patent No. 6,508,988 to Van Dam et al. , each of which is incorporated here as a reference in its entirety. IV.C. Method for Incorporating a Microfluidic Device Based on PFPE in an Integrated Fluid Flow System In some embodiments, the method for effecting a chemical reaction or flowing a material within a microfluidic device based on PFPE involves incorporating the microfluidic device into a "system Integrated Fluid Flow Referring now to Figure 10, a system for carrying out a method for flowing a material in a microfluidic device and / or a method for effecting a chemical reaction in accordance with the disclosed subject matter is schematically described. The system itself is generally referred to as 1000. The system 1000 may comprise a central processing unit 1002, one or more control force controllers 1010A, 1010B, 10101C and 1010D, a collector 1020, and a detector 1030. In some embodiments, the detector 1030 is in fluid communication with the microfluidic device ( shown in a shaded way). The microfluidic device 1000 of Figure 8, and those reference numbers of Figure 8 are employed in Figure 10. The central processing unit (CPU) 1002 may be, for example, a general purpose personal computer with a related monitor. , a keyboard or other desired user interface. The actuators of the control force 1010A, 1010B, 1010C and 1010D can be any suitable control force controller as will be apparent to one skilled in the art upon review of the subject matter disclosed herein. For example, the actuators of the control force 1010A, 1010B, 1010C and 1010D can be pumps, electrodes, injectors, syringes or other such devices that can be used to force a material "through-through" a microfluidic device. The representative control forces themselves thus include capillary action, fluid flow controlled by a pump, fluid flow based on electrophoresis, fluid flow controlled by a pH gradient, or other fluid flow controlled by gradient. the scheme of Figure 10 the control force actuator 1010D is shown connected to an exit opening 810D, as will be described below, to demonstrate that at least a portion of the control force can be provided at the end point of the control force. desired flow of the solution, reagent and the like The collector 1020 was also provided to show that a reaction product 1048, as discussed below, can be collected in the end point of the system flow. In some embodiments, the manifold 1020 comprises a fluid reservoir. In some embodiments, the collector 1020 comprises a substrate. In some embodiments, the collector 1020 comprises the detector. In some embodiments, the manifold 1020 comprises a subject in need of therapeutic treatment. For convenience, the flow of the system is represented, generally in Figure 10 by the arrows Fl, F2 and F3. Continuing with reference to Figure 10 in some embodiments a chemical reaction is performed in the integrated flow system 1000. In some embodiments, the material 1040, for example, an active chemical, is introduced into the microfluidic device 1000 to through the opening 810A, while a second material 1042, for example, a second chemical reagent is introduced into the microfluidic device 1000, via the inlet opening 810B. The control force actuators 1010A and 1010B drive the chemical reagents 1040 and 1042 toward the microfluidic channels 831 and 833, respectively. The flow of chemical reagents 1040 and 1042 continues to the fluid reservoirs 850A and 850B, where a reservoir of reagent 1040 and 1042 is collected. The flow of chemical reagents 1040 and 1042 continues to the microfluidic channels 832 and 834 toward the point of intersection 860A where the initial contact between the chemical reagents 1040 and 1042 occurs. The flow of chemical reagents 1040 and 1042 then continues to the reaction chamber 870 where a chemical reaction of the chemical reagents 1040 and 1042 proceeds. Continuing with reference to Figure 10 , the reaction product 1044 flows to the microscopic scale channel 836 and to the intersection point 860B. The chemical reagent 1046 then reacts with the reaction product 1044 starting at the point of intersection 860B through the reaction chamber 838 and into the fluid reservoir 850C. A second reaction product 1048 is formed. The flow of the second reaction product 1048 continues through the "channel to" scale "microscopic-840 to" the opening 810D and finally to the collector 1020. Thus, it should be noted that the CPU 1002 drives the actuator of the control force 1010C so that the chemical reagent 1046 is released at the appropriate time to come into contact with the reaction product 1044 at the intersection point 860B. IV.D. Representative Applications of a Microfluidic Device Based on PFPE In some embodiments, the subject matter disclosed herein describes a method for selecting a sample by a characteristic. In some embodiments, the subject matter disclosed herein describes a method for distributing a material. In some embodiments, the subject matter disclosed herein describes a method for separating a material.

