US20060227513A1

US20060227513A1 - Controlling biological fluids in microelectromechanical machines

Info

Publication number: US20060227513A1
Application number: US11/153,788
Authority: US
Inventors: Terry Dishongh; Jason Cassezza; Kevin Rhodes; Bradford Needham
Original assignee: Intel Corp
Current assignee: Intel Corp
Priority date: 2005-04-11
Filing date: 2005-06-15
Publication date: 2006-10-12
Also published as: US7652372B2; TWI298937B; JP4966962B2; EP1869703A1; US20060227512A1; TW200636955A; WO2006110903A1; JP2008536337A

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

This application is a continuation-in-part of U.S. application Ser. No. 11/103,216, filed Apr. 11, 2005.

BACKGROUND

This invention relates generally to microelectromechanical systems used in biological applications.
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

FIG. 1 is a greatly enlarged, cross-sectional view in accordance with one embodiment of the present invention;
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;
FIG. 3 is a cross-sectional view corresponding to FIG. 1 in use in accordance with one embodiment of the present invention;
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;
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;
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;
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
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

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Claims

1. A method comprising:

providing a microelectromechanical system valve to sense the need to dispense a therapeutic agent.

2. The method of claim 1 including forming a microelectromechanical system valve in the form of a leaf valve.

3. The method of claim 2 including forming a depression in a first substrate and forming said valve over said depression.

4. The method of claim 3 including forming a trench through a second substrate and securing said first substrate and said second substrate together.

5. The method of claim 1 including providing fluidic trips to form turbulent flow proximate to said valve to mix fluid controlled by said valve.

6. The method of claim 5 including forming said valve with a bioactive material.

7. The method of claim 6 including forming a bimetal valve.

8. The method of claim 6 including forming a polymer layer on said valve, said polymer layer including inert particles.

9. The method of claim 8 including functionalizing said inert particles.

10. The method of claim 9 including arranging said valve to be actuated in response to a chemical reaction with material on said inert particles.

11. A dispensing device comprising:

a first flow passage;

a second flow passage; and

a microelectromechanical system valve to control the flow of fluid from one passage to the other, said system including fluidic trips to cause turbulent flow and mixing the fluids from said first and second flow passages.

12. The device of claim 11 wherein said valve is a leaf valve.

13. The device of claim 12 including a pair of substrates, said first flow passage formed in one substrate and said second flow passage formed in the other substrate and said valve formed between said substrates.

14. The device of claim 11 wherein said valve includes a bioactive material.

15. The device of claim 11 wherein said valve is a bimetal valve.

16. The device of claim 15 wherein said valve includes a bioactive material.

17. The device of claim 14 including a polymer layer and said bioactive material is embedded in said polymer layer.

18. The device of claim 17 including inert particles embedded in said polymer layer, said inert particles including a reactive material coated on said particles.

19. The device of claim 14 wherein said valve is operable in response to the extent of reactions with said bioactive material.

20. An apparatus comprising:

a pair of passages;

a valve to selectively control the extent of communication between said passages, said valve including a bioactive material, said valve operable in response to chemical reactions with said bioactive material.

21. The apparatus of claim 20 wherein said valve is a leaf valve.

22. The apparatus of claim 20 wherein said valve is a microelectromechanical system valve.

23. The apparatus of claim 20 wherein said valve includes a layer having a coating of bioactive material.

24. The apparatus of claim 23 wherein said layer includes inert particles having a bioactive coating thereon.

25. The apparatus of claim 24 wherein said inert particles are in the form of glass beads.

26. The apparatus of claim 25 including a polymer layer and wherein said glass beads are embedded in said polymer layer.

27. The apparatus of claim 20 wherein reactions with said bioactive material open said valve when sufficient accumulation occurs on said valve to pull said valve open.