Abstract:
A therapeutic agent may be dispensed into a biological fluid on an as needed basis. A microelectromechanical system valve may dispense the therapeutic agent as needed. The valve may sense the extent of the need for the therapeutic agent and may controllably open to provide that therapeutic agent in response thereto.

Description:
RELATED APPLICATION  
       [0001]     This application is a continuation-in-part of U.S. application Ser. No. 11/103,216, filed Apr. 11, 2005. 
     
    
     BACKGROUND  
       [0002]     This invention relates generally to microelectromechanical systems used in biological applications.  
         [0003]     Semiconductor fabricated machines of extremely small dimensions have potential medical applications. For example, microelectronic machines may be provided within external apparatus for the control of patient treatment. In addition, microelectronic mechanical systems may be sufficiently small that they may be implanted in situ to provide patient treatment. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0004]      FIG. 1  is a greatly enlarged, cross-sectional view in accordance with one embodiment of the present invention;  
         [0005]      FIG. 2  is a greatly enlarged, cross-sectional view taken generally along the line  2 - 2  in  FIG. 1  in accordance with one embodiment of the present invention;  
         [0006]      FIG. 3  is a cross-sectional view corresponding to  FIG. 1  in use in accordance with one embodiment of the present invention;  
         [0007]      FIG. 4  is a cross-sectional view taken generally along the line  4 - 4  in  FIG. 1  in accordance with one embodiment of the present invention;  
         [0008]      FIG. 5  is a cross-sectional view taken generally along the line  5 - 5  in  FIG. 1  in accordance with one embodiment of the present invention;  
         [0009]      FIG. 6  is an enlarged, cross-sectional view corresponding to  FIG. 1  at an early stage of manufacture in accordance with one embodiment of the present invention;  
         [0010]      FIG. 7  is an enlarged, cross-sectional view corresponding to  FIG. 6  at a subsequent stage of manufacture in accordance with one embodiment of the present invention; and  
         [0011]      FIG. 8  is an enlarged, cross-sectional view corresponding to  FIG. 7  at a subsequent stage of manufacture in accordance with one embodiment of the present invention. 
     
