U.S. patent application number 10/208309 was filed with the patent office on 2004-02-05 for low temperature anodic bonding method using focused energy for assembly of micromachined systems.
Invention is credited to Cho, Steven T..
Application Number | 20040020173 10/208309 |
Document ID | / |
Family ID | 31186792 |
Filed Date | 2004-02-05 |
United States Patent
Application |
20040020173 |
Kind Code |
A1 |
Cho, Steven T. |
February 5, 2004 |
Low temperature anodic bonding method using focused energy for
assembly of micromachined systems
Abstract
A method for assembling a medicine delivery system (10) includes
providing a substrate (16) with a plurality of compartments (18),
filling the compartments (18) with medicine (34), covering the
compartments (18) with a cap (24), heating the system (10) at a
relatively low temperature, applying a voltage bias (56) across the
substrate (16) and the cap (24), and applying focused energy (54)
to the substrate (16) and/or the cap (24) to seal them together and
create a vacuum in the compartments (18).
Inventors: |
Cho, Steven T.;
(Castroville, CA) |
Correspondence
Address: |
STEVEN F. WEINSTOCK
ABBOTT LABORATORIES
100 ABBOTT PARK ROAD
DEPT. 377/AP6A
ABBOTT PARK
IL
60064-6008
US
|
Family ID: |
31186792 |
Appl. No.: |
10/208309 |
Filed: |
July 30, 2002 |
Current U.S.
Class: |
53/487 ; 156/146;
156/272.2; 53/471; 53/478 |
Current CPC
Class: |
A61M 2205/0244 20130101;
A61K 9/0097 20130101; A61K 9/0009 20130101 |
Class at
Publication: |
53/487 ; 53/471;
53/478; 156/146; 156/272.2 |
International
Class: |
B65B 007/28 |
Claims
What is claimed is:
1. A method for bonding substrates in a micromachined system, the
method comprising the steps of: providing a first substrate and a
second substrate; placing the first substrate in contact with the
second substrate; applying heat to the micromachined system;
applying a voltage bias across the first substrate and the second
substrate; and applying focused energy to at least one of the first
substrate and the second substrate to seal the first substrate to
the second substrate.
2. The method according to claim 1, wherein the first substrate is
made of glass and the second substrate is made of silicon.
3. The method according to claim 1, wherein the heat is less than
100 degrees C.
4. The method according to claim 1, wherein the voltage bias is
between 100 V and 1 kV.
5. The method according to claim 1, wherein the focused energy is
provided by an energy source selected from a group of energy
sources consisting of a microwave, a laser, an infrared, and a lamp
source.
6. The method according to claim 1, wherein the focused energy has
a wavelength less than 600 nm.
7. The method according to claim 1, wherein the micromachined
system is a medicine delivery system, wherein the first substrate
includes a plurality of compartments each having charging openings
for receiving medicine, and wherein the second substrate forms a
cap that covers the charging openings.
8. A method for assembling a medicine delivery system, the method
comprising the steps of: providing a substrate, having a plurality
of compartments, and a cap; charging each of the plurality of
compartments with medicine; covering the plurality of compartments
with the cap; applying heat to the medicine delivery system;
applying a voltage bias across the substrate and the cap; and
applying focused energy to at least one of the substrate and the
cap to seal the cap to the substrate and to create vacuum in the
plurality of compartments.
9. The method according to claim 8, wherein the substrate is made
of glass and the cap is made of silicon.
10. The method according to claim 8, wherein the heat is less than
100 degrees C.
11. The method according to claim 8, wherein the voltage bias is
between 100 V and 1 kV.
12. The method according to claim 8, wherein the focused energy is
provided by an energy source selected from a group of energy
sources consisting of a microwave, a laser, an infrared, and a lamp
source.
13. The method according to claim 8, wherein the focused energy has
a wavelength less than 600 nm.
14. A method for assembling a medicine delivery system, the method
comprising the steps of: providing a substrate, having a plurality
of compartments, and a cap, wherein the substrate is made of glass
and the cap is made of silicon; charging each of the plurality of
compartments with medicine; covering the plurality of compartments
with the cap; applying heat to the medicine delivery system,
wherein the heat is less than 100 degrees C.; applying a voltage
bias across the substrate and the cap, wherein the voltage bias is
between 100 V and 1 kV; and applying focused energy, sourced from
one of a microwave, a laser, an infrared, and a lamp source, to at
least one of the substrate and the cap to seal the cap to the
substrate and to create vacuum in the plurality of compartments,
wherein the focused energy has a wavelength less than 600 nm.
Description
FIELD OF THE INVENTION
[0001] The present invention generally relates to bonding methods
for assembly of micromachined systems. More particularly, the
present invention relates to a low temperature anodic bonding
method using focused energy for assembly of micromachined
systems.
BACKGROUND OF THE INVENTION
[0002] Medicine delivery is an important aspect of medical
treatment. The efficacy of many medicines is directly related to
the way in which they are administered. Some therapies require that
the medicine be repeatedly administered to the patient over a long
period of time. This makes the selection of a proper medicine
delivery method problematic. Patients often forget, are unwilling,
or are unable to take their medication. Medicine delivery also
becomes problematic when the medicines are too potent for systemic
delivery. Therefore, attempts have been made to design and
fabricate a delivery device that is capable of the controlled,
periodic or continuous release of a wide variety of molecules
including, but not limited to, drugs and other therapeutics.
[0003] Micro-electro-mechanical system (MEMS) technology integrates
electrical components and mechanical components on a common silicon
substrate using microfabrication technology. Integrated circuit
(IC) fabrication processes, such as photolithography processes and
other microelectronic processes, form the electrical components.
The IC fabrication processes typically use materials such as
silicon, glass, and polymers. Micromachining processes, compatible
with the IC processes, selectively etch away areas of the IC or add
new structural layers to the IC to form the mechanical components.
The integration of silicon-based microelectronics with
micromachining technology permits complete electromechanical
systems to be fabricated on a single chip. Such single chip systems
integrate the computational ability of microelectronics with the
mechanical sensing and control capabilities of micromachining to
provide smart devices small enough to be implanted inside of a
human or animal.
[0004] Examples of implantable medicine delivery systems suitable
for fabrication using microelectro-mechanical system (MEMS)
technology are described in U.S. Pat. No. 5,366,454 (Currie, et
al.), and U.S. Pat. No. 6,123,861 (Santini, Jr., et al.). These
patents are described as improvements over non-MEMS type of
electromechanical devices that are larger and less reliable and
controlled release polymeric devices, designed to provide medicine
release over a period of time via diffusion of the medicine through
the polymer and/or degradation of the polymer over the desired time
period following administration to the patient.
[0005] U.S. Pat. No. 5,366,454 (Currie, et al.) discloses a
medication dispensing device for implantation into an animal or
human body, and including a substrate having a plurality of
compartments, a closure member, a rupturable membrane and a
membrane rupturing system. Each compartment has a charging opening
for charging the compartment with a dose of medicine and a delivery
opening permitting delivery of the medicine. The closure member,
made of silicon, is anodically bonded to the substrate, also made
of silicon, for sealing the charging openings of the compartments.
The membrane, made of silicon, may be integrally formed with the
substrate or anodically bonded to the substrate, also made of
silicon, for sealing the delivery openings of the compartments. The
membrane has a predetermined elastic deformation limit and a
predetermined rupture point. A "V-shaped" groove is formed in the
membrane to define a line of weakness to assist the rupture of the
membrane. The membrane rupturing system associated with each
compartment ruptures the membrane thereof in response to an
electrical signal. The membrane rupturing system includes a
stress-inducing member maintaining the membrane stressed to
substantially the elastic deformation limit thereof, and a
piezoelectric transducer responsive to the electrical signal for
applying to the membrane additional stress sufficient to exceed the
rupture point of the membrane, thereby causing the membrane to
rupture. Upon rupture of the membrane, body fluids are permitted to
enter into the compartment for mixing with the medicine contained
therein so that the medicine is released in admixture with the body
fluids through the delivery opening into the animal or human body.
The device further includes a control circuit connected to a power
source for supplying the electrical signal to a respective
piezoelectric transducer of each membrane rupturing system to
activate the respective piezoelectric transducer. However, a
biologically compatible polymeric film covers the membrane to bind
any broken membrane fragments to the device and to prevent the
fragments from being released into the human or animal.
[0006] U.S. Pat. No. 6,123,861 (Santini, Jr., et al.) discloses a
microchip drug delivery device for controlling the rate and time of
delivery of molecules, such as medicines, in either a periodic or
continuous manner. This device typically includes hundreds to
thousands of reservoirs, or wells, formed in a silicon substrate
containing the molecules and a release element that controls the
rate of release of the molecules. The reservoirs can contain
multiple medicines or other molecules in variable dosages. The
filled reservoirs can be capped with materials that passively
disintegrate, materials that allow the molecules to diffuse
passively out of the reservoir over time, or materials that
disintegrate upon application of an electric potential. Release
from an active device can be controlled by a preprogrammed
microprocessor, remote control, or by biosensors.
[0007] Several methods are used to bond silicon wafers together or
to other substrates, such as glass substrates, to form larger or
more complex micromachined systems, such as medicine delivery
systems, including: adhesion bonding, anodic bonding, eutectic
bonding, glass-frit bonding, fusion bonding, low temperature fusion
bonding, and microwave bonding. Among these various bonding methods
engineering tradeoffs exist for the applied temperature, applied
voltage, applied pressure, applied energy, bonding time, bond
strength, material cost, etc.
[0008] Adhesion bonding uses an adhesive to bond the substrates
together. This is typically done by spin coating a thin film of
adhesive on one or both substrates before they are brought into
contact. The substrates are typically baked at a prescribed
temperature to cure the adhesive.
[0009] Anodic bonding, otherwise known as electrostatic bonding,
typically hermetically and permanently joins glass to silicon
substrates without using adhesives. The glass substrate contains
typically has a high percentage of alkali metals, such as sodium
oxide. The silicon and glass substrates are brought into contact
with each other. The silicon and glass substrates are heated to a
temperature (typically in the range 300-500.degree. C. depending on
the glass type) above the softening point of the glass substrate
that results in the sodium oxide splitting up into sodium and
oxygen ions. A high DC voltage (e.g., up to 1 kV) is applied across
the substrates creating an electrical field that penetrates the
substrates. The electric field causes the sodium ions to migrate
from the interface between the substrates towards the cathode where
they are neutralized providing a depletion layer with high electric
field strength. The resulting electrostatic attraction at the
depletion layer brings the silicon and glass into intimate contact.
The electric field also causes the oxygen ions to flow from the
glass substrate to the silicon substrate resulting in an anodic
reaction at the interface with the silicon ions in the silicon
substrate to form irreversible silicon-oxygen-silicon bonds. The
result is that the glass substrate is bonded to the silicon
substrate with a permanent chemical bond. The disadvantages of
anodic bonding include the relatively high temperature required,
temperature non-uniformity during vacuum sealing, and relatively
long bond times (e.g., 10 minutes).
[0010] Eutectic bonding and glass-frit bonding use a film of metal
and glass ceramic adhesive, respectively, to hermetically seal the
substrates together under high temperature.
[0011] Fusion bonding uses two silicon substrates having
hydrophobic or hydrophilic, mirror-polished, flat and clean
surfaces. The two surfaces of the substrates contact each other
under high pressure creating atomic attraction forces that bond the
two substrates together. The atomic attraction forces are strong
enough to allow the bonded substrates to be moved to a furnace. The
bonded substrates are annealed at high temperature (e.g.,
900.degree. C.-1100.degree. C.) in the furnace to form a solid
hermetic seal between the two substrates.
[0012] Low temperature fusion bonding advances the glass-frit
bonding process. In contrast to the glass-frit bonding process, low
temperature fusion bonding does not use a glass ceramic adhesive to
bond the substrates together. The low temperature fusion bonding
process uses low heat to soften the substrates, and pressure to
squeeze and hold the substrates together until they bond over a
prescribed period of time.
[0013] Microwave bonding uses electromagnetic energy to bond two
metallized dielectric or silicon substrates to each other. The
electromagnetic energy in the form of a pulse heats the metallic
interface between the two substrates to melt the interface together
while permitting the substrates to remain cool.
[0014] It would be desirable to have a medicine delivery system,
adapted to be implanted in a human or animal, that actively
releases a drug or other molecule into the animal or human by
rupturing a membrane, without permitting the ruptured membrane to
separate from the medicine delivery system and to be released in
the animal or human. Such a system would not permit disintegrated
membrane material to separate from the drug delivery device and to
be released in the animal or human, as disclosed in U.S. Pat. No.
6,123,861 (Santini, Jr., et al.). Further, such a system would not
require the biologically compatible polymeric film shown as
necessary by U.S. Pat. No. 5,366,454 (Currie, et al.) to bind any
broken membrane fragments to the device and to prevent the
fragments from being released into the human or animal.
[0015] It would also be desirable to have a bonding process to
hermetically seal two substrates together at a temperature lower
than the 300-500.degree. C. range used for anodic bonding. Such a
bonding process would not damage thermally degraded materials, like
the medicine in the medication dispensing device disclosed in U.S.
Pat. No. 5,366,454 (Currie, et al.). Such a bonding process would
also be fast to provide high manufacturing throughput. Further,
such a process would also apply a relatively low pressure to the
substrates.
SUMMARY OF THE INVENTION
[0016] According to one aspect of the present invention, a bonding
process seals two substrates together at a relatively low
temperature.
[0017] According to another aspect of the present invention, the
bonding process seals the two substrates together at a relatively
low voltage.
[0018] According to another aspect of the present invention, the
bonding process seals the two substrates together at a relatively
low pressure.
[0019] According to another aspect of the present invention, the
bonding process seals the two substrates together at a relatively
high speed.
[0020] According to another aspect of the present invention, the
bonding process hermetically and vacuum seals the two substrates
together.
[0021] According to another aspect of the present invention, the
bonding process seals the two substrates together using a
combination of anodic bonding and focused energy bonding.
[0022] According to another aspect of the present invention, a
method bonds substrates in a micromachined system. A first
substrate and a second substrate are provided. The first substrate
is placed in contact with the second substrate. Heat is applied to
the micromachined system. A bias voltage bias is applied across the
first substrate and the second substrate. Focused energy is applied
to at least one of the first substrate and the second substrate to
seal the first substrate to the second substrate.
[0023] These and other aspects of the present invention are further
described with reference to the following detailed description and
the accompanying figures, wherein the same reference numbers are
assigned to the same features or elements illustrated in different
figures. Note that the figures may not be drawn to scale. Further,
there may be other embodiments of the present invention explicitly
or implicitly described in the specification that are not
specifically illustrated in the figures and vice versa.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] FIG. 1 illustrates a perspective view of a medicine delivery
system, including a control unit and a plurality of medicine
delivery units, in accordance with a preferred embodiment of the
present invention.
[0025] FIG. 2 illustrates a magnified partial top plan view of the
medicine delivery system of FIG. 1.
[0026] FIG. 3 illustrates a magnified top plan view of a medicine
delivery unit, as shown in FIGS. 1 and 2, having a release element
disposed on a membrane.
[0027] FIG. 4 illustrates a magnified lateral cross-sectional view
of the medicine delivery unit taken along line 4-4 in FIG. 3.
[0028] FIG. 5 illustrates a longitudinal cross-sectional view of
the medicine delivery unit taken along line 5-5 in FIG. 3, before
the membrane is ruptured.
[0029] FIG. 6 is a longitudinal cross-sectional view similar to
FIG. 5 but shows the medicine delivery unit after the membrane is
ruptured.
[0030] FIGS. 7A-7K illustrate, in a sequence of steps, a MEMS
fabrication process for making the medicine delivery unit, as shown
in FIGS. 1-6, in accordance with the preferred embodiment of the
present invention.
[0031] FIG. 8 illustrates a flowchart describing a method for
sealing the medicine delivery unit, as shown in FIGS. 1-6, in
accordance with the preferred embodiment of the present
invention.
[0032] FIG. 9 illustrates a block diagram of the control unit and
the medicine delivery units, as shown in FIGS. 1 and 2, in
accordance with the preferred embodiment of the present
invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0033] FIG. 1 illustrates a perspective view of a medicine delivery
system 10, including a control unit 12 and a plurality of
spaced-apart medicine delivery units 14, in accordance with a
preferred embodiment of the present invention. The medicine
delivery system 10 is fabricated using the MEMS technology, as
described above, using methods commonly applied to the manufacture
of integrated circuits such as ultraviolet (UV) photolithography,
reactive ion etching, and electron beam evaporation, as are well
known in the art. The MEMS technology fabrication procedure permits
the manufacture of medicine delivery systems 10 with primary
dimensions (length of a side if square or rectangular, or diameter
if circular) ranging from less than a millimeter to several
centimeters. The thickness of a typical medicine delivery system 10
is 300 micrometers, but can vary from approximately 10 micrometers
to several millimeters, depending on the system's application.
Changing the system thickness affects the maximum number of
medicine delivery units 14 that may be incorporated into the system
and the volume of each medicine delivery unit 14. "In body"
applications of the device would typically require systems having a
primary dimension of 2 cm or smaller. Systems for in body
applications are small enough to be swallowed or implanted using
minimally invasive procedures. Smaller in body systems (on the
order of a millimeter) can be implanted using a catheter or other
injection means.
[0034] Preferably, the medicine delivery system 10 has a small
wafer-like substrate 16 providing the plurality of spaced-apart
medicine delivery units 14. The substrate 16 serves as a support
for the medicine delivery device 10. The substrate 16 may be any
material that is suitable for etching or machining, for providing a
support, and is impermeable to medicines and to surrounding body
fluids, such as, water, blood, electrolytes or other solutions.
Examples of materials, suitable for the substrate 16, include,
without limitation, ceramics, semiconductors, glass, and degradable
and non-degradable polymers.
[0035] Biocompatibility of the substrate material is preferred, but
not required. For in body applications, non-biocompatible materials
may be encapsulated in a biocompatible material, such as
poly(ethylene glycol) or polytetrafluoroethylene-like materials,
before use. Silicon is an example of a material that forms a
strong, non-degradable, easily etched substrate that is impermeable
to the enclosed medicines and the surrounding body fluids.
Poly(anhydride-co-imide) is an example of a material that forms a
strong substrate that degrades or dissolves over a period of time
into biocompatible components. This material is preferred for in
body applications where the system is implanted and physical
removal of the device at a later time is not feasible or
recommended.
[0036] Each medicine delivery unit 14 has a compartment 18, adapted
to contain or enclose a medicine 34 (shown in FIGS. 4-7), which is
defined by a cavity, a recess, or a reservoir formed in the
substrate 16 by etching, machining, or other known process. The
compartments 18 are each provided with a charging opening 20
permitting receipt of medicine 34 in the compartment 18, and with a
delivery opening 22 permitting delivery of the medicine contained
therein. A cap 24 seals the charging openings 20, preferably using
a bonding method described in FIG. 8, or a waterproof epoxy or
other appropriate material impervious to the surrounding fluids. A
membrane 26 seals the delivery openings 22.
[0037] As best seen in FIG. 4, the medicine 34 is inserted into the
charging opening 20 of the compartment 18 by any method including,
without limitation, injection, inkjet printing, spin coating,
capillary action, pulling or pushing the medicine using a vacuum or
other pressure mechanism, melting the material into the compartment
18, centrifugation and related processes, packing solids into the
compartment 18, or any combination of these or other similar
filling techniques.
[0038] The medicine 34 may be a solid, liquid or gel in the
compartments 18. Preferably, the medicine 34 is formed as a solid
because the solid medicine has a high concentration per unit
volume, such as for example in the pico-gram range. The medicine 34
may be any natural, synthetic, or semi-synthetic compound or
mixture thereof that can be delivered. In one embodiment, the
medicine delivery system 10 is used to deliver medicines
systemically to a patient in need thereof. In another embodiment,
the construction and placement of the medicine delivery system 10
in a patient enables the localized release of medicines 34 that may
be too potent for systemic delivery. As used herein, medicines are
compounds or salts, prodrugs, solvates, salts and/or solvates of
prodrugs thereof, including, without limitation, proteins, nucleic
acids, polysaccharides and synthetic organic molecules, having a
bioactive effect, for example, anesthetics, vaccines,
chemotherapeutic agents, hormones, metabolites, sugars,
immunomodulators, antioxidants, ion channel regulators, and
antibiotics. The medicines 34 can be in the form of a single
medicine or medicine mixtures and can include pharmaceutically
acceptable carriers. In another embodiment, molecules are released
in body in any system where the controlled release of a small
(milligram to nanogram) amount of one or more molecules is
required, for example, in the fields of analytic chemistry or
medical diagnostics. Molecules can be effective as pH buffering
agents, diagnostic agents, and reagents in complex reactions such
as the polymerase chain reaction or other nucleic acid
amplification procedures.
[0039] Each compartment 18 may contain different medicines 34
depending on the medical needs of the patient or other requirements
of the medicine delivery system 10. For applications in medicine
delivery, for example, the medicines 34 in each of the rows can
differ from each other. Further, the rate of the release of the
medicine 34 may differ within each row to release a medicine at a
fast rate from one compartment 18 and a slow rate from another
compartment 18. Each compartment 18 may also contain different
dosages of the medicines 34. The dosages may also vary within each
row of medicine delivery units 14.
[0040] For in body applications, the entire medicine delivery
system 10, except for the side of the medicine delivery system 10
providing the delivery openings 22 on the medicine delivery units
14, is encased in a material appropriate for the system 10. For in
body applications, the medicine delivery system 10 is preferably
encapsulated in a biocompatible material such as poly(ethylene
glycol) or polytetrafluoroethylene.
[0041] Use of MEMS technology fabrication techniques permit the
incorporation of hundreds to thousands of compartments 18 in a
single medicine delivery system 10. The spacing between each
compartment 18 depends on its particular application and whether or
not the release of the medicine is active or passive. With an
active release, the distance between the reservoirs may be slightly
larger (between approximately 1 and 10 micrometer) than with a
passive release due to the space occupied by a release element (not
shown in FIG. 1) on or near each compartment 18. The compartments
18 may be made in nearly any shape and depth, and need not pass
completely through the substrate 16. In a preferred embodiment, the
compartments 18 are etched into a silicon substrate by potassium
hydroxide in the shape of a square pyramid, having side walls
sloped at approximately fifty-four degrees, which pass completely
through the substrate (approximately 300 micrometers) to the
membrane 26 on the other side of the substrate 16, as shown in FIG.
7. The pyramidal shape permits easy filling of the compartments 18
through the charging opening 20 (approximately 500 micrometers by
500 micrometers) on a patterned side of the substrate 16, release
through the delivery opening 22 (approximately 50 micrometers by 50
micrometers) on the other side of the substrate 16, and provides a
large cavity inside the medicine delivery unit 14 for storing the
medicine.
[0042] Referring next to FIGS. 2-6, FIG. 2 illustrates a magnified
partial top plan view of the medicine delivery system 10, of FIG.
1. FIG. 3 illustrates a magnified top plan view of a medicine
delivery unit 14, as shown in FIGS. 1 and 2, having a release
element 28 disposed on the membrane 26. FIG. 4 illustrates a
magnified lateral cross-sectional view of the medicine delivery
unit 14, as shown in FIG. 3, having the release element 28 disposed
on the membrane 26. FIG. 5 illustrates a longitudinal elevation
view of the medicine delivery unit 14, as shown in FIG. 3, before
the membrane 26 is ruptured, in accordance with the preferred
embodiment of the present invention. FIG. 6 illustrates the
longitudinal elevation view of the medicine delivery unit 14, as
shown in FIG. 3, after the membrane 26 is ruptured, in accordance
with the preferred embodiment of the present invention.
[0043] The release element 28 is associated with each medicine
delivery unit 14 for rupturing the membrane 26 in response to a
control signal 78 (shown in FIG. 9) from the control unit 12. The
size, shape and placement of the release element 28 may vary,
depending on various engineering considerations for the particular
application. The release element 28 is preferably disposed on the
membrane 26, either inside and/or outside the compartment 18, using
deposition techniques such as chemical vapor deposition, electron
or ion beam evaporation, sputtering, spin coating, and other
techniques known in the art. Various release elements may be used
to rupture the membrane 26 including, without limitation,
electrostatic, magnetic, piezoelectric, bimorph, shape memory
alloys, temperature, chemical, and other mechanisms that cause
stress or strain on the membrane 26.
[0044] When a temperature element such as a polysilicon
piezoresistor is used as the release element 28 a thermal
insulator, such as silicon dioxide, may be used as the membrane 26
to isolate the temperature element from the medicine 34, if
desired. The substrate 16 is preferably formed of silicon and acts
as a heat sink. The thermal conductivity for silicon is 1.57
W/cm-degrees C., for silicon dioxide is 0.014 W/cm-degrees C., and
for polysilicon is 0.17 W/cm-degrees C. When the temperature
element 28 is heated, the membrane 26 cracks due to the high
thermal gradient induced stresses on the membrane 26 causing the
medicine delivery unit 14 to open. A thin film of tensile silicon
nitride may be applied to the membrane 26 to assist in opening the
medicine delivery unit 14 when the temperature element is heated.
After the membrane 26 is ruptured, the tensile silicon nitride
pulls the membrane 26 back to assist in forming the delivery
opening 22.
[0045] The release element 28 is electrically coupled to the
control unit 12 via electrodes 30 and 32. Exemplary conductive
materials for the electrodes include metals such as copper, gold,
silver, and zinc and some polymers. Typical film thickness of the
electrodes 30 and 32 may range from 0.05 to several microns. When
an electric potential is applied to the electrodes 30 and 32, the
membrane 26 ruptures along a predetermined pattern to expose the
compartment 18 containing the medicine 34 to the surrounding
fluids.
[0046] The predetermined rupture pattern preferably approximates
the size and shape of the release element 28. Preferably, the
predetermined rupture pattern has a width in the range of 2 to 20
micrometers, a length of a side of the delivery opening 22 in the
range of 40 to 500 micrometers, and spacing between the
predetermined rupture pattern and the edge of the delivery opening
22 in the range of 2 to 20 micrometers.
[0047] An insulating or dielectric material 40 such as silicon
oxide (SiO.sub.2) or silicon nitride (SiN.sub.2) is deposited over
the entire surface of the medicine delivery system 10 by methods
such as chemical vapor deposition, electron or ion beam
evaporation, sputtering, or spin coating and other techniques known
in the art. Photoresist (not shown) is patterned on top of the
dielectric material 40 to protect it from etching except on the
release element 28 directly over each compartment 18. The
dielectric material 40 can be etched by plasma, ion beam, or
chemical etching techniques. The purpose of this dielectric
material 40 and photoresist film is to protect the electrodes 30
and 32 from corrosion, degradation, or dissolution in all areas
where electrode film removal is not necessary for release of the
medicine 34.
[0048] The membrane 26 has a predetermined elastic deformation
limit and a predetermined rupture point. The membrane 26 may be
formed of a variety of materials including, without limitation,
dielectric, polysilicon or silicon. The membrane 26 may have a line
of weakness formed therein along the predetermined rupture pattern
to assist with rupturing the membrane 26. Preferably, the membrane
26 is thinner at the line of weakness than at other areas of the
membrane 26. Such thinning may be formed by a V-shaped indentation
in the membrane 26. Preferably, the membrane 26 is integrally
formed with the substrate 16. Alternatively, the membrane 26, can
be formed separately from the substrate 16 and bonded thereto, such
as with a membrane, formed of silicon, anodically bonded to a
substrate 16, also formed of silicon.
[0049] Preferably, the membrane 26 is hermetically sealed over the
delivery openings 22 to form a vacuum in the compartments 18.
Various mechanisms for forming the vacuum seal include, without
limitation, wide area heating mechanisms such as electrostatic
bonding, and local area heating sources such as laser, microwave,
and infrared energy. The local area heating mechanisms are
preferred over the wide area heating mechanisms because the local
area heating mechanisms operate at a lower temperature (e.g.,
100-150 degrees C.) rather than at a higher temperature (e.g.,
300-400 degrees C.). Using the lower temperature over the local
area prevents damage to the medicine delivery unit 10 and to the
medicine 34, and creates more strain on the membrane 26 due to the
high temperature gradient along the membrane 26 from the local area
to the center of the membrane 26. In this case, each compartment 18
is drawn under a vacuum causing the membrane 26 to be drawn inward
into the compartment 18 forming a concave shape. Under the vacuum,
the membrane 26 is strained to a point near to but less than the
predetermined elastic deformation limit and the predetermined
rupture point of the membrane 26. Since the compartment 18 is under
vacuum, the membrane 26 is in a pre-stressed condition. The release
element 28 causes the membrane 26 to bend past its yield point
resulting the membrane 26 rupturing along the predetermined
pattern. Because the membrane 26 is already in a pre-stressed
state, the release element 28 does not require as much energy to
rupture the membrane 26, as compared to a membrane 26 that is not
in a pre-stressed state.
[0050] The membrane 26 has a first portion 35 located inside the
predetermined pattern and a second portion 37 located outside the
predetermined pattern. The first portion 35 of the membrane 26 is
attached to the second portion 37 of the membrane 26 at a
connection area 39. In the preferred embodiment of the present
invention, the first portion 35 of the membrane 26 forms a lid and
the connection area 39 forms a hinge 36. When the membrane 26
ruptures, the lid separates from the second portion 37 of the
membrane 26, except at the hinge 36, to permit the medicine 34 to
be delivered through the delivery opening 22, as shown in FIG. 6.
The hinge 36 permits the lid to remain attached to the medicine
delivery system 10 so that it is not released in the animal or
human. The first portion 35 of the membrane 26 and the connection
area 39 may have various sizes, shapes and positions, depending on
various engineering considerations for a particular
application.
[0051] FIGS. 7A-7K illustrate, in a sequence of steps, a MEMS
fabrication process for making the medicine delivery unit 14, as
shown in FIGS. 1-6, in accordance with the preferred embodiment of
the present invention. FIG. 7A illustrates the step of providing
the substrate 16. FIG. 7B illustrates the substrate 16 having the
membrane 26 applied to each opposite side of the substrate 16. In
FIG. 7C, material 38 for the release element 28 is applied to the
membrane 26 on one side of the substrate 16. In FIG. 7D, the
material 38 for the release element 28 is selectively removed to
form the release element 28. In FIG. 7B, the insulator 40 is
selectively applied to the membrane 26 and the membrane material on
the bottom side of the substrate 16 is selectively removed. In FIG.
7F, the medicine delivery unit 14 is turned over 180 degrees,
either physically or for the sake of illustration. In FIG. 7G, the
substrate 16 is etched or machined between the remaining portions
of the membrane material to form the compartment 18 and the
charging opening 20. In FIG. 7H, the remaining portions of the
membrane material are removed. Alternatively, the remaining
portions of the membrane material stay depending on the type of
material. In FIG. 7I, the compartment 18 is filled with the
medicine 34. In FIG. 7J, the cap 24 is disposed over the
compartment 18 to seal the charging opening 20 under vacuum,
according to the method 60 described in FIG. 8. In FIG. 7K, the
medicine delivery unit 14 is again turned over 180 degrees, either
physically or for the sake of illustration.
[0052] FIG. 8 illustrates a flowchart describing a method 60 for
sealing the medicine delivery unit 10, as shown in FIGS. 7A-7K. The
method 60 starts at step 61. At step 62, the method 60 provides the
substrate 16, having the compartments 18, and the cap 24 in an
appropriate manner for high volume manufacturing. At step 63, the
method 60 charges the compartments 18 with the medicine 34, as
describe above. At step 64, the method 60 covers the compartments
18 with the cap 24, as described above. At step 65, the method 60
applies heat 58 to the medicine delivery system 10. In the
preferred embodiment of the present invention the heat is less than
100 degrees C., which is much less than the 300-500 degrees C.
temperature range used for traditional anodic bonding. At step 66,
the method 60 applies a voltage bias 56 across the substrate 16 and
the cap 24. Preferably, a positive voltage is applied to the cap 24
and a negative voltage is applied to the substrate 16.
Alternatively, the positive and negative voltages may be reversed,
depending on the materials of the cap 24 and the substrate 16. In
the preferred embodiment of the present invention, the voltage bias
56 is greater than 100 V and less than the 1 kV used for
traditional anodic bonding. At step 67, the method 60 applies
focused energy 54 to the cap 24 to seal the cap 24 to the substrate
16 and to create a vacuum in the compartments 18. The focused
energy 54 includes, without limitation, microwave, laser, infrared,
lamps, and the like. The focused energy 54 couples into the cap 24
(e.g., at a wavelength less than 600 nm) to raise the temperature
in a local area over one or more compartments 18 for the duration
of an energy pulse having a microsecond to millisecond time
duration. Such fast heat coupling assists in bonding the interface
between the cap 24 and the substrate 16, without damaging the cap
24, the substrate 16, or the medicine 34. Silicon material conducts
heat quickly and glass material and a vacuum conducts heat slowly.
Therefore, when the cap 24 is made of silicon and the substrate 16
is made of glass, the focused energy 54 conducts slowly to the
medicine 34. Note that the focused energy 54 does not necessarily
need to be aligned with particular features of the medicine
delivery system 10, depending on the size of the features, the
power level and time duration of the focused energy. At step 68,
the method 60 ends. Although, the method 60 describes a bonding
process for assembly of the medicine delivery system 10, the method
may be used for any kind of micromachined system or device.
[0053] The benefits of the bonding process described in the method
60 include: a fast manufacturing throughput, uniform seals, no
damage to the medicine 34, a low bonding temperature permitting
more design flexibility and stable mechanical dimensions with
temperature, a flat assembly process, no measurable flow of the
glass material permitting sealing around previously machined
grooves, cavities etc. without any loss of dimensional tolerances,
parasitic capacitances are kept extremely small because the glass
material is an insulator, the bonding process may be performed in
vacuum permitting hermetically sealed reference cavities to be
formed, transparency of the glass at optical wavelengths permits
simple, but highly accurate, alignment of pre-patterned glass and
silicon wafers as well as to observe the inside of micro-fluidic
devices, a high yield process that is tolerant to particle
contamination and wafer warp because the electrostatic field
generates a high clamping force which overcomes surface
irregularities, a low cost wafer scale process for first order
packaging can be done at a chip level if required, multi-layer
stacks permit easy routing to complex 3-D microstructures, and a
high strength bond that is higher than the fracture strength of the
glass material.
[0054] FIG. 9 illustrates a block diagram of the control unit 12
and the medicine delivery units 14, as shown in FIGS. 1 and 2, in
accordance with the preferred embodiment of the present invention.
The medicine delivery system 10 accurately delivers medicine 34 at
defined rates and times according to the needs of a human or animal
patient or other experimental system. The control unit 12 includes
a controller 70, a memory 72, a sensor 15, a power supply 74, and a
demultiplexer 76. Preferably, the control unit 12 is constructed as
an integrated circuit, but may be constructed as discrete circuits.
The control unit 12 may have internal or external memory, such as
RAM and/or ROM.
[0055] The power supply 74 provides power to the appropriate
functions in the control unit 12, such as the controller 70.
Preferably, the power supply 74 is a battery to permit portable or
in body applications, and is preferably a thin film electrochemical
cell deposited on the substrate 16. The criteria for selection of
the power supply are small size, sufficient power capacity, ability
to be integrated into the control unit 12, and, in some
applications, the ability to be recharged and the length of time
before recharging is necessary. Alternative batteries of this type
include lithium-based, rechargeable micro-batteries that are
typically only ten microns thick and occupy 1 cm.sup.2 of area. One
or more of these batteries can be incorporated directly into the
control unit 12.
[0056] The controller 70 generates the control signal 78 to control
the medicine delivery units 14. The control signal 78 may be
carried on a single line carrying multiple signals, wherein each of
the multiple signals is associated with a corresponding medicine
delivery unit 14. Alternatively, the control signal may be carried
on a plurality of lines, wherein each of the plurality of lines is
associated with each medicine delivery unit 14. Hence, the
controller 70 in combination with the control signal 78 actively
controls the rupturing of the membrane 26 for each medicine
delivery unit 14.
[0057] The control unit 12 is designed based on the period over
which the medicine delivery is desired, generally in the range of
at least three to twelve months for in body applications. In
contrast, release times as short as a few seconds may be desirable
for some applications. In some cases, continuous (constant) release
from the compartment 18 may be most useful. In other cases, a pulse
(bulk) release from the compartment 18 may provide more effective
results. Note that a single pulse medicine delivery from one
compartment 18 can be transformed into a multiple pulse medicine
delivery by using multiple compartments 18. In addition, delivering
several pulses of medicines in quick succession can simulate
continuous medicine delivery.
[0058] The controller 70 controls the time and rate of delivery of
the medicine 34 from each compartment 18 responsive to a software
program or circuit, remote control, a signal from a sensor, or by
any combination of these methods. Preferably, the controller 70 is
used in conjunction with the sensor 15, the memory 72, the power
supply 74, and the demultiplexer 76. The software program stored in
the memory 72 determines the time and rate of medicine delivery.
The memory 72 sends instructions to the controller 70. When the
time for release has been reached as indicated by the software
program, the controller 70 sends the control signal 78
corresponding to the address (location) of a particular compartment
18 to the demultiplexer 76. The demultiplexer 76 generates an
electrical signal to the particular compartment 18 addressed by the
controller 70.
[0059] The sensor 15 advantageously provides a closed loop feedback
system to permit the medicine delivery system 10 to vary the time,
rate and/or dosages of the medicine responsive to monitored
conditions in the environment, such as the human or animal
body.
[0060] The medicine delivery system 10 has numerous applications.
The medicine delivery system 10 can be used to deliver small,
controlled amounts of chemical reagents or other molecules to
solutions or reaction mixtures at precisely controlled times and
rates. Analytical chemistry and medical diagnostics are examples of
fields where the medicine delivery system 10 can be used. The
medicine delivery systems 10 can be implanted into a patient,
either by surgical techniques or by injection, or can be swallowed.
The medicine delivery systems 10 provide delivery of medicines to
animals or persons who are unable to remember or be ambulatory
enough to take medication. The medicine delivery systems 10 further
provide delivery of many different medicines at varying rates and
at varying times of delivery.
[0061] Hence, while the present invention has been described with
reference to various illustrative embodiments thereof, the present
invention is not intended that the invention be limited to these
specific embodiments. Those skilled in the art will recognize that
variations, modifications and combinations of the disclosed subject
matter can be made without departing from the spirit and scope of
the invention as set forth in the appended claims.
* * * * *