CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to and the benefit of U.S. Provisional Application No. 61/383,102, filed on September 15, 2010, the entire contents of which are hereby incorporated herein by reference.

TECHNICAL FIELD

[0002] This invention relates generally to small, reliable check valves and methods of manufacturing same.

BACKGROUND

[0003] The need for ever-smaller pumping devices, particularly in the medical field, continues to grow. As a result, the need for increasingly small operational pump components, such as check valves, is growing as well, challenging the limits of conventional manufacturing processes. Valves less than 1 or 2 mm in size are difficult to fabricate using conventional molding technology, and while some fabrication of micro-scale valves using

microelectromechanical systems (MEMS) technology is being performed, such techniques can be expensive. Small, commercially available silicone valves produced using conventional techniques tend to be unreliable (exhibiting leakage and large production variations) at the sub- millimeter scale. A clear need exists for a small, reliable and durable valve that is simple to fabricate and suitable for use in micro-scale pumps having submillimeter component dimensions.

SUMMARY

[0004] In various embodiments, the present invention provides elastomeric check valve structures that can be manufactured reliably and cost-effectively at small (e.g., submillimeter) scales. A check valve is a one-way valve that allows free flow when a positive differential pressure is applied across the valve (i.e., the pressure at the inlet is greater than the pressure at the outlet), but inhibits (or "checks") backflow when a negative differential pressure is applied. As described herein, the check valve may be molded from an elastomeric polymer, and may have a configuration similar to a duckbill valve, with an outlet slit that closes in the absence of a positive pressure differential. [0005] In one aspect, the invention is directed to a check valve including an elongated, elastomeric body shaped to fit within a tube and having two axially opposed ends. In various embodiments, a pocket extends into the body from an opening in the first end and has a tapered (and, optionally, rounded) terminus within the body. A slit extends from the second end of the body to the pocket terminus to fluidically couple the second end to the pocket. The slit can be opened only by positive fluid pressure within the pocket. The slit may be sized so as to provide a specified stiction area, and may be tapered from a wide end at the second body end to a narrow end at the pocket terminus.

[0006] The valve body may be formed of a material including or consisting essentially of medical-grade silicone, silicone rubber, or a polyurethane -based elastomeric composite, or any material with suitable durometer (e.g., a durometer in the range from about Shore A 5 to about Shore A 100, preferably in the range from about Shore A 20 to about Shore A 40). In some embodiments, the length of the body does not exceed 1 mm and/or the diameter of the body does not exceed 0.5 mm.

[0007] In another aspect, the invention relates to a check valve assembly including a valve as described above, a first tube tightly surrounding a portion of the body and extending past the first end from an intermediate point between the first and second ends of the body distal to the pocket terminus, and a second tube tightly surrounding at least a portion of the first tube and extending past the second end of the body. The diameter of the second tube exceeds the diameter of the body so as not to interfere with opening of the slit. In some embodiments, the elastomeric body is made of (or includes) silicone, and the tubes are made of (or include) parylene.

[0008] In yet another aspect, the invention pertains to a method of manufacturing a check valve (such as the check valve described above). In various embodiments, the method includes molding an elongated valve body having first and second axially opposed ends and defining therein a pocket extending from an opening in the first end to a tapered terminus within the body. Further, the method involves forming a slit in the body extending from the second end to the pocket terminus to fluidically couple the second end to the pocket portion. The slit is openable only by positive fluid pressure within the pocket portion. The slit may be cut with, for example, a micrometer-scale blade, a silicon blade, a water jet, a laser, a needle, or a fine probe. [0009] In some embodiments, the valve body is molded by filling a glass capillary with an uncured elastomeric polymer in liquid form, introducing an air bubble into the uncured polymer, curing the polymer so as to retain the air pocket following cure, removing the cured polymer from the capillary, and cutting a length of the removed polymer such that the cut length contains a portion of the air pocket that includes the terminus. In alternative embodiments, the molding step involves providing two mold forms, the first form including a cavity that defines an exterior surface of the valve body, and the second form including an extruded structure that defines the pocket and can be inserted into the cavity. Using the two mold forms, the valve body may be molded by filling the space within the cavity surrounding the extrusion with elastomeric polymer in liquid form, curing the polymer, and removing the cured polymer from the mold forms. The mold form may be manufacture using microphotolithography, precision machining, deposition, or a combination of these techniques.

