Abstract:
A biocompatible, human implantable apparatus and a method for fully encasing a circuit within a polymer housing. The method may include placing the circuit in a mold, injecting a formulation into the mold, and polymerizing the formulation. The formulation may include monomers and polymers. The apparatus may include a circuit in a polymerized formulation of monomers and polymers.

Description:
This application is a continuation of U.S. patent application Ser. No. 10/825,648, filed Apr. 16, 2004, incorporated herein by reference in its entirety. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the invention 
     The present invention relates to a circuit housing, and, more specifically, to a housing for a circuit designed to be implanted in-vivo (i.e., an implantable circuit). 
     2. Discussion of the Background 
     There are several applications that require a circuit to be protected from the environment in which the circuit is intended to operate. For example, a human implantable glucose sensor circuit must be housed within a suitable housing to both protect the sensor from the human body and to protect the human body from the sensor. U.S. Pat. No. 6,330,464, the disclosure of which is incorporated herein by this reference, discloses such a sensor. 
     A housing encasing an implantable circuit should have at least some of the following characteristics: (1) the ability to protect the electronic circuitry of the sensor from the ambient in-vivo chemical and physical environment, (2) the ability to protect tissue adjacent to the sensor from any adverse reaction which could result as a consequence of contact (or leachables) from within the circuitry—in addition, beyond the adjacent tissue, the encasement must not permit leachables of any detectable significance into the general body environment; (3) the ability to permit wireless electronic communication between the circuitry and an external reader for power and signal; (4) the ability to permit free passage of wavelengths of light necessary for optical functioning of the sensor; (5) the ability to support the surface chemistry required to form a chemical recognition “front-end”; (6) the housing should be high volume manufacture-able; (7) the housing must be non-toxic and “biocompatible”; and (8) provide a sufficiently high reliability to meet the specifications of a medical product. 
     SUMMARY OF THE INVENTION 
     The present invention provides a housing that meets many of the criteria outlined above. In one aspect, the present invention provides a circuit encased within a completely enclosed polymer housing. Preferably, the housing is made of an organic polymer, such as PMMA. In some embodiments, the circuit is first enclosed within a glass housing which itself is then enclosed within a second housing, such as a housing made from an organic polymer. In other embodiments, the circuit is first encased within a brick of epoxy and then the epoxy brick containing the circuit is enclosed within a housing. 
     In another aspect, the present invention provides a method for enclosing a circuit in a polymer housing. In one embodiment, the method may include the following steps: (a) placing the circuit in a mold; (b) pouring a formulation into the mold so that the formulation completely surrounds the circuit, wherein the formulation comprises monomers; and (c) polymerizing the monomers. In step (b), all of the formulation need not be poured at once. For example, in some embodiments, the formulation is poured into the mold until the mold is half full and then after a delay additional formulation is poured into the mold. In some embodiments, the monomers may be MMA monomers. The formulation may further comprise pre-polymerized PMMA. 
     In another embodiment, the method may include the following steps: inserting the circuit into a polymer housing; injecting an optical epoxy into the polymer housing to fill the spaces between the circuit and the inside walls of the housing (in some embodiments the injection is from the bottom up to force out trapped air); capping an open end of the housing; placing the housing containing the optical epoxy and the circuit into a pressure vessel and increasing the pressure and temperature within the vessel; allowing the optical epoxy to cure; and removing the housing from the pressure vessel. 
     In another embodiment, the method may include the following steps: inserting the circuit into a glass housing; injecting an optical epoxy into the glass housing to fill the spaces between the circuit and the inside walls of the housing; injecting an optical epoxy into a polymer housing; inserting into the polymer housing the glass housing containing the circuit; capping an open end of the glass housing; and capping an open end of the polymer housing. 