Accordingly, one skilled in the art will recognize that the PFPE-based microfluidic device described herein can be applied to many applications, including, but not limited to, genomic map tracing, fast separations, detectors, nanoscale reactions, printing by ink jet, drug or laboratory drug release on an integrated microcircuit, in vi tro diagnostics, injection nozzles, biological studies, high-throughput screening or separation technologies, for use in drug or drug recovery and materials science , diagnostic and therapeutic tools, research tools and - biological --- verification --- of food and natural resources, such as soil, water, and / or air samples collected with portable or stationary verification equipment. IV.D.l. Method for Selecting a Sample by a Feature In some embodiments, the subject matter disclosed herein discloses a method for selecting or separating a sample by a characteristic, the method comprising: (a) providing a microfluidic device comprising a structured layer of a photocured perfluoropolyether, wherein the structured layer of the light-cured perfluoropolyether comprises a plurality of channels; (b) provide a target or white material; (c) placing the sample in at least one of the plurality of channels; (d) contacting the sample with the target or target material; and (e) detecting an intersection between the sample and the target or target material, where the presence or absence of the interaction is indicative of the characteristic of the sample. Referring once again to Figure 10, at least one of the materials 1040 and 1042 comprises a sample. In some embodiments, at least one of the materials 1040 and 1042 comprises a target or white material. Thus, a "sample" generally refers to any material about which information related to a characteristic is desired. Also, a "target or target material" can refer to any material that can be used to provide information related to a characteristic of a sample based on an interaction between the target and target material and the sample. In some embodiments, for example, when the sample 1040 comes in contact with the target material 1042 an interaction occurs. In some embodiments, the interaction produces a reaction product 1044. In some embodiments, the interaction comprises a binding event. In some embodiments, the binding event comprises the interaction between, for example, an antibody and an antigen, a substrate and a ligand, or more particularly, a receptor and a ligand, or a catalyst and one or more chemical reagents. In some embodiments, the reaction product is detected by the detector 1030. In some embodiments, the method comprises placing the target material in at least one of the plurality of channels. Referring once again to Figure 10, in some embodiments, the target material comprises active material 880. In some embodiments, the target material comprises a substrate, eg, an unstructured NPL layer as shown in the Figures. 2A-2D. In some embodiments, the substrate comprises a semiconductor material. Referring now more particularly to Figures 2B-2D in some embodiments, at least one of the plurality of channels of the microfluidic device is in fluid communication with the substrate, for example, the unstructured layer NPL. In some embodiments, the target material is placed on a substrate, for example, the unstructured layer NPL. In some embodiments, at least one of the plurality of channels of the microfluidic device is in fluid communication with the target or target material placed on the substrate. In some embodiments, the method comprises placing a plurality of samples in at least one of the plurality of channels. In some modalities, the sample is selected from the group consisting of a therapeutic agent, a diagnostic agent, a research reagent, catalyst, a metal ligand, a non-biological organic material, an inorganic material, a food product, soil, water, and air. In some embodiments, the sample comprises one or more members of one or more libraries or chemical or biological compounds or components. In some embodiments, the sample comprises one or more of a nucleic acid template or template, a sequencing reagent, a primer, a primer extension product, a restriction enzyme, a PCR reagent, a PCR reaction product , or a combination thereof. In some embodiments, the sample comprises one or more of an antibody, a cellular receptor, an antigen, a receptor ligand, an enzyme, a substrate, an immunochemical, an immunoglobulin, a virus, a virus binding component, a protein, a cell factor, a growth factor, an inhibitor or a combination thereof. In some embodiments, the target or target material comprises one or more of an antigen, antibody, an enzyme, a reaction enzyme, a dye, a fluorescent dye, a sequencing reagent, a reagent PCR, a primer, a receptor, a ligand, a chemical reagent or a combination thereof. In some embodiments, the interaction comprises a joining event. In some embodiments, the detection of the interaction is effected by at least one or more of a spectrophotometer, a fluorometer, a photodiode, a multiplier tube, a microscope, a flashing counter, a camera, a CCD camera, film, a system of optical detection, a temperature detector, a conductivity meter, a potentiometer, an amperometric meter, a pH meter or a combination thereof. Accordingly, after a review of the present disclosure, one skilled in the art would recognize that the PFPE-based microfluidic device disclosed herein can be used in various selection or separation techniques, such as those described in U.S. Patent Nos. 6,749,814 de Bergh et al. , 6,737,026 to Bergh et al. , 6,630,353 to Parce et al. , 6,620,625 to Wolk et al, 6,558,944 to Parce et al, 6,547,941 to Kopf-Sill et al., 6,529,835 to Wada et al. , 6,495,369 from Kercso et al., And 6,150,180 from Parce et al. , each of which is incorporated here as a reference in its entirety. In addition, after a review of the description herein, one skilled in the art will recognize that the microfluidic device based on PFPE disclosed herein can be used, for example, to detect DNA, proteins, or other molecules associated with a system particular biochemist, as described in U.S. Patent No. 6,767,706 to Quake et al. , which is incorporated here as a reference in its entirety.

IV.D .2. Method for Distributing a Material In some embodiments, the subject matter disclosed herein discloses a method for distributing a material, the method comprising: (a) providing a microfluidic device comprising a structured layer of a light-cured perfluoropolyether, wherein the structured layer of the photocured perfluoropolyether comprises a plurality of channels, and wherein at least one of the plurality of channels comprises an exit opening; (b) providing at least one material; (c) placing at least one material in at least one of the plurality of channels, and (d) distributing at least one material through the exit opening, referring again to Figure 10, in some embodiments, a material, for example, a material 1040, the second material 1042, the chemical reagent 1046, the reaction product 1044 and / or the reaction product 1048 flows through the outlet port 810D and are placed in or on the collector 1020. In some embodiments, the material comprises a drug or drug In some embodiments, the method comprises dosing a predetermined dose of the drug or drug In some embodiments, the method comprises distributing the predetermined dose of drug or drug. the material comprises ink composition In some embodiments, the method comprises distributing the ink composition on a substrate In some embodiments, the distribution of the ink composition on a substrate or form a printed image. Accordingly, after a review of the present disclosure, one skilled in the art would recognize that the PFPE-based microfluidic device described herein can be used for microfluidic printing as described in U.S. Patent Nos. 6,334,676 to Kaszczuk et al. ., 6,128,022 of DeBoer et al. , and 6,091, 433 of Wen, each of which is incorporated herein by reference in its entirety. IV.D.3 Method for separating a material In some embodiments, the subject matter disclosed herein discloses a method for separating a material, the method comprising: (a) providing a microfluidic device comprising a structured layer of a light-cured perfluoropolyether, wherein the structure layer of the photocured perfluoropolyether comprises a plurality of channels, and wherein at least one of the plurality of channels comprises a separation region; (b) placing a mixture comprising at least one first material and a second material in the microfluidic device; (c) flowing the mixture in at least one of the plurality of channels comprising a separation region; (d) separating the first material from the second material in the separation region to form at least one separate material. Referring again to Figure 10, in some embodiments, at least one of the material 1040 and the second material 1042 comprises a mixture. For example, the material 1040, for example, a mixture flows through the microfluidic system into the chamber 870, which in some embodiments comprises a separation region. In some embodiments, the separation region comprises the active material 880, for example, a chromatographic material. The material 1040, e.g., a mixture, is separated in the chamber 870, e.g., a separation chamber, to form a third material 1044, e.g., a separate material. In some embodiments, the separated material 1044 is detected by the detector 1030. In some embodiments, the separation region comprises chromatographic immaterial. In some embodiments, the chromatographic material is selected from the group consisting of a size separation matrix, an affinity separation matrix; and a gel exclusion matrix, or a combination thereof. In some embodiments, the first and second material comprises one or more members of one or more libraries of chemical or biological compounds or components. In some embodiments, the first and second material comprises one or more of a nucleic acid pattern or model as a sequencing reagent, such as a primer, a primer extension product, a restriction enzyme, a PCR reagent, a PCR reaction product, or a combination thereof.

