Thin film capillary process and apparatus

Information

  • Patent Grant
  • 6649078
  • Patent Number
    6,649,078
  • Date Filed
    Wednesday, December 6, 2000
    24 years ago
  • Date Issued
    Tuesday, November 18, 2003
    21 years ago
Abstract
Method and system of forming microfluidic capillaries in a variety of substrate materials. A first layer of a material such as silicon dioxide is applied to a channel etched in substrate. A second, sacrificial layer of a material such as a polymer is deposited on the first layer. A third layer which may be of the same material as the first layer is placed on the second layer. The sacrificial layer is removed to form a smooth walled capillary in the substrate.
Description




FIELD OF THE INVENTION




The present invention relates to microfluidic substrates, and more specifically, it relates to the formation of microfluidic capillaries.




BACKGROUND OF THE INVENTION




Microfluidic technology represents a revolution in laboratory experimentation. Microfluidic circuits allow for scientific experiments that used to be performed at the laboratory bench to be done in volumes as small as a nanoliter. Microfabrication makes it possible to create intricate designs of interconnected channels that are extremely small. Each pattern is designed to produce a series of fluid manipulation steps that will execute an experiment. Hoewever, current capillary electrophoresis on a chip often requires glass to glass or quartz to quartz bonding to form the interconnected channels.




SUMMARY OF THE INVENTION




Aspects of the present invention include