     The above and other features and advantages of the present invention, as well as the structure and operation of preferred embodiments of the present invention, are described in detail below with reference to the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings, which are incorporated herein and form part of the specification, help illustrate various embodiments of the present invention and, together with the description, further serve to explain the principles of the invention and to enable a person skilled in the pertinent art to make and use the invention. In the drawings, like reference numbers indicate identical or functionally similar elements. Additionally, the left-most digit(s) of a reference number identifies the drawing in which the reference number first appears. 
         FIG. 1  illustrates one embodiment of a circuit assembly according to the present invention. 
         FIG. 2  is a flow chart illustrating a process, according to one embodiment, for encasing a circuit within a polymer housing. 
         FIG. 3  is a cross sectional view of a circuit assembly according to an embodiment of the invention. 
         FIG. 4  is a flow chart illustrating a process, according to another embodiment, for encasing a circuit within a polymer housing. 
         FIG. 5  is an exploded view of a circuit assembly according to an embodiment of the invention. 
         FIG. 6  is a cross sectional view of a circuit assembly according to another embodiment of the invention. 
         FIG. 7  illustrates a circuit assembly according to another embodiment of the present invention. 
         FIG. 8  is an exploded view of a circuit assembly according to another embodiment of the invention. 
         FIG. 9  is a flow chart illustrating a process, according to another embodiment, for encasing a circuit within a polymer housing. 
         FIGS. 10A and 10B  illustrate a circuit covered with different amount of epoxy. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       FIG. 1  illustrates one embodiment of a circuit assembly  100  according to the present invention. As shown in  FIG. 1 , the present invention provides an assemblage including a circuit  101  housed within a fully enclosed housing  102 . Preferably, as shown in  FIG. 1 , housing  102  is capsule shaped, but other shapes may be used. Circuit  101  may be an electronic circuit having a printed circuit board  110  and one or more electrical and optical components  112  attached to the circuit board  110 . Circuit  101  may include a conventional sensor, such as the sensor described in U.S. Pat. No. 6,304,766. The housing  102  may be a housing made from PMMA, which is a polymer of methyl methacrylate (MMA) monomers, or from other organic polymers. 
       FIG. 2  is a flow chart illustrating a process  200 , according to one embodiment, for creating circuit assembly  100 . Process  200  may begin in step  202 , where a polymerization initiator is added to a mold. In step  204 , an encasement formulation containing monomers is poured into the mold (e.g., filling the mold halfway). In step  206 , circuit  101  is placed in the mold. In step  208 , more of the encasement formulation is poured into the mold so that the circuit is completely immersed in the encasement formulation. In one embodiment, the encasement formulation includes monomers. In one embodiment, the encasement formulation consists of or essentially consists of MMA monomers. In this manner, one can encase circuit  101  in a polymer housing. 
     In some situations, for example, situations where the formulation includes MMA monomers and circuit  101  is relatively large, circuit  101  can become severely damaged during the polymerization process (i.e., during step  206 ). The cause of this damage is usually attributed to the shrinkage that occurs naturally during polymerization of MMA. In the joining of bonds between monomers contained within a neat solution of MMA, the intermolecular spacing is reduced within a polymer as the reaction progresses. This is a well-known phenomena and typical of most, if not all, polymer reactions. The net volumetric shrinkage that occurs during the polymerization of PMMA from neat monomer solution is approximately 14%. 
     This shrinkage can, in some circumstances, create a particular problem when using PMMA as a circuit housing because, as the encasement reaction progresses, and the viscosity increases as the shrinkage occurs simultaneously, the electrical components  112 , which are mounted on the circuit board  110  typically with conductive epoxy, are pulled from the circuit board  110  during the polymerization process. 
     The relative strength of the conductive epoxy used to hold the components  112  in place, which conductive epoxy is formulated primarily and maximally for its electrical conductance and cure properties, does not have sufficient mechanical strength to withstand the pull and stress from PMMA shrinkage as the encasement reaction progresses. Consequently, some attempts to encase a circuit from an MMA monomer encasement formulation result in a non-functional circuit because of un-repairable mechanical damage. 