In some embodiments, the first and second material - - -comprises one or more -of an antibody, -like a cellular receptor . as an antigen, a ligand or receptor, an enzyme, a substrate, an immunochemical element, an immunoglobulin, an virus, a virus binding component, a protein, a cell factor, a growth factor, an inhibitor or a combination thereof. In some embodiments, the method comprises detecting a separate material. In some modalities, a detection of the separated material is effected by at least one or more of a spectrophotograph, a fluorometer, a photodiode, a photomultiplier tube, a microscope, a flashing counter, a camera, a CCD camera, a film, a system and optical detection, a temperature detector, a meter conductivity, a potentiometer, an amperometric meter, a pH meter or a combination thereof. Accordingly, after a review of the present disclosure, one skilled in the art would recognize that the microfluidic device based on PFPE that is described hereby can be used to separate materials, as described in U.S. Patent Nos. 6,752,922 of • Huang et al. , 6,274,089 to Chow et al. , and 6,444,461 to Knapp et al. , each of which is incorporated here as a reference in its entirety. 10 V. Examples The following Examples have been included for "- illustrate the modes of the subject matter disclosed herein Certain aspects of the following Examples are described in terms of techniques and procedures found or contemplated to work well in the practice of the subject matter revealed herein. In light of the present description and the general level of knowledge in the art, those experts can appreciate that the following examples are intended to be exemplary only and that they can be used numerous changes, modifications and alterations without departing from the scope of the subject matter disclosed herein. Example 1 Synthesis of Photocurated Functionalized PFPE Materials A representative reaction scheme for the synthesis and curing of a perfluoropolyether functionalized is given in reaction scheme 1.

Diagram of reaction 1. The Synthesis and Photocuring of Functional Perfluoropolyethers. This method is based on a previously reported procedure. See Priola, A., et al., Macromol. Chem. Phys. 1997, 198, 1893-1907. The reaction involves the functionalization of methacrylate of a commercially available PFPE diol ((Mn) 3800 g / mol) with isocyanatoethyl methacrylate. The subsequent photocuring of the material was carried out through the mixture with 1% p of 2,2-dimethoxy-2-phenylacetophenone and the exposure to UV radiation (? = 365 nm). Example 2 Materials Poly (tetrafluoroethylene oxide-difluoromethylene oxide) a, or diol, (ZDOL, average Mn 3,800 g / mol, 95% Aldrich Chemical Company, Milwaukee, Wisconsin, United States of America), methacrylate 2 -isocyanatoethyl (EIM, 99% Aldrich), 2,2-dimethoxy-2-phenyl acetophenone (DMPA, 99% Aldrich), Dibutyl tin diacetate (DBTDA, 99% Aldrich), and 1,1,2-trichlorotrifluoroethane (Freon) 113.99% Aldrich) were used as received. Example 3 Preparation of PFPE dimethacrylate (DMA) In a typical synthesis ZDOL (5.7227 g, 1.5 mmol) was added to a 50 mL spherical bottom flask and was tested with argon for 15 minutes. Then EIM (0.43 mL, 3.0 mmol) was added via a syringe together with Freon 113 _. { 2 mL), and DBTDA (50 μL). The solution was immersed in an oil bath and allowed to stir at 50 ° C for 24 h. The solution was then passed through a chromatographic column (alumina, Freon 113.2 cm x 5 cm). Evaporation of the solvent produced a clear, colorless, viscous oil, which was further purified by passing it through a 0.22-μm polyethersulfone filter. 1 H-NMR (ppm): 2.1, s (3H); 3.7, p (2H); 4.4, t (2H); 4.7, t (2H); 5.3, m (ÍH); 5.8, S (ÍH); 6.3, s (1 H). Example 4 Photocuration of the PFPE DMA In a typical cure 1% p DMPA (0. 05 g, 2.0 mmol) was added to the PFPE DMPA (5 -g, 1.2 mmol) together with 2 mL Freon 113 until a clear solution formed. After removal of the solvent, the cloudy viscous oil was passed through a 0.22 μm polyethersulfone filter to remove any DMPA that did not disperse in the PFPE DMPA. The filtered DMA PFPE was then irradiated with a UV source (UV Electro-lite curing chamber model No. 81432-ELC-500, Danbury, Connecticut, United States of America,? = 365 nm) while it was under an extension of nitrogen for 10 min, producing a clear, slightly yellow, rubbery material. Example 5 Fabrication of the Device with PFPE DMA In a typical fabrication, a photoinitiator containing PFPE DMA (as described in Example 4) was coated by centrifugation after a thickness of 20 μm (800 rpm) on an Si plate containing the desired photoprotective pattern. This was then placed in a UV curing chamber and irradiated for 6 s. Separately, a thick layer (~ 5 mm) of material was produced by pouring the photoinitiator containing PFPE DMA into a mold surrounding the Si layer containing the desired photoprotection pattern. This plate was irradiated with UV light for 1 min. After this step the thick layer was removed and entry holes were carefully punched in specific area of the device. The thick layer was then carefully placed over the top of the thin layer, so that the patterns in the two layers were precisely aligned and then the entire device was irradiated for 10 min. Once complete, the entire device was detached from the bale with both plates adhered together. Those curing times were determined as the optimal exposure times to achieve a good balance between the failure of the structure and the proper adhesion of the two layers. Example 6: Volume Up Experiments Volume up experiments were performed by dipping with fully cured PFPE DMA and fully cured Sylgard® 184 (Dow Corning, Midland, Michigan, USA).