[0010] A further aspect relates to a method of manufacturing a check valve assembly. In various embodiments, the method includes the steps of bonding a first tube to a fixture; placing a valve body as described above into the first tube; forming a slit extending from the second end to the pocket terminus to fluidically couple the second end to the pocket portion; bonding a second tube to the first tube; and removing an assembly comprising the valve body, the second tube, and a portion of the first tube from the fixture. The bonding steps may include applying epoxy between respective bonded surfaces. A stainless-steel needle may be used as the fixture; in some embodiments, the needle is crimped at the tip and the first tube bonded to the crimped portion.

[0011] These and other advantages and features of the invention will become more apparent through reference to the following description, the accompanying drawings, and the claims. Furthermore, it is to be understood that the features of the various embodiments described herein are not mutually exclusive and can exist in various combinations and permutations. As used herein, the terms "substantially" and "about" generally mean ±10%, and, in some embodiments, ±5%. The term "consists essentially of means excluding other materials that contribute to function, unless otherwise defined herein. Nonetheless, such other materials may be present, collectively or individually, in trace amounts. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 graphically illustrates the flow/pressure curve of a typical one-way valve;

[0013] FIG. 2 is a schematic sectional drawing of an elastomeric check valve structure in accordance with one embodiment;

[0014] FIGS. 3A-3D are schematic sectional drawings illustrating the function of elastomeric check valves in accordance with various embodiments;

[0015] FIGS. 4 A and 4B are schematic sectional drawings illustrating different shapes of the valve body in accordance with two embodiments;

[0016] FIGS. 5A and 5B are perspective drawings of a valve body in accordance with two embodiments, illustrating valve slits with small and large surface area, respectively;

[0017] FIGS. 6A-6E are schematic sectional drawings illustrating a method of

manufacturing an elastomeric valve body in a glass capillary in accordance with one embodiment;

[0018] FIGS. 7A-7C are schematic sectional drawings illustrating a soft-lithography method for manufacturing an elastomeric valve body in accordance with one embodiment;

[0019] FIG. 8 is a schematic sectional drawing illustrating a deposition method of manufacturing an elastomeric valve body in accordance with one embodiment;

[0020] FIGS. 9A-9E are schematic sectional drawings illustrating a method of assembling an elastomeric check valve in accordance with one embodiment;

[0021] FIG. 10 graphically depicts an experimentally determined flow/pressure curve of an elastomeric check valve in accordance with on embodiment;

[0022] FIG. 11 A is a perspective drawing illustrating a pump device including an elastomeric check valve in accordance with one embodiment; and

[0023] FIGS. 1 IB and 11C are sectional drawings illustrating the dimension of a check valve suitable for use in the pump device of FIG. 11A. DETAILED DESCRIPTION

[0024] FIG. 1 shows a typical flow/pressure curve of a normally-closed one-way valve (i.e., the flow rate through the valve plotted as a function of differential pressure across the valve), which conceptually illustrates the performance characteristic of the valve. When pressure increases in the positive pressure direction, as indicated by the dashed line, the valve does not open (and the flow rate, thus, remains zero) until the "cracking pressure" is reached. After passing the cracking pressure, the flow rate increases with pressure. When the pressure subsequently decreases, as indicated by the solid line, the flow rate drops to zero at a pressure less than or equal to the cracking pressure, which is referred to as the "closing pressure." As the pressure becomes negative, no flow can be observed until the "breakdown pressure" is reached, at which point the integrity of the valve structure is damaged and the fluid flows in the backward direction.

[0025] FIG. 2 illustrates a check valve 200 in accordance with various embodiments, which can, generally, achieve the flow-pressure characteristic described above. The valve 200 includes an elongated valve body 202 forming a pocket 204 therein. The pocket 204 extends from an opening 205 at the inlet end 206 of the valve body 202 to a terminus 208 within the body 202. A slit 210 connects the pocket terminus 208 to the outlet end 212 of the body 202. Positive fluid pressure in the pocket 204 causes the slit 210 to open. The pocket 204 is desirably tapered towards the terminus 208 so as to direct fluid that enters the pocket 204 through the opening 205 towards the slit 210. For example, the pocket may have a "bullet-like" shape, as shown in FIG. 2, or a frustoconical shape.