    
     DETAILED DESCRIPTION  
       [0012]     Referring to  FIG. 1 , an apparatus  10  may be implanted within a patient or may be external to the patient. Fluid, indicated as A, may flow in and through the device  10 . For example, the flow of fluid A may be a flow of blood which is to be treated with appropriate therapeutic agents. The therapeutic agents, indicated as B, may flow from the passage  14   a  under control of a microelectromechanical system (MEMS) leaf valve  16 . In other words, the valve  16  controls the flow of fluid B from the channel  14   a  into the channel  14   b  and thereby regulates the therapeutic treatment.  
         [0013]     In one embodiment, the apparatus  10  may be made in two parts, including an upper part  12   b  and a lower part  12   a . The two parts  12  may be permanently joined along the junction surface  12   c  in one embodiment of the present invention. Thus, the part  12   b  may have a passage  14   a  formed therein to allow the passage of the fluid B while the part  12   a  may have the passage  14   b  formed in it. The parts  12   a  and  12   b  may be fabricated using semiconductor fabrication techniques in some embodiments of the present invention. The passages  14   b  and  14   a  may be formed by conventional lithographic techniques in one embodiment.  
         [0014]     Controlling the communication between the passages  14   a  and  14   b , a leaf valve  16  includes a first portion  16   a  secured to the part  12   b  and a second portion  16   b  cantilevered over the passage  14   a  in the part  12   a . Also formed on the surface  12   c  and, particularly, in one embodiment, the outside surface of the part  12   b , are a plurality of roughenings or fluidic trips  18 . At least some of the trips  18  may be located on the surface  12   c  proximate to the passage  14   a.    
         [0015]     The trips  18  function to create turbulent flow at the interface between the passages  14   a  and  14   b . The turbulent fluidic flow assists in mixing the two fluids A and B. Thus, the flow of biological fluid to be treated, indicated at A, may be treated with the liquid, indicated at B, through a mixing action facilitated by the trips  18 , especially when the valve  16  is opened.  
         [0016]     The valve  16  may be formed of a flexible, multilayer structure. The lowest layer may include aluminum covered by copper  22 . The layers  24  and  22  have different coefficients of thermal expansion in some embodiments and, therefore, may bend in controllable ways in response to heating. For example, the makeup of layers  22  and  24  may be similar to that used in switches for thermostat control.  
         [0017]     Over the layer  22  may be situated a polymer layer  20  having formed therein with a coated inert particles such as glass beads  26 . Some of the glass beads  26  extend out of the surface of the layer  20 , as indicated at  26   a , and others are intermeshed within the polymer as indicated at  26   b . The glass beads  26  may function as carriers for biological agents. Structures other than glass beads may also be used.  
         [0018]     The glass beads  26  may be coated with an appropriate functionalizing material which, in one embodiment, includes reactive components, such as free radicals, to react with passing molecules. For example, the glass beads  26  functionalized with a protein streptavidin may be coated with a layer including deoxyribonucleic acid (DNA). In other words, the glass beads  26   a  may be coated with an appropriate material having free reactive radicals to react with passing molecules. In one embodiment, this means that materials in the blood, passing through the passage  14   b , may react and adhere to the exposed glass beads  26   a . The glass beads  26  may be considered bioactive glass beads which are receptive to bio-agents, such as proteins, which attach to the free radicals on the glass beads  26   a  i n one embodiment. “Bioactive” encompasses any material that may have an effect on any living tissue.  
         [0019]     As one application, an in vitro delivery of medication may be made to blood passing through the apparatus  10 , passage  14   a . A species within the passing blood may react with the bioactive glass beads  26   a  that are exposed on the valve  16 . The reactive constituents adhere to the glass beads  26   a  and more, particularly, to a reactive coating on the beads  26   c.    
         [0020]     Thus, in one embodiment, shown in  FIG. 3 , the reactive constituents in the blood collect on the surface of the valve  16  as indicated at C. The weight of these constituents pulls the valve  16  open by hingedly rotating the valve portion  16   b  in a cantilevered fashion downwardly and away from the passage  14   a , still secured at portion  16   a , to the part  12   b . As shown in  FIG. 3 , as a result of the action of the fluidic trips  18 , turbulent flow is generated, as indicated by the arrows D, facilitating the mixing of the fluid B in the passage  14   a  with the fluid A in the passage  14   b.    
         [0021]     Referring to  FIG. 4 , the passage  14   a , in one embodiment, may be a circular portion  14   e  that includes a connecting portion  14   d  which connects to a source of therapeutic agent. Proximate to the downstream edge of the passage  14   a  may be the fluidic trips  18 . In some embodiments, the fluidic trips  18  may cover the entire exposed surface  12   c  of the portion  12   b.    
         [0022]     Referring to  FIG. 5 , the part  12   a  may include the passage  14   b  formed therein. The passage  14   b  may be a trench aligned with the circular portion  14   e  of the passage  14   a.    
         [0023]     Referring to  FIGS. 6-8 , in accordance with one embodiment of the present invention, the apparatus  10  may be fabricated in an inverted fashion beginning in  FIG. 6 . There, a substrate, forming the part  12   b , may have a passage  14   a  formed therein. The passage  14   a  may be filled with a material  30  which may be relatively easily removed, for example, by exposure to heat.  
         [0024]     Over the material  30  and the part  12   b  may be deposited a layer that will form the valve  16 . The layer that will form the valve  16  is then patterned and etched to form the portion  16   a  adhered to the part  12   b  and the portion  16   b  which, at this point, is still adhered to the material  30  that fills the passage  14   a.    
         [0025]     In one embodiment, the trips  18  may be formed as incompletely removed portions of the layer that forms the valve  16 . In such case, the trips  18 , which may be surface roughenings, may extend across the upper exposed surface  12   c  of the part  12   b  at the stage shown in  FIG. 7 . In other embodiments, after etching and defining the valve  16 , a coating (not shown) may be applied thereover which is sufficiently rough to form the trips  18 . In still another embodiment, that coating may be partially removed by etching, leaving residue which acts as the trips  18 .  
         [0026]     Then, as shown in  FIG. 8 , the material  30  may be removed by conventional techniques including the application of heat and the removal by decomposition of the material  30 . An example of such a material is a polymer such as polycarbonate and polynorbornene. This forms the open passage  14   a , better shown in  FIG. 4 . This removal also frees the free cantilevered end portion  16   b  of the valve  16  to be movable into the passage  14   b . Then, the two parts  12   b  and  12   a  may be secured together using adhesive or other techniques. As a result, the passage  14   b  can receive fluids, indicated as A, and mix into those fluids, the fluid B in the passage  14   a.    
         [0027]     In some embodiments, the reaction between the treatment agent and the biological fluid may be controlled on an as needed basis. In other words, instead of simply flooding the body with extra treatment agents, such as drugs, that amount of therapeutic agent may be provided which is actually needed. As a result, the body is free from being exposed to excessive concentrations of the treatment agents in some embodiments. In addition, under-treatment may be reduced as well in some embodiments. Thus, in some embodiments, just the right amount of therapeutic agents may be provided.  
         [0028]     While the present invention has been described with respect to a limited number of embodiments, those skilled in the art will appreciate numerous modifications and variations therefrom. It is intended that the appended claims cover all such modifications and variations as fall within the true spirit and scope of this present invention.