United States) in dichloromethane. The% increase in volume was determined using the following equation:% volume increase = 100% * (Wt-W0) / W0 where Wt is the weight of the material immediately after immersion in dichloromethane during time t and dried with toilet paper and W0 is the original weight of the material. Example 7 Reagent The viscosities of the two elastomeric precursors (PFPE DMA and Sylgard® 184) were measured in a Rheometer of. TA Instruments AR2000 (New Castle, Delaware, United States of America). The measurements were taken on about 3-5 mL of material. The measurements on Sylgard® 184 precursors were taken immediately after mixing the two components. The cutting speed for Sylgard® 184 varied from 0.03 s "1 to 0.070 s" 1 and resulted in a constant viscosity at each cutting speed. The shear rate for the PFPE DMA varied from 0.28 s "1 to 34.74 s" 1 and also resulted in a constant viscosity regardless of the shear rate. Viscosities were obtained by taking an average of the viscosity values over all the shear speeds measured on a logarithmic graph. The untreated data for those experiments are shown in Figure 11. Example 8 Dynamic Mechanical Analysis (DMA) The module measurements were performed on a PerkinElmer Dynamic Mechanical Analyzer DMA 7e (Boston, Massachusetts, United States of America). Samples were cut into rectangles of 4 mm x 8 mm x 0.5 mm (width x length x thickness). The initial static force on each of the two samples was 5 mN and the load was increased at 500 mN / min until the sample broke or reached 6400 mN. The tensile modulus was obtained from the initial slope, (up to approximately a deformation of 20%) of the stress / strain curves.

Example 9 Dynamic Mechanical Thermal Analysis The thermal transitions of the two elastomers were obtained on a Seiko DMS 210 Dynamic Mechanical Thermal Analyzer (Seiko Instruments, Inc., Chiba, Japan). Samples were cut into rectangles of 4 mm x 20 mm x 0.5 mm (width x length x thickness). The following parameters were used: Lamp = 10, Voltage / Force of Compression = 10,000 g, Correction of Voltage / Compression = 1.2; Amplitude of force = 100. The sweep of temperature was -140 ° C to 50 ° C. The Tv were obtained from the temperature corresponding to the maximum in a graph of E "- (loss modulus) against the temperature Example 10 Measurements of the contact angle The static contact angles were measured using an Optical Contact Angle Meter of KSV Instruments CAM 200 (KSV Instruments, Ltd., Helsinki, Finland) Drops were placed on each of the fully cured elastomers using a syringe with a thread on top of 250 DL.Example 11 Results To measure the strength of the solvent, classic volumetric measurements were made using tests on both the crosslinked PFPE DMA and the Sylgard® 184, a PDMS Rubinstein, M., et al, Polymer Physics, Oxford University Press: New York, 2003; p 398. It was compared The weight of the sample before and after immersion in dichloromethane for several hours The data shows that after 94 h the PDMS network increased in volume to 109% by weight, while the PFPE network showed a negligible volume increase (< 3%) . PDMS and PFPE precursor materials and fully cured networks have similar processing and mechanical properties. The rheology experiments showed that the viscosity of the uncured PFPE DMA at 25 ° C is 0.36 Pa.s, which is significantly lower than that of 3.74 Pa.s for the uncured Sylgard® 184. Because both materials "are viscous oils at room temperature, however, methods of manufacturing the standard PDMS device with the PFPE materials could also be used." In other words, the PFPE materials of the subject matter disclosed herein They exhibit low viscosities and are fluid These properties distinguish PFPE materials from other fluoroelastomers, such as Kalrez® (DuPont Dow Elastomers, LLC, Wilmington, Delaware, United States of America) and Viton® (DuPont Dow Elastomers, LLC, Wilmington, Delaware, United States of America), which has high viscosities, for example, the viscosity of Viton® is 7800 Pa.s at 160 ° C. In addition, Kalrez® and Viton® are each cured only thermally. Mechanical dynamic (DMTA) was performed on fully cured materials, both PFPE and PDMS networks exhibited low temperature transitions (-112 ° C and -128 ° C, respectively) as it is evidenced by the maximum in the loss module E "(see Figure 12). This transition contributes to the similar elastic compartment of the two crosslinked materials at room temperature. The stress and strain analysis shows that the tensile modulus of the elastomer based on fully cured PFPE is 3.9 MPa, which is similar to that measured for the fully cured Sylgard® 184 (2.4 MPa). The measurements of the static contact angle were made in both elastomers. As provided in Table IV, the PFPE DMA elastomer showed a greater contact angle than Sylgard® 184 for water and methanol. Toluene and dichloromethane instantly increased the volume of Sylgard® 184 after contact, which prevented measurements from being made. The contact angle values for that solvent were obtained from the PFPE DMA material, however, when no increase in volume occurred. Table IV. Static Contact Angles (degrees) Elastomer Water Methanol Toluene Dichloromethane PFPE DMA 107 35 40 43 Sylgard® 184 101 22 a A (-) indicates that the solvent increased in volume and the material could not be accurately measured.

