Methods for hermetically sealing microchip reservoir devices

Metal fusion bonding – Process – Using high frequency vibratory energy

Reexamination Certificate

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C228S124600, C219S121640

Reexamination Certificate

active

06827250

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention is generally in the field of implantable miniaturized devices that provide controlled delivery or exposure of molecules or smaller devices. More specifically, the invention relates to implantable microchip devices.
U.S. Pat. No. 5,797,898 to Santini, et al. describes active or passive microchips for the delivery, i.e. release, of molecules such as drugs. These microchip devices contain reservoirs filled with the molecules to be released. In some embodiments, the reservoir openings must be sealed after they are filled to prevent leakage from or between any of the reservoirs.
One approach for sealing small reservoirs is to use a waterproof epoxy or other material impervious to any fluids surrounding the device. It is generally important, however, to avoid contacting the reservoir contents, particularly drug molecules, with chemical adhesives. The use of a chemical adhesive sealant may necessitate additional testing to determine the presence and nature of any interactions between the chemical adhesive and each drug or other chemical to be contained in and released from the reservoirs. The use of chemical adhesives also may require long times, high temperatures, and/or exposure to ultraviolet light in order to cure completely, processes that may degrade sensitive drug or chemical molecules in the reservoirs.
It is known that such adhesives and polymers generally cannot function as true hermetic seals over extended periods of time. Hermeticity, however, would be highly advantageous for microchip reservoirs to provide a controlled environment until the reservoirs are activated (i.e. opened). In fact, hermeticity likely is essential for most long term in vivo applications of such microchip devices. It would therefore be beneficial to provide methods of hermetically sealing a microchip device, including any control electronics and power source packaged with the device.
While hermetic sealing techniques are commonly found in implantable devices, such as pacemakers and cochlear implants, new or improved hermetic sealing methods are required for hermetically bonding a microchip reservoir device to an outer enclosure/packaging structure, which serves to protect the internal device components while also allowing a portion of the microchip reservoir device to contact/interface with the environment.
It would be desirable for seals incorporated within a microchip device for in vivo applications to prevent communication of drug, body fluids, or other substances between reservoirs or from the reservoirs into other portions of the microchip device. In addition, the seal desirably should withstand mechanical forces and chemical attack over time, and should not interfere with the process of opening reservoir caps and other aspects of the release processes. The materials forming the seals desirably are biocompatible, biostable, have very low or no permeability to water vapor and other materials, and should not react with the drug or other reservoir contents. Furthermore, the process of sealing should not degrade the reservoir contents, for example due to high temperatures, excessive vibratory forces, or exposure to incompatible chemicals or materials. It therefore would be advantageous to provide devices and methods for sealing the reservoirs of microchip devices for the controlled release of drugs and other molecules, which satisfy these several sealing parameters.
SUMMARY OF THE INVENTION
Methods are provided for hermetically sealing the reservoirs of microchip devices and for hermetically sealing the substrate assemblies in a hermetic packaging structure. In one embodiment, the method comprises (1) providing a primary substrate having a front side and a back side, the substrate comprising a plurality of reservoirs positioned between the front side and the back side, each reservoir being loaded with molecules or a secondary device for controlled release or exposure, the reservoirs having at least one opening in need of sealing, the primary substrate including one or more hermetic sealing materials; (2) providing a hermetic sealing substrate having a surface composed of one or more hermetic sealing materials; (3) positioning the hermetic sealing substrate over the reservoir openings and contacting said hermetic sealing materials of the primary substrate with said hermetic sealing materials of the hermetic sealing substrate; and (4) applying energy or a mechanical force to the contacted sealing materials effective to form a hermetic seal between the hermetic sealing substrate and the primary substrate to hermetically seal the reservoir openings.
In one embodiment, the energy can be applied through a welding process, such as one that comprises ultrasonic welding or laser welding. In another embodiment, the energy can be applied by heating to cause a reaction between the hermetic sealing materials of the primary substrate and the hermetic sealing materials of the hermetic sealing substrate. Preferably, the reaction is a eutectic reaction, for example, to form a eutectic bond comprising a eutectic composition selected from gold/silicon, gold/germanium, gold/tin, gold/indium, lead/tin, lead/indium, and platinum/silicon. The heating could comprise, for example, localized resistive heating using a patterned resistor, or could be provided by a laser.
In still other embodiments, the hermetic sealing material of the hermetic sealing substrate can comprise a metal gasket and a compressive force could be applied in an amount effective to deform the metal gasket around each reservoir opening. Tapered structures extending from the primary substrate surface could be used to concentrate the compressive forces at areas around the reservoir opening.
The hermetic sealing substrate preferably comprises or consists of a metal film or metal foil. In other embodiments, the hermetic sealing materials of the primary substrate, of the sealing substrate, or both, can comprise, for example, a silicate glass and/or a metal selected from gold, platinum, titanium, palladium, tantalum, aluminum, and stainless steel. Preferably, the primary substrate comprises a hermetic material selected from the group consisting of ceramics, metals, silicon, or glasses.
In some embodiments, the hermetic sealing substrate is a reservoir cap which can selectively be disintegrated to release or expose the molecules or secondary device. In a preferred embodiment, the molecules are drug molecules. In one method to form reservoir caps, the front side of the substrate comprises metal traces and the hermetic sealing substrate is welded onto the metal traces. In other embodiments of the sealing method, the reservoir end distal the opening in need of sealing comprises the reservoir caps.
In one embodiment, the method includes the optional step of applying a protective coating material, such as a polymer, over the hermetic sealing substrate, on a surface distal the surface that contacts the hermetic sealing materials of the primary substrate, before or after the reservoirs are hermetically sealed.
In another embodiment, the hermetic sealing substrate is a multi-layered structure comprising a glass layer which is anodically bonded to the primary substrate, wherein the glass layer has apertures in communication with the reservoirs. The multi-layered structure can further include a patterned metal layer which is anodically or eutectically bonded to the glass layer on the side distal the primary substrate, wherein the patterned metal layer has apertures in communication with the reservoirs and with the apertures in the glass layer. The multi-layered structure can further comprise a metal foil which is laser welded to the patterned metal layer on the side distal the glass layer, to hermetically seal the space defined by the reservoirs and apertures.
In one aspect, a method is provided for packaging an active-release microchip device which comprises: (1) providing a microchip device having a substrate, a plurality of reservoirs containing contents for release or exposure, and reservoir caps over the reservoir contents

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