[0026] The valve body 202 may be made of an elastomeric polymer (or "elastomer") of suitable durometer values (e.g., a durometer value in the range from about Shore A 5 to about Shore A 100, in some embodiments in the range from about Shore A 20 to about Shore A 40). The durometer is a standard measure of the hardness of a rubber-like material, and may be determined, for example, by measuring the depth of an indentation created in the material surface by a standard force. The durometer value influences both the elasticity and the surface energy (due to stiction) of the elastomer material. Within typical durometer ranges of rubber materials, a higher-durometer elastomer is usually softer (i.e., has lower elasticity) and

"stickier" (i.e., has higher stiction). In valve structures, both higher elasticity and higher stiction tend to result in higher cracking pressures. Suitable elastomers for use in valves described herein include, for example, medical-grade silicone, silicone rubber, and polyurethane, but other natural or synthetic rubbers (like buna (polybutadiene) or viton

(fluorinated hydrocarbon)) may also be used

[0027] The valve body 202 may be housed within a tube for protection. To minimize the outside diameter of the overall structure, the housing tube preferably has a thin wall. The tube may be made from a material that resists expansion, thereby containing the valve's internal pressure; suitable materials include, e.g., hard plastics (such as, but not limited to, parylene, polystyrene, polyacrylate, or polyetherehterketone), metals, glass, or composite materials. The valve housing desirably conforms tightly to the maximum dimension of the valve body 202 at the inlet 206, but provides a circumferential clearance around the front section of the valve that includes the outlet 212. As illustrated, this may be accomplished with two nested tubes 216, 218. A portion of the valve body 202 that includes the inlet end 206 may be mounted or received within the inner, upstream tube 216, which is itself received within the outer, downstream tube 218 as illustrated. The two tubes 216, 218 may be secured to one another where they overlap with an adhesive such as, e.g., epoxy. In alternative embodiments, the valve body may be placed into a single tube of varying diameter, or it may include a recessed portion at the outlet end and be placed into a single tube of constant diameter.

[0028] FIGS. 3A-3D illustrate the operation of the valve 200. The slit 210 is normally closed (FIG. 3A). When fluidic pressure exceeding the cracking pressure is applied in the forward direction, the valve slit 210 is forced open, and fluid flows through the valve (FIG 3B). When the pressure is relieved, the valve slit 210 closes (FIG. 3C); in general, the closing pressure of the valve is greater than zero. As pressure is applied in the backward direction, the slit 210 remains closed, up to a breakdown pressure, due to stiction (i.e., static-friction) forces at the slit interface, thereby preventing backflow (FIG. 3D).

[0029] The pressure exerted on the walls of the valve body closest to the valve outlet 212 creates peeling forces at the slit 210, which may affect valve opening both under forward pressure and under backpressure. By using a valve body 202 whose side walls remain parallel near the outlet 212 (resulting, e.g., in a constant diameter for a circular valve cross section), as shown in FIG. 4A, or are sloped towards the outlet 212 (resulting in a decreasing diameter for a circular cross section), as shown in FIG. 4B, the peeling forces under backpressure may be minimized (and the breakdown pressure, thus, maximized). [0030] The closure behavior of the valve (as characterized, among other things, by the cracking and closing pressures) generally depends on the elasticity and geometry of the valve body 202 as well as on the surface energy of the slit 210. The surface energy, in turn, is a function of the area of the stiction surface (i.e., the area of the slit) and the coefficient of static friction of the valve body material. Thus, for a given valve material, the cracking pressure of the valve may be set by adjusting the stiction area. The larger the stiction area, the higher the surface energy and, thus, the cracking pressure. As shown in FIGS. 5A and 5B, the stiction area can be increased, for example, by increasing the length of the valve body 202 while keeping the length of the pocket 204 constant. The cracking pressure also depends on the durometer, which affects both the elasticity of the valve body 202 and stiction of the slit 210. Materials with lower durometer are typically more elastic, which tends to decrease the cracking pressure, but also have higher surface energy, which tends to increase the cracking pressure. To the extent important to a particular application, the relative influence of elasticity and stiction can be readily determined without undue experimentation, and if desired, a suitable material for a target application and cracking pressure can be based thereon.