     To solve this problem, one aspect of the present invention is a method by which the polymerization reaction can be conducted without damage to the encased circuit  101 . Because pre-polymerized PMMA of large molecular weights (approximately up through 1 million+mw) can be dissolved in MMA monomer, and because the shrinkage is a direct result of bonds forming from discrete monomers, one possible solution is to formulate the encasement formulation to include a portion of MMA monomer and a portion of pre-polymerized PMMA dissolved within the MMA monomer. 
     The net shrinkage is proportional to the amount of monomer which is reacted to become polymer within the overall volume. If the overall encasement formulation volume, is portioned to include, for example, about 70% pre-polymerized PMMA, and about 30% un-reacted MMA monomer (into which the 70% PMMA has been dissolved), then the degree of shrinkage which occurs drops in direct proportion to the monomer component within the overall volume. In practice, an encasement formulation of 100% MMA monomer shrinks volumetrically about 14% overall. By dropping the formulation to only 30% MMA, shrinkage in the amount of approximately 0.3×14=4.3% would be expected. In practice, approximately 4% shrinkage is measured from making this improvement. 
     Accordingly, the result of altering percent solids provides an improvement in system stress during encasement by reducing shrinkage from, for example, 14% to 4% by reformulating MMA/PMMA specifically for the encasement process. Formulation ratios of 60-80% PMMA in MMA are preferred, although not required, because of a present practical limitation. Although to a point, higher ratio values would be expected to reduce shrinkage proportionately, and further reduction in shrinkage may be possible. As a practical matter, the solution viscosity becomes extremely high at these higher ratio levels making the high solids solution extremely difficult to handle, transfer, etc. 
     In some situations, however, even with 4% shrinkage, which is a great improvement over 14%, some percentage (about 40-50%) of circuits  101  can not withstand the 4% shrinkage of the encasement. The surviving circuits tend to have greater amounts of conductive epoxy to increase mechanical strength slightly of the surface mounted parts. However, conductive epoxy is not sufficiently strong, and to increase the amount used per connection beyond good manufacturing standards would then create other problems. Another important consideration is for wire-bonded circuits. These “frog hair” gold wires are typically 25 microns in diameter which is about ⅓ to ¼ the diameter of a typical human hair. Small amounts of movement relative to the fixed board components can rip these wires from the attachments. 
     Accordingly, in some applications, it is desirable to mechanically strengthen the circuit  110  to allow it to withstand the remaining shrinkage from the PMMA encasement cure reaction. 
     One way to mechanically strengthen circuit  101  to allow it to withstand the remaining 4% shrinkage from the PMMA (70/30) encasement cure reaction, is to reinforce the circuit with a pre-applied epoxy layer. For example, following assembly of the electrical components to the circuit board and cleaning of the assembly, an epoxy is applied over the circuit, which epoxy both under-fills and overfills the components attached to the circuit board. Surprisingly, it was discovered that this solution works best when the applied epoxy covers the components in such a way as to result in a relatively “smooth” surface topology, but this is not a requirement. This “smooth” surface topology is illustrated in  FIG. 10A . For comparison,  FIG. 10B  shows a “non-smooth” epoxy coating. As shown in  FIG. 10A , the surface  1002  of the epoxy coating is smooth or substantially smooth. 
     Although the epoxy adequately strengthens circuit  101  against damage from the shrinking polymer, the resultant stress caused by the remaining 4% shrinkage then becomes manifest as de-lamination between the adjoining surfaces of epoxy and PMMA within the final encasement. As mentioned above, it was discovered that if the surface was smoothed by the volume and application of the epoxy pre-coat, not allowing the PMMA to get a “grip” within the surface topology, then de-lamination was less likely to occur. The stress from the 4% remaining shrinkage is then absorbed as internal stress within the PMMA encasement body itself. This stress may be removed in a conventional way by annealing in a final operation. 
     Some or all of the epoxy used to reinforce the circuit  110  may, in some embodiments, include a light blocking pigment (such as black or wavelength specific) which prevents unwanted light propagation and scatter about the circuit, thereby increasing the optical signal to noise ratio of the system. 