. In some embodiments, the fabrication of the device is effected according to the procedure illustrated in Figure 13. This procedure uses partial curing techniques to adhere the two layers without compromising characteristic sizes. Unger, M.A., et al., Science 2000, 288, 113-116. The PFPE DMA material was coated by centrifugation and molding using procedures designed for Sylgard® 184. To compare the solvent compatibility of the devices produced from the two materials, a dyed solution containing dichloromethane, acetonitrile and methanol was introduced. in one PFPE channel and one PDMS channel per capillary action (see Figure 14). The PFPE channels showed evidence of volume increase since the solution moved easily through the channel. A pronounced inverse meniscus was observed, indicating a good wetting behavior. In contrast, no solution came into the PDMS device because the channel was blocked when it made contact with the drops. As a control, a dyed methanol solution or a PDMS channel was easily introduced in the same manner. Valve actuation was effected by introducing pressurized air (-1.75 kgf / cm2 (25 psi)) into small holes that were drilled through the thick start layer of the channels. When the solution was present in the channel, the actuation of the valve was observed (see Figure 15). It will be understood that various details of the subject matter disclosed herein may be changed without departing from the scope of the subject matter disclosed herein. In addition, the foregoing description is for purposes of illustration only and not for purposes of limitation. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (171)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property. A method for forming a structured layer of a light-cured perfluoropolyether, characterized in that it comprises: (a) providing a substrate, wherein the substrate comprises a structured surface; (b) contacting a perfluoropolyether precursor with the structured surface of the substrate; and (c) photocuring the perfluoropolyether precursor to form a structured layer of a light-cured perfluoropolyether. The method according to claim 1, characterized in that it comprises: (a) coating a structured surface of the substrate with a mixture of a perfluoropolyether precursor and a photoinitiator to form a structured, coated substrate; (b) exposing the structured, coated substrate to ultraviolet radiation for a period of time to form a layer of a light-cured perfluoropolyether on the structured substrate; and (c) removing the light-cured perfluoropolyether layer from the structured substrate to produce a structured layer of the light-cured perfluoropolyether. 3. The method according to claim 2, characterized in that the perfluoropolyether precursor comprises a final functionalized perfluoropolyether. 4. The method according to claim 2, characterized in that the photoinitiator comprises 2,2-dimethoxy-2-phenyl acetophenone. The method according to claim 2, characterized in that the photocured perfluoropolyether comprises a perfluoropolyether dimethacrylate. 6. The method according to claim 2, characterized in that the light-cured perfluoropolyether comprises a perfluoropolyether diestiric. The method according to claim 2, characterized in that the structured substrate comprises a graded silicon plate. The method according to claim 2, characterized in that the structured substrate comprises a structured photoresist substrate. The method according to claim 2, characterized in that the step of coating comprises a step of coating by centrifugation. 10. The method according to claim 2, characterized in that the ultraviolet radiation has a wavelength of approximately 365 nanometers. The method according to claim 2, characterized in that the time period of the ultraviolet radiation ranges from about one second to about 300 seconds. 12. The method in accordance with the claim 11, characterized in that the time period of the ultraviolet radiation ranges from about one second to about 100 seconds. 13. The method according to the claim 12, characterized in that the time period of the ultraviolet radiation is about 60 seconds. The method according to claim 12, characterized in that the time period of the ultraviolet radiation is approximately 6 seconds. 15. The method according to claim 2, characterized in that the structured layer of the light-cured perfluoropolyether is between about 1 micrometer and about 100 micrometers thick. 16. The method according to claim 15, characterized in that the structured layer of the photocured perfluoropolyether is between about 1 micrometer and about 50 micrometer thick. 17. The method according to claim 16, characterized in that the structured layer of the light-cured perfluoropolyether is approximately 20 micrometers thick. 18. The method according to claim 2, characterized in that the structured layer of the light-cured perfluoropolyether is between about 0.1 millimeters and about 10 millimeters thick. The method according to claim 18, characterized in that the structured layer of the light-cured perfluoropolyether is approximately 5 millimeters thick. The method according to claim 1, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of channels on a microscopic scale. 21. The method according to the claim 20, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 22. The method of compliance with the claim 21, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 23. The method according to the claim 1, characterized in that it comprises forming a plurality of holes in the structured layer of the light-cured perfluoropolyether. 24. The method according to claim 23, characterized in that at least one of the plurality of orifices comprises an entrance opening. 25. The method of compliance with the claim 23, characterized in that at least one of the plurality of holes comprises an exit opening. 26. The method according to claim 23, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a channel on a microscopic scale; and (b) at least one of the plurality of holes. The method according to claim 2, characterized in that it comprises: (a) superposing a first structured layer of the light-cured perfluoropolyether on a second structured layer of the light-cured perfluoropolyether, wherein the patterns of the first and second layers of the light-cured perfluoropolyether are aligned a predetermined alignment; Y (b) exposing the first and second layers of the photocured perfluoropolyether to ultraviolet radiation for a period of time. 28. The method according to claim 27, characterized in that the first and second structured layers of the light-cured perfluoropolyether adhere to each other. 29. The method according to claim 27, characterized in that the first structured layer of the light-cured perfluoropolyether is approximately 5 millimeters thick. 30. The method according to claim 27, characterized in that the second structured layer of the light-cured perfluoropolyether is approximately 20 micrometers thick. 31. The method according to claim 27, characterized in that the predetermined alignment of the first and second layers of the light-cured perfluoropolyether forms a plurality of channels on a microscopic scale. 32. The method of compliance with the claim 31, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 33. The method according to claim 32, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 34. The method according to claim 27, characterized in that it comprises forming a plurality of holes in the first structured layer of the light-cured perfluoropolyether. 35. The method according to claim 34, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a channel on a microscopic scale; and (b) at least one of the plurality of holes. 36. A microfluidic device, characterized in that it is produced by the method according to claim 1. 37. A microfluidic device characterized in that it comprises a structured layer of a light-cured perfluoropolyether. 38. The microfluidic device according to claim 37, characterized in that the photocured perfluoropolyether is selected from one of a perfluoropolyether dimethacrylate and a perfluoropolyether diastiric, or a combination thereof. 39. The microfluidic device according to claim 37, characterized in that the structured layer of the photocured perfluoropolyether is between about 1 micrometer and about 100 micrometers thick. 