[0031] An exemplary check valve in accordance herewith may include a silicone valve body housed in parylene tubing. Parylene is highly biocompatible and, thus, particularly suited for use in medical implants. To facilitate use of the valve in microscale pumps, the valve body may be fabricated to a diameter of less than 0.5 mm (e.g., 0.25 mm) and a length of less than 1 mm (e.g., 0.5 mm); in some embodiments, even valve dimensions of only tens of micrometers are possible. However, larger valves are also within the scope of the invention.

[0032] Elastomeric valve bodies as described herein can be manufactured at low cost using any of various molding techniques. One method, illustrated in FIGS. 6A-6E, utilizes a glass pipette as the mold form, into which an isolated air pocket is introduced. In a first step, shown in FIG. 6A, the interior surface of a glass micropipette 600 is coated with polyvinyl alcohol

(PVA), for example, by filling the micropipette 600 with liquid PVA solution (e.g., lg of PVA dissolved in 20 mL de-ionized water) using a syringe, blow-drying the PVA from inside the glass pipette 600 to form a thin PVA layer 602, and baking the pipette 600 in an oven at 80 °C ±5 °C for about one hour. Next, a silicone mixture 604, such as, e.g., NuSil MED4-4210 (available from NuSil Silicone Technology, Carpinteria, California), is injected into the PVA- coated pipette (FIG. 6B). One or more air bubbles 606 are then deliberately introduced into the silicon-filled glass pipette 600 before the silicone 604 is cured in an oven at 80 °C ±5 °C for about 1.5 hours (FIG. 6C). The PVA layer 602 may subsequently be dissolved, e.g., by soaking the micropipette 600 for about twelve hours in de-ionized water, so as to release the cured silicone 604 from the pipette 600 (FIG. 6D). Finally, the silicone block may be cut along sections near and through the enclosed air bubble 606 to obtain the valve body 608 (FIG. 6E).

[0033] Other suitable molding techniques for the valve body include the use of

microphotolithography to fabricate suitable mold forms, followed by soft lithography to mold the valve body. For example, silicon blocks may be etched using photoresist as a mask to create two complementary mold forms as illustrated in FIG. 7A: an exterior form 700 that includes a cylindrical or cuboid cavity 702 defining the outer surface of the valve body, and an insert 704 with an extruded structure 706 that defines the pocket 708. Suitable etching techniques for producing the molds 700, 702 include (but are not limited to) wet etching (using, e.g., acid, alkali, or mixing chemicals), dry etching (e.g., plasma etching, reactive ion etching (RIE), and deep reactive ion etching (DRIE)), and irradiation etching (using high-energy radiation such as UV-light, X-rays (LIGA), or gamma rays). To produce the valve body, liquid-phase elastomer 710 is injected into the two-part mold 700,702 (FIG. 7B), cured, and then released from the mold (FIG. 7C) according to procedures well-known in the art.

[0034] The use of photolithography to pattern the molds 700, 702 generally offers finer control over feature sizes and shapes than standard machining processes. However, in various embodiments, traditional or non-traditional high-precision machining techniques may be used to produce the molds for the valve body. For example, electrical discharge machining (EMD) may be utilized to create highly accurate metal molds for the valve. Yet another way to create the insert mold 702 for the elastomeric check valve body is to use a deposition technique.