     In some embodiments, to prolong the life of the circuitry  101 , it may be desirable to prevent molecular water vapor that has seeped through the housing  102  from condensing to become liquid water. If liquid water cannot form from the water vapor, then potential ion contaminants present cannot become solvated, which can lead to circuit failure. 
     One way to prevent the water vapor from condensing is to prevent the formation of heat induced bubbles in the encasement polymer. MMA monomer is extremely volatile. The polymerization reaction of MMA to PMMA is also exothermic. The exothermic heat yield from a typical reaction begun at room temperature will commonly increase the temperature as the reaction progresses to a point where the remaining un-reacted monomer will boil and create bubbles of all sizes trapped within the cured polymer. To prevent any possibility of heat induced micro-bubbles and voids within the housing where water vapor could condense, substantial overpressure may be used during the polymerization reaction. More specifically, in a preferred embodiment, a mold containing PMMA/MMA is placed within a pressure reactor that is then pressurized to a pressure that exceeds the vapor pressure of MMA monomer at the polymerization temperature. This pressurization process both prevents bubbles and provides a very close mechanical surface bond with the underlying epoxy coat which does not delaminate once formed. The housing is clear and without bubble or void defects to prevent water from condensing, and as an important byproduct, provides excellent optical clarity without bubble defect. 
     Referring now to  FIG. 3 ,  FIG. 3  is a cross sectional view of circuit assembly  100 , according to one embodiment, along line A. As shown in  FIG. 3 , the circuit  101  may be fully encased within a brick of epoxy  302  (or “epoxy brick  302 ”), which is encased within housing  102 . 
       FIG. 4  is a flow chart illustrating a process  400 , according to another embodiment, for creating circuit assembly  100 . Process  400  may begin in step  402 , where a housing  500  (e.g., a sleeve  500  or tube or other housing having an open end) (see  FIG. 5 ) is created along with a plug  504  for plugging the opening in the housing. For example, a cylindrical sleeve  500  and plug  504  may be machined from a polymer rod, such as a rod of PMMA or other organic polymer. As shown in  FIG. 5 , sleeve  500  may have a notch  592  adjacent to the open end  594  of sleeve  500 . If sleeve  500  and plug  504  are made from PMMA, the PMMA sleeve and plug may be annealed at approximately 80° C. for about four hours (step  403 ). 
     In step  404 , epoxy is applied over the circuit  101  so that the circuit is partially or fully encased within an epoxy brick  502 , thereby forming an assembly  503 . In step  406 , assembly  503 , sleeve  500  and plug  504  are cleaned. For example, assembly  503 , sleeve  500  and plug  504  may be cleaned by rubbing a Q-tip with IPA on the surfaces thereof. In step  408 , an optical epoxy is prepared. EPO-TEK 301-2 Epoxy from Epoxy Technology of Billerica, Mass. and other epoxies may be used as the optical epoxy. 
     In step  410 , the circuit encased within the epoxy brick (i.e., assembly  503 ) is placed into the sleeve  500 . In step  412 , the prepared optical epoxy is injected (i.e., introduced) into sleeve  500 . Preferably, no bubbles in the optical epoxy are formed during step  412 . In step  414 , the plug  504  is placed into the open end of sleeve  500 , thereby sealing the open end of the sleeve. 
       FIG. 6  is a cross sectional view, according to one embodiment, of the circuit assembly  100  along line A after step  414  is performed. In the embodiment shown in  FIG. 6 , the circuit  101  is fully encased within an epoxy brick  502 . The epoxy brick  502 , which houses circuit  101  is placed within sleeve  500 , which may be a cylindrical sleeve. When sleeve  500  is a cylindrical sleeve and when circuit  101  is fully encased within the epoxy brick, it is preferable that the distance between the upper right hand corner and lower left corner of epoxy brick  502  be equal to or slightly less than the inner diameter of sleeve  502 . That is, in some embodiments it is preferable that w=sqrt ((d*d)−(h*h)), where w is the width of assembly  503 , h is the height of assembly  503 , and d is the inner diameter of sleeve  500 . In embodiments where the assembly  503  does not have a uniform width or has a circular shaped cross section, then the maximum width of the assembly may be equal to or slightly less than the inner diameter. As illustrated in  FIG. 6 , the optical epoxy (e.g., a refractive index (RI) matching epoxy) fills spaces between assembly  503  and sleeve  500 . 
     Referring back to  FIG. 4 , in step  416 , the new assembly (i.e., the sealed sleeve containing the epoxy and assembly  503 ) is placed into a pressure vessel. In step  418 , the pressure within the vessel is increased to about 125 psi using Nitrogen or other inert gas. In step  420 , the optical epoxy is cured for an amount of time (e.g., 20 hours) at a predetermined temperature (e.g., 40° C.). After the predetermined amount of time has elapsed, the assembly is removed from the pressure vessel and then final machined (step  422 ). 
     The method described above allows the possibility of annealing a PMMA housing before encasement without putting any additional stress on the circuit  101 . 
       FIG. 7  illustrates an alternative circuit assembly  700  of the present invention. Circuit assembly  700  is similar to circuit assembly  100  in that assembly  700  includes a circuit  101  housed within a housing  102 . However, in assembly  700 , the circuit  101  is also housed within a glass housing  702  (e.g., a tube or other shaped housing), which itself is housed within the housing  102 . The glass housing  702 , in some embodiments, is closed at one end and open at the opposite end. The open end may be plugged by a glass ball  704  or other suitable plug.  FIG. 8  is an exploded view showing the components of assembly  700 , according to one embodiment. Glass housing  702 , in some embodiments, may be constructed from an infra-red (IR) blocking glass. 
       FIG. 9  is a flow chart illustrating a process  900 , according to one embodiment, for making assembly  700 . Process  900  may begin in step  902 , where a sleeve and a plug, such as sleeve  500  and plug  504 , are created. 
     In step  904 , the sleeve and plug are annealed. The sleeve and plug may be annealed at 80° C. for about four hours. In step  906 , the components (e.g., sleeve  500 , plug  504 , glass housing  702 , glass ball  704 , epoxy brick  502 , etc.) are cleaned. For example, sleeve  500  and plug  504  may be cleaned in an ultrasonic bath with IPA followed by a rinse step, and glass housing  702  and glass ball  704  may also be cleaned ultrasonically with KOH/alcohol solutions and then rinsed with water. 
     In step  908 , a bonding agent is applied to the glass housing  702  and glass ball  704 . The bonding agent used may be trimethoxy [2-(7-oxabicyclo [4.1.0]hept-3-yl)ethyl] silane, which may be purchased from Sigma-Aldrich Corporation (catalog no. 413321) 
     In step  910 , a batch of optical epoxy is prepared. In step  912 , the epoxy coated circuit board is inserted into the glass housing. In step  914 , some of the prepared epoxy is injected into the glass housing  702 . 
     In step  916 , some of the prepared epoxy is injected into the sleeve  500 . In step  918 , glass housing  702 , which houses the circuit, is inserted into an open end of the sleeve. In step  920 , the glass ball  704  is inserted into the open end of glass housing  702 , thereby sealing the open end of the glass housing. In step  922 , the plug  504  is used to seal the open end of the sleeve. 
     In step  924 , the sealed sleeve, which houses glass housing  702 , which houses the circuit  101 , is placed into a pressure vessel where the pressure is increased to about 125 psi using an inert gas and the temperature is increased to about 40° C. After about  20  hours, the pressure is gradually reduced and the assembly is removed from the pressure vessel and then final machined (step  926 ). 
     Although the above described processes are illustrated as a sequence of steps, it should be understood by one skilled in the art that at least some of the steps need not be performed in the order shown, and, furthermore, some steps may be omitted and additional steps added. 
     While various embodiments/variations of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.