40. The microfluidic device according to claim 39, characterized in that the structured layer of the photocured perfluoropolyether is approximately 20 micrometers thick. 41. The microfluidic device according to claim 37, characterized in that the structured layer of the light-cured perfluoropolyether is between about 0.1 millimeters and about 10 millimeters thick. 42. The microfluidic device according to claim 41, characterized in that the structured layer of the light-cured perfluoropolyether is approximately 5 millimeters thick. 43. The microfluidic device according to claim 37, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of channels on a microscopic scale. Four . The microfluidic device according to claim 43, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 45. The microfluidic device according to claim 44, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 46. The microfluidic device according to claim 37, characterized in that the structured layer of the light-cured perfluoropolyether comprises a plurality of holes. 47. The microfluidic device according to claim 46, characterized in that at least one of the plurality of orifices comprises an inlet opening. 48. The microfluidic device according to claim 46, characterized in that at least one of the plurality of orifices comprises an exit opening. 49. The microfluidic device according to claim 46, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a channel at a microscopic scale; and (b) at least one of the plurality of holes. 50. A microfluidic device, comprising a first structured layer of a light-cured perfluoropolyether and a second structured layer of a light-cured perfluoropolyether, characterized in that (a) the first structured layer of the light-cured perfluoropolyether is superimposed on the second structured layer of the light-cured perfluoropolyether; and (b) the patterns of the first and second layers of the light-cured perfluoropolyether are aligned in a predetermined alignment. 51. The microfluidic device according to claim 50, characterized in that the first and second structured layers of the light-cured perfluoropolyether adhere to each other. 52. The microfluidic device according to claim 50, characterized in that the first structured layer of the light-cured perfluoropolyether is approximately 5 millimeters thick. 53. The microfluidic device according to claim 50, characterized in that the second structured layer of the photocured perfluoropolyether is approximately 20 micrometers thick. 54. The microfluidic device according to claim 50, characterized in that the predetermined alignment of the first and second layers of the light-cured perfluoropolyether forms a plurality of channels on a microscopic scale. 55. The microfluidic device according to claim 54, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 56. The microfluidic device according to claim 55, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 57. The microfluidic device according to claim 50, characterized in that at least one of the structured layers of the photocured perfluoropolyether comprises a plurality of holes. 58. The microfluidic device according to claim 57, characterized in that at least one of the plurality of orifices comprises an inlet opening. 59. The microfluidic device according to claim 57, characterized in that at least one of the plurality of orifices comprises an exit opening. 60. The microfluidic device according to claim 57, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a channel on a microscopic scale; and (b) at least one of the plurality of holes. 61. A microfluidic device comprising a structured layer of a light-cured perfluoropolyether, characterized in that the structured layer of the light-cured perfluoropolyether comprises a solvent placed therein. 62. The microfluidic device according to claim 61, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of channels on a microscopic scale, and the solvent is placed in one or more of the channels. 63. The microfluidic device according to claim 62, characterized in that at least one of the microscopic-scale channels comprises a reservoir of fluid, and where the solvent is placed in the fluid reservoir. 64. The microfluidic device according to claim 62, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 65. The microfluidic device according to claim 64, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 66. The microfluidic device according to claim 61, characterized in that the structured layer of the light-cured perfluoropolyether comprises a plurality of holes. 67. The microfluidic device according to claim 66, characterized in that at least one of the plurality of orifices comprises an inlet opening. 68. The microfluidic device according to claim 66, characterized in that at least one of the plurality of orifices comprises an exit opening. 69. The microfluidic device according to claim 66, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a channel on a microscopic scale; and (b) at least one of the plurality of holes. 70. The microfluidic device according to claim 66, characterized in that one or more of the plurality of orifices is reversibly sealed. 71. The microfluidic device according to claim 61, characterized in that the solvent comprises an organic solvent. 72. A microfluidic device comprising a structured layer of a light-cured perfluoropolyether, characterized in that the structured layer of the light-cured perfluoropolyether comprises one or more chemical reagents placed therein. 73. The microfluidic device according to claim 72, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of channels on a microscopic scale, and where one or more chemical reagents is placed in one or more of the channels. 74. The microfluidic device according to claim 73, characterized in that at least one of the channels on a microscopic scale comprises a reservoir of fluid, and where one or more chemical reagents is placed in the fluid reservoir. 75. The microfluidic device according to claim 74, characterized in that at least one of the channels on a microscopic scale comprises a reaction chamber in fluidic communication with the fluid reservoir, and wherein one or more chemical reagents is placed in the chamber of the fluid reservoir. reaction. 76. The microfluidic device according to claim 73, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 77. The microfluidic device according to claim 76, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 78. The microfluidic device according to claim 72, characterized in that the structured layer of the light-cured perfluoropolyether comprises a plurality of holes. 79. The microfluidic device according to claim 78, characterized in that at least one of the plurality of orifices comprises an entrance opening. 80. The microfluidic device according to claim 78, characterized in that at least one of the plurality of orifices comprises an exit opening. 81. The microfluidic device according to claim 78, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a channel on a microscopic scale; and (b) at least one of the plurality of holes. 82. The microfluidic device according to claim 78, characterized in that one or more of the plurality of orifices is reversibly sealed. 83. A microfluidic device comprising a structured layer of a light-cured perfluoropolyether, characterized in that the structured layer of the light-cured perfluoropolyether comprises one or more reaction products placed therein. 84. The microfluidic device according to claim 83, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of channels on a microscopic scale, and where one or more reaction products is placed in one or more of the channels. 85. The microfluidic device according to claim 84, characterized in that at least one of the channels on a microscopic scale comprises a reaction chamber, and where one or more reaction products is placed in the reaction chamber. 86. The microfluidic device according to claim 85, characterized in that at least one of the channels on a microscopic scale comprises a reservoir of fluid in fluidic communication with the reaction chamber, and where one or more reaction products is placed in the chamber of reaction. 87. The microfluidic device according to claim 84, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 88. The microfluidic device according to claim 87, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 89. The microfluidic device according to claim 83, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of holes. 90. The microfluidic device according to claim 89, characterized in that at least one of the plurality of orifices comprises an inlet opening. 91. The microfluidic device according to claim 89, characterized in that at least one of the plurality of orifices comprises an exit opening. 92. The microfluidic device according to claim 89, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a microscopic-scale channel; and (b) at least one of the plurality of holes. 93. The microfluidic device according to claim 89, characterized in that one or more of the plurality of orifices is reversibly sealed. 94. A microfluidic device comprising a structured layer of a light-cured perfluoropolyether, characterized in that the structured layer of the light-cured perfluoropolyether comprises one or more chemical reagents and one or more reaction products placed therein. 95. The microfluidic device according to claim 94, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of channels on a microscopic scale, and one or more chemical reagents and one or more reaction products are placed in one or more of the channels. 96. The microfluidic device according to claim 95, characterized in that at least one of the microscopic-scale channels comprises a first fluid reservoir, and where one or more chemical reagents are placed in the first fluid reservoir. 97. The microfluidic device according to claim 96, characterized in that at least one of the channels on a microscopic scale comprises a reaction chamber in fluidic communication with the fluid reservoir, and wherein one or more chemical reagents and one or more products of reaction are placed in the reaction chamber. 98. The microfluidic device according to claim 97, characterized in that at least one of the channels on a microscopic scale comprises a second fluid reservoir in fluidic communication with the reaction chamber, and wherein one or more reaction products is placed in the reservoir. second reservoir of fluid. 99. The microfluidic device according to claim 95, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 100. The microfluidic device according to claim 99, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 101. The microfluidic device according to claim 95, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of holes. 102. The microfluidic device according to claim 101, characterized in that at least one of the plurality of orifices comprises an inlet opening. 103. The microfluidic device according to claim 101, characterized in that at least one of the plurality of orifices comprises an exit opening. 104. The microfluidic device according to claim 101, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a channel on a microscopic scale; and (b) at least one of the plurality of holes. 105. The microfluidic device according to claim 101, characterized in that one or more of the plurality of orifices is reversibly sealed. 106. A method for flowing a material in a microfluidic device, characterized in that it comprises: (a) providing a microfluidic device comprising at least one structured layer of a light-cured perfluoropolyether, wherein the structured layer of the light-cured perfluoropolyether comprises at least one channel microscopic scale; and (b) flowing a material in the channel at a microscopic scale. 107. The method of compliance with the claim 106, characterized in that it comprises placing a material in the microfluidic device. 108. The method according to claim 106, characterized in that it comprises applying a control force to move the material along the channel on a microscopic scale. 109. The method according to claim 106, characterized in that it also comprises a plurality of channels on a microscopic scale. 110. The method of compliance with the claim 109, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 111. The method according to claim 110, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 112. The method according to claim 106, characterized in that the structured layer of the light-cured perfluoropolyether comprises a plurality of holes. 113. The method according to claim 112, characterized in that at least one of the plurality of orifices comprises an entrance opening. 114. The method according to claim 112, characterized in that at least one of the plurality of orifices comprises an exit opening. 115. The method according to claim 112, comprising at least one pressure-operated valve, characterized in that the pressure-operated valve is defined by one of: (a) a channel on a microscopic scale; and (b) at least one of the plurality of holes. 116. The method of compliance with the claim 115, characterized in that the pressure operated valve is operated by introducing a pressurized fluid into one of: (a) a channel on a microscopic scale; and (b) at least one of the plurality of holes. 117. The method of compliance with the claim 116, characterized in that the pressurized fluid has a pressure of between about 0.7031 kgf / cm2 (10 psi) and about 2.8124 kgf / cm2 (40 psi). 118. The method of compliance with the claim 117, characterized in that the pressure is about 1.75775 kgf / cm2 (25 psi). 119. The method of compliance with the claim 106, characterized in that the material comprises a fluid. 120. The method according to claim 119, characterized in that the fluid comprises a solvent. 121. The method according to claim 120, characterized in that the solvent comprises an organic solvent. 122. The method according to claim 106, characterized in that the material flows in a predetermined direction along the channel at a microscopic scale. 123. A method for effecting at least one chemical reaction, the method is characterized in that it comprises: (a) providing a microfluidic device comprising a structured layer of a light-cured perfluoropolyether; and (b) contacting a first reagent and a second reagent in the microfluidic device to form at least one reaction product. 124. The method of compliance with the claim 123, characterized in that the structured layer of the photocured perfluoropolyether comprises a plurality of channels on a microscopic scale. 125. The method of compliance with the claim 124, characterized in that at least one of the microscopic-scale channels comprises a fluid reservoir. 126. The method of compliance with the claim 125, characterized in that at least one of the channels on a microscopic scale comprises a fluid reaction chamber in fluidic communication with the fluid reservoir. 127. The method according to claim 124, characterized in that the plurality of channels on a microscopic scale comprises an integrated network of channels on a microscopic scale. 128. The method according to claim 127, characterized in that the microscopic-scale channels of the integrated network intersect at predetermined points. 129. The method according to claim 123, characterized in that the first reagent and the second reagent are placed in • separate channels of the microfluidic device. 130. The method of compliance with the claim 123, characterized in that it comprises flowing the first reagent and the second reagent in a predetermined direction in the microfluidic device. 131. The method according to claim 123, characterized in that the contact of the first reagent and the second reagent is carried out in a reaction chamber on a microscopic scale. 132. The method according to claim 123, characterized in that it comprises flowing the reaction product in a predetermined direction in the microfluidic device. 133. The method according to claim 123, characterized in that it comprises recovering the reaction product. 134. The method of compliance with the claim 133, characterized in that it comprises flowing the reaction product to an outlet opening of the microfluidic device. 135. The method according to claim 123, characterized in that it comprises contacting the reaction product with a third reagent to form a second reaction product. 136. The method according to claim 123, characterized in that the first reagent and the second reagent comprise an organic solvent. 137. The method according to claim 123, characterized in that the chemical reaction comprises a chemical reaction at nanometric scale. 138. A reaction product, characterized in that it is formed by the method according to the claim 123. 139. The method according to claim 123, characterized in that the first reagent and the second reagent are independently selected from one of a nucleotide and a polynucleotide. 140. The method according to claim 139, characterized in that the reaction product comprises a polynucleotide. 141. The method according to claim 140, characterized in that the polynucleotide is DNA. 142. A reaction product, characterized in that it is formed by the method according to claim 139. 143. A method for separating a sample by a characteristic, characterized in that it comprises: (a) providing a microfluidic device comprising a structured layer of a light-cured perfluoropolyether, wherein the structured layer of the photocured perfluoropolyether comprises a plurality of channels; (b) provide a target or white material; (c) placing the sample in at least one of the plurality of channels; (d) contacting the sample with the target or target material; and (e) detecting an interaction between the sample and the target or target material, where the presence or absence of the interaction is indicative of the characteristic of the sample. 144. The method according to claim 143, characterized in that it comprises placing the target or target material in at least one of the plurality of channels. 145. The method according to claim 143, characterized in that the target material comprises a substrate. 146. The method of compliance with the claim 145, characterized in that at least one of the plurality of channels of the microfluidic device is in fluid communication with the substrate. 147. The method according to claim 143, characterized in that the target material is placed on a substrate. 148. The method according to claim 147, characterized in that at least one of the plurality of channels of the microfluidic device is in fluid communication with the target material placed on the substrate. 149. The method according to claim 143, characterized in that it comprises placing a plurality of samples in at least one of the plurality of channels. 150. The method of compliance with the claim 143, characterized in that the sample is selected from the group consisting of a therapeutic agent, a diagnostic agent, a research reagent, a catalyst, a metal ligand, a non-biological organic material, an inorganic material, a food product, soil , water, and air. 151. The method according to claim 143, characterized in that the sample comprises one or more members of one or more libraries of chemical or biological compounds or components. 152. The method according to claim 143, characterized in that the sample comprises one or more of a nucleic acid template or pattern, a sequencing reagent, a primer, a primer extension product, a restriction enzyme, a PCR reagent, a PCR reaction product, or a combination thereof. 153. The method according to claim 143, characterized in that the sample comprises one or more of an antibody, a cellular receptor, an antigen, a ligand receptor, an enzyme, a substrate, an immunochemical element, an immunoglobulin, a virus , a virus binding component, a protein, a cell factor, a growth factor, an inhibitor, or a combination thereof. 154. The method according to claim 143, characterized in that the target material comprises one or more of an antigen, antibody, an enzyme, a restriction enzyme, a dye, a fluorescent dye, a sequencing reagent, a reagent of PCR, a primer, a receptor, a ligand, a chemical reagent, or a combination thereof. 155. The method according to claim 143, characterized in that the interaction comprises a joining event. 156. The method according to claim 143, characterized in that the detection of the interaction is effected by at least one or more of a spectrophotometer, a fluorometer, a photodiode, a photomultiplier tube, a microscope, a flashing counter, a camera , a CCD camera, film, an optical detection system, a temperature detector, a conductivity meter, a potentiometer, an amperometric meter, a pH meter, or a combination thereof. 157. A method for distributing a material, the method is characterized in that it comprises: (a) providing a microfluidic device characterized in that it comprises a structured layer of a light-cured perfluoropolyether, wherein the structured layer of the photocured perfluoropolyether comprises a plurality of channels, and wherein minus one of the plurality of channels comprises an exit opening; (b) providing at least one material; (c) placing at least one material in at least one of the plurality of channels; and (d) distributing at least one material through the exit opening. 158. The method according to claim 157, characterized in that the material comprises a drug or drug. 159. The method according to claim 158, characterized in that it comprises dosing a predetermined dose of the drug or drug. 160. The method according to claim 159, characterized in that it comprises distributing the predetermined dose of the drug or drug. 161. The method according to claim 157, characterized in that the material comprises an ink composition. 162. The method of compliance with the claim 161, characterized in that it comprises distributing the ink composition on a substrate. 163. The method of compliance with the claim 162, characterized in that the distribution of the ink composition on a substrate forms a printed image. 164. A method for separating a material, the method is characterized in that it comprises: (a) providing a microfluidic device comprising a structured layer of a light-cured perfluoropolyether, wherein the structured layer of the light-cured perfluoropolyether comprises a plurality of channels, and where at least one of the plurality of channels comprises a separation region; (b) placing a mixture comprising at least one first material "and a second material in the microfluidic device; (c) flowing the mixture toward at least one of the plurality of channels comprising a separation region; and (d) separating the first material from the second material in the separation region to form at least one separate material. 165. The method according to claim 164, characterized in that the separation region comprises a chromatographic material. 166. The method according to claim 165, characterized in that the chromatographic material is selected from the group consisting of a size separation matrix, an affinity separation matrix; and a gel exclusion matrix, or a combination thereof. 167. The method of compliance with the claim 164, characterized in that the first or second material comprises one or more members of one or more libraries of chemical or biological compounds or components. 168. The method according to claim 164, characterized in that the first or second material comprises one or more of a nucleic acid template or pattern, a sequencing reagent, a primer, a primer extension product, a restriction enzyme , a PCR reagent, a PCR reaction product or a combination thereof. 169. The method according to claim 164, characterized in that the first or second material comprises one or more of an antibody, a cellular receptor, an antigen, a ligand receptor, an enzyme, a substrate, an immunochemical element, an immunoglobulin , a virus, a virus binding component, a protein, a cell factor, a growth factor, an inhibitor, or a combination thereof. 170. The method according to claim 164, characterized in that it comprises detecting the separated material. 171. The method according to claim 170, characterized in that the detection of the separated material is carried out by at least one or more of a spectrophotometer, a fluorometer, a photodiode, a photomultiplier tube, a microscope, a flashing counter, a camera , a CCD camera, film, an optical detection system, a temperature detector, a conductivity meter, a potentiometer, an amperometric meter, a pH meter or a combination thereof. SUMMARY OF THE INVENTION A photocurable perfluoropolyether functionalized as a material to make a solvent-resistant microfluidic device is used. These solvent-resistant microfluidic devices can be used to control the flow of small amounts of a fluid, such as an organic solvent, and to perform chemical reactions on a microscopic scale that are not sensitive to other microfluidic devices based on polymers. 2/15 m.2D