Examples include, but are not limited to, thick photoresist coating (using, e.g., AZ 4610, AZ 9260, or SU-8 series photoresist), oxide deposition, and metal deposition. FIG. 8 illustrates the use of a mold created by a deposition technique. The extruded structure 800 may be made by first depositing a thick layer of photoresist (or another suitable material), and then controllably removing the material (for example, using developer to remove photoresist that has been exposed to UV radiation) to leave the desired structure. [0035] FIGS. 9A-9F illustrate a procedure for assembling the valve structure. In a first step, shown in FIG. 9A, a suitable fixture 900 for holding the device during the assembly process is provided. The fixture 900 may, for example, be a stainless steel needle 900 (e.g., a 23G needle), which, if its size and shape so require, may be crimped to create a flat, recessed tip. The flat, recessed end of an upstream parylene tube 902 is slipped onto and bonded to the fixture 900 (e.g., onto its flat, recessed tip). Bonding may be accomplished, for example, by applying epoxy (or another suitable adhesive) 904 around the edge of the parylene tube 902, allowing to run into the gap between the parylene tube 902 and the fixture 900, and curing it in an oven at about 80 °C for 180 ±10 minutes. Next, a previously formed valve body 906 is placed into and bonded to the parylene tube 902 (FIG. 9B). For example, silicone 908 may be mixed and applied to the internal surface of the round portion 910 of the parylene tube, and, after placement of a silicone valve body 906 into the tube, cured at 80 ±5 °C for 100 ±10 min.

[0036] A symmetrically shaped, micrometer-scale blade (e.g., an ophthalmic blade or lance) may be used to cut a slit 91 1 into the silicone valve body 906 at the outlet end (FIG. 9C), resulting in a clean interface. Alternative precise cutting methods include, but are not limited to, use of a silicon blade, water jet, laser, needle, or fine probe. Depending on the cutting tool used, the shape of the slip may vary. For example, a spear-type blade typically results in a slit that is tapered towards the terminus of the pocket, as illustrated in FIGS. 5A and 5B. Other tools may cause the slit to be straight or tapered towards the outlet end, or take the shape of a narrow strip or line.

[0037] In the next step, a downstream parylene tube 912 is slipped over the round portion 910 of the upstream tube 902. Epoxy (or another suitable adhesive) 914 is applied around the interface between the upstream and downstream parylene tubes 902, 912 and allowed to run into the gap between both tubes (FIG. 9D). The epoxy may be cured in an oven programmed with the following cycle: (1) temperature ramping to 80 °C over a period of thirty minutes; (2) soak at 80 °C for 180 minutes; and (3) temperature ramping to 20°C over a period of one minute. Finally, the completed valve structure is cut off the fixture 900 using, e.g., a scalpel blade (FIG. 9E). [0038] FIG. 10 shows test data obtained for an elastomeric check valve in accordance with one embodiment (having the geometry and dimensions shown in FIGS. 1 IB and 11C). FIG. 10 illustrates the measured flow/pressure curve, with a dashed line indicating the flow rate behavior for increasing pressure, and a solid line indicating the behavior for decreasing pressure. The graph shows a cracking pressure at about 4 psi and a closing pressure at about 3 psi. The breakdown pressure falls outside the range of tested backward pressures and, therefore, does not show up in the curve. The tested valve exhibits substantially no backward leakage (i.e., the leak rate is much lower than the design requirement) in the pressure range for which the valve is designed.

[0039] Check valves in accordance with the present invention have commercial

applications for a variety of fluidic and pump devices, including, e.g., drug pumps for external use or implantation. FIG. 11A shows, for example, an ophthalmic micropump 1100 including a drug reservoir 1102 that is connected to an outlet placed, in operation, at the injection site (here, the pars plana of the eye) via a cannula 1104. To avoid undesired backflow of bodily fluids into the drug reservoir 1102, the cannula includes an elastomeric micro check valve that allows fluid flow only from the reservoir towards the outlet. The check valve is shaped and sized to fit within the cannula 1104. For example, in typical ophthalmic micropumps, which have dimensions of 10x8x5 mm, the valve structure has a diameter of about 0.75 mm; dimensions of the valve according to one embodiment are shown in FIGS. 1 IB and 11C. [0040] Although the present invention is described above with reference to specific embodiments and details, the invention is not limited to those embodiments and details. Rather, various additions and modifications to what is expressly described herein, which will be readily apparent to one of skill in the art, are also included within the scope of the invention. Moreover, it is to be understood that the features of the various embodiments described herein can exist in various combinations and permutations without departing from the spirit and scope of the invention. Accordingly, details of the above description are intended for illustration only, and not to be regarded as limiting the scope of the invention, except as and to the extent that they are included in the accompanying claims.

[0041] What is claimed is: