METHODS FOR FABRICATING MICRO-DEVICES
20170043147 ยท 2017-02-16
Inventors
Cpc classification
B81C1/00119
PERFORMING OPERATIONS; TRANSPORTING
B81B7/008
PERFORMING OPERATIONS; TRANSPORTING
B81C1/00341
PERFORMING OPERATIONS; TRANSPORTING
B82Y5/00
PERFORMING OPERATIONS; TRANSPORTING
B81C1/00246
PERFORMING OPERATIONS; TRANSPORTING
Y10T29/49124
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
B81B2201/058
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502707
PERFORMING OPERATIONS; TRANSPORTING
International classification
A61M37/00
HUMAN NECESSITIES
B81C1/00
PERFORMING OPERATIONS; TRANSPORTING
Abstract
The present invention provides methods utilizing current nano-technological processes for fabricating a range of micro-devices with significantly expanded capabilities, unique functionalities at microscopic levels, enhanced degree of flexibilities, reduced costs and improved performance in the fields of bioscience and medicine. Such fabricated micro-devices have significant improvements in many areas over the existing, conventional methods, which include, but are not limited to reduced overall costs, early disease detection, targeted drug delivery, targeted disease treatment and reduced degree of invasiveness in treatment.
Claims
1. A method of fabricating a micro-device for biological and medical applications, wherein the method uses microelectronics processes and comprises: using at least one movable material and at least one structural material; and forming at least one component which can move upon receiving a force or energy.
2. The method of claim 1, wherein said movable material and said structural materials are joined with at least one space material.
3. A method of fabricating a micro-device for biological and medical applications, wherein the method uses microelectronics processes and comprises the following steps: fabricating a integrated circuit containing memory and logic functions for data storage, data analysis, data comparison, data processing, and/or decision making purposes; fabricating a micro-injector; and fabricating a micro-container.
4. The method of claim 3, further comprising the step of fabricating a signal receiver, a signal transmitter, a micro-sensor, a micro-positioning sensor, or a micro-motion apparatus which comprises a micro-motor, micro-propeller, or micro-stepper.
5. The method of claim 3, further comprising the following steps: fabricating a signal receiver; fabricating a signal transmitter; fabricating a micro-sensor; fabricating a micro-motion apparatus comprising of micro-motor, micro-propeller, and micro-stepper; and fabricating a micro-positioning sensor.
6. The method of claim 3, wherein the injection function is accomplished by means comprising hydraulic, electrical, electro-mechanical, electro-magnetic, capacitive, micro-electro mechanical, or piezoelectric force.
7. The method of claim 3, wherein the technology for constructing an integrated circuit comprises complementary metal-oxide-semiconductor (CMOS) technology or bipolar complementary metal-oxide-semiconductor (BiCMOS) technology.
8. The method of claim 3, wherein each injector is optionally connected to an integrated circuit on the micro-device and can be selected to turn on injection action to release compound.
9. The method of claim 3, wherein said micro-containers have means to release stored compound in a timed manner.
10. The method of claim 3, wherein said timed manner in compound release is achieved using a method selected from the following: using a desired thickness of bio-degradable capping layer at the surface of said micro-containers, receiving instructions from integrated circuit on the same micro-device, and means for receipt of a wireless signal from a computer.
11. The method of claim 3, wherein said micro-container carries one or a combination of the following: a cancer killing drug; a cancer killing protein; a cancer killing signal; a signal which stimulates immune system against cancer; a signal which alerts immune system; a species which carry electrical signal; an agent disrupting response from cancer cells and system; an agent suppressing transfer of cancer cells, proteins, tissue, signal and response, hormones; a catalyst; a messenger RNA; a receptor; natural or synthesized human cells; natural or synthesized human proteins capable of killing tumors and triggering resistance to cancers; a Type II Interferon; a platinum-based cancer drug; sirt1 enzyme; resveratrol; and tumor necrosis factors (TNFs) for improved treatment effects.
12. The method of claim 3, wherein said substrate comprises a silicon substrate.
13. The method of claim 3, wherein the microelectronics process comprises thin film deposition, lithography, wet etch, dry etch, cleaning, wet processing, diffusion, ion implantation, annealing, or CMP.
14. The method of claim 3, wherein said micro-device is fabricated on a wafer substrate, which can be cut and packaged into desired sizes with a desired number and combinations of types of micro-devices on each of packaged final block.
15. The method of claim 3, wherein said spacial region, said moving component, said micro-container, and said micro-injector each have a size from 0.05 micron to 1 centimeter, and a minimum feature from 0.01 micron to 20 microns.
16. The method of claim 15, wherein said spacial region, said moving component, said micro-container, and said micro-injector each have a size from 0.1 micro to 5 millimeter, and minimum feature from 0.01 micron to 0.5 micron.
17. The method of claim 3, wherein said micro-device carries one or a combination of the following: a cancer killing drug, a cancer killing protein, a cancer killing signal, a signal which stimulates immune system against cancer, a signal which alerts immune system, a species which carry electrical signal, an agent disrupting response from cancer cells and system, an agent suppressing transfer of cancer cells, proteins, tissue, signal and response, and virus.
18. The method of claim 3, wherein said micro-devices optionally have bio-degradation functions and capabilities.
19. The method of claim 3, wherein said micro-devices optionally have disintegration capabilities and decompose into pieces with sizes smaller than 1 micron.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] These and other features, aspects and advantages of the present invention will become better understood with regard to the following description, appended claims and accompanying drawings where:
[0019]
[0020]
[0021]
[0022]
[0023]
[0024]
[0025]
DETAILED DESCRIPTION OF THE INVENTION
[0026] While major progress in the area of bio-medicine has been made in the past few decades, in a number of key areas including deadly disease (such as cancer) prevention, early detection and treatment, progress has been relatively slow. For example, to date, treatment options for cancer have remained mainly limited to chemotherapy, radiation treatment or a combination of the two. On the other hand, some progress has been made in the area of cancer curing drugs, including a targeted drug approach. However, drugs that have shown promise during animal testing have not performed as expected during clinical human trials. Often, drugs lack effectiveness, selectivity, specificity, have side effects and high costs. A new approach and major innovation is urgently needed to address these major issues. In this invention, a set of novel process flows utilizing microelectronics processes to fabricate powerful micro-container/injectors with other optional components integrated onto integrated circuits for improved drug and other agent transportation and delivery with improved effectiveness, selectivity and specificity with reduced side effects and costs. A novel use of these devices is further disclosed herein.
[0027] While microelectronics process technology has been utilized to fabricate a wide range of information technology-related products such as memory devices, micro-processors, and digital signal processors, relatively speaking, its application in the field of bio-medicine is still in its infancy. To date, the application of microelectronics process technologies has been mainly limited to chips for lab tests such as DNA mapping and the diagnosis of certain diseases. Such chips contain integrated, miniaturized probes to speed up tests and data collection. However, to a large extent, its (microelectronics) application and associated special fabrication process flows for more sophisticated bio-medical applications have not been developed.
[0028] The key inventive aspect of this patent application is a set of novel process flows using microelectronics processes for fabricating micro-devices comprising at least a sealed space and a micro-component which can convert an applied force or energy into a motion, where a portion of the wall of said sealed space is a part of said micro-component. The microelectronics process includes, but is not limited to, thin film deposition, lithography, wet etch, dry etch, cleaning, wet processing, diffusion, ion implantation, annealing and CMP.
[0029] One embodiment is the fabrication process of micro-containers and micro-injectors for bio-medical applications with significantly improved drug carrying flexibility, selectivity, specificity, efficiency, and reduced side effects and costs.
[0030] Another key, novel aspect of the current invention is the fabrication process flow to integrate micro-injectors and micro-containers with an injection action from the said injector to release drug(s) or agent(s) contained in the micro-containers.
[0031] Yet another novel feature of this disclosure is the integration of micro-containers, injectors, and other components which include, but is not limited to, sensors, position sensors, signal transmitters, signal receivers and motion apparatus (such as motorized propellers and steppers) with integrated circuits onto the same micro-device. These features use processing technologies which include, but are not limited to CMOS or BiCMOS technologies with both memory and logic functions. The integration of the above components can greatly enhance performance of the micro-devices for bio-medical applications, with both mechanical abilities as well as device motion, position, signal sensing, signal transmission, data storage, data analysis, data processing and logic decision-making capabilities.
[0032] One additional innovative aspect of the current application is the ability to select micro-containers for drug (or agent) release through a pre-programmed instruction set or instructions from an integrated circuit on the micro-device or a host computer via wireless signal instructions to the corresponding, selected micro-device.
[0033] Another embodiment is the process flow and design using a bio-compatible material with dissolution ability in a desired environment, as a capping layer for micro-containers for timed drug or carrying agent release.
[0034] Still, another embodiment is the use of micro-containers/injectors for carrying natural and/or synthesized cells, proteins, biological, chemical, and electrical species for disease prevention and treatment. The agents carried are not limited to drugs. The agents could be species carrying biological signal information and immunity triggering agents, hormones, catalysts, messenger RNA, receptors such as G protein linked receptors, which have improved speed and efficiency. For example, for cancer prevention and treatment, natural tumor killing or signal carrying cells/proteins can be carried to further efficiency and speed (such as CD8 T cells, NK cells, Type II Interferons, and TNFs).
[0035] In this invention disclosure, the micro-devices include, but are not limited to, micro-containers and micro-injectors for drug delivery and disease treatments. Other components include sensors, signal transmitters, signal receivers and motorized propellers. The components/devices can be integrated onto integrated circuits with both memory and logic functions. The said microelectronics processes include, but are not limited to, thin film deposition, lithography, etch (both wet and dry etch processes), cleaning, wet processing, diffusion, ion implantation and CMP processes. Such processes are utilized and arranged in many novel ways to fabricate various types of micro-devices with a minimum feature size of as small as 0.1 micron. The above-mentioned micro-devices have one to multiple functions, with typical sizes ranging from sub-micron to several millimeters. Optionally, the said devices are bio-degradable, or capable of disintegrating into smaller pieces on the order of less than 10 microns.
[0036]
[0037] In addition to the above process flow illustrated in
[0038]
[0039] The above three examples show several novel process flows using microelectronics process technologies for fabricating micro-containers with compound such as drug carrying capabilities for bio-medical applications. The dimensions for an individual micro-container can range from 0.05 micron to 5 millimeters in size (diameter and height), with a minimum feature size (for example, for micro-container nozzle size) of 0.05 micron to 20 microns being preferred.
[0040] In addition to carrying a desired compound or compounds to a targeted location, when and how the said compound(s) are released is also critical for achieving the maximum effect. To address this matter, a novel approach combined with the disclosed micro-container is illustrated in
[0041] In some disease prevention or treatment applications, it may require a more precise, targeted delivery to an intended site, even at the cellular level. To achieve the above stated objective, one of the key inventive aspects of this patent application is to integrate micro-containers, injectors, sensors, positioning device, motion apparatus, communications devices, and other various components with one to multiple IC devices with memory and logic processing functions on the same micro-device to achieve far greater functionality, precision, selectivity, and flexibility than those by conventional drug delivery approaches, using microelectronics processes and disclosed process flows in this application. With the aid of sensors and IC device, an injector head can precisely attach to the targeted cells and not on the un-intended cells, thereby greatly enhancing delivery selectivity, specificity and efficiency, with reduced side effects and costs over traditional approaches.
[0042] Using the novel microelectronics fabrication process flows disclosed in this application, micro-devices can be manufactured to store different types of compounds such as drugs and agents, and deliver and release the said different types of drugs and agents at desired locations, time intervals, sequence and drug doses. An array of micro-containers can be fabricated using the disclosed microelectronics processes with a desired spacing between adjacent micro-containers and container sizes, which can impact compound release dosage and density. Further, with the integration with an integrated circuit, each single micro-container, each single row of micro-containers, or any combination set of micro-containers can be selected to release stored compound. The above mentioned selective release function can also be achieved using the disclosed use of biocompatible and bio-degradable capping layer, where the thickness of bio-degradable capping layer can be varied to result in selective earlier release (using thinner bio-degradable capping layer) or selective delayed release (using thicker bio-degradable capping layer) of desired compound(s). Such a micro-device can be very powerful in releasing different types of drugs or agents at desired sequence and time interval, and combination of drugs at the targets (in-situ mixing), with effects which otherwise cannot be obtained with conventional disease treatment approaches.
[0043] One of the key novel aspects of this invention is the fabrication and resultant functions and mechanisms of micro-injectors. In one approach, a micro-container is integrated with a micro-injector housing at the bottom portion of the said micro-container. Such structures can be fabricated using novel microelectronics process flows disclosed below in
[0044] In addition to the above disclosed novel fabrication processes and process flows for making micro-containers and micro-injector mechanisms, yet another key embodiment of this application is how to fabricate integrated micro-injector and micro-container, as illustrated in
[0045] Optionally, a thin layer of space material 333 is deposited (not shown in the figure), preferably by chemical vapor deposition or atomic layer deposition, which serves to help smooth injector motion later on. Space material 333 is preferably the same material as space material 332 for ease of removal in the same etching step later on.
[0046] As shown in
[0047] As referred to above, but not illustrated in the drawings, in the case where a thin layer of space material 333 is used, it will also be removed in the same etching step, forming a spacing between movable material 223 and structural material 171, which will help the injector motion.
[0048] As another embodiment for compound injection, a micro-device with an integrated micro-injector and micro-container using a piezoelectric material as a push plate 221 below an injector base plate 222 is shown in
[0049] Another major advantage of using a micro-device with micro-containers, micro-injectors, and an integrated circuit integrated on the same unit is the ability to select the micro-container to release compound with time and space control because each micro-container can be interfaced with the integrated circuit and can be instructed by the integrated circuit on when and where to release the compound. For example, a micro-device can have an array of micro-containers, with each micro-container releasing compound based on instructions from the integrated circuit which in turn makes a decision based on a micro-sensor's measurements on a local, living environment. The micro-device can further carry multiple types of compounds stored in the array of micro-containers, with different compounds released in desired time interval and space combinations via integrated circuit instructions to achieve the optimum treatment effects. Specifically, injectors can be individually selected to launch injection action via some applied force to its base plate, triggered by instructions from an integrated circuit on the same micro-device, or by a wireless signal. As one example,
[0050] To enhance the performance and flexibility of micro-devices, in addition to micro-containers and micro-injectors, integrated circuits with data storage and logic processing capabilities and other functional components can also be integrated onto the same substrate using microelectronics fabrication techniques and process flows for biological and medical applications.
[0051] In the above integrated micro-device, the said sensors can detect a wide range of parameters and provide information to the integrated circuits for data analysis and decision making. The signal transmitters and receivers are for wireless communications with outside world (for example for a host computer outside the human body or a doctor). The said motion apparatus such as propeller can be used to position (to move) the micro-device to a desired location. Positioning device can function to determine the relative and absolute locations of the micro-device within the biological body. The integrated circuit serves as a central commander to receive data (from sensors and signal receivers), store data, analyze data, make decisions and send instructions to various components (instructing propeller for motions, injectors for compound release, transmitter for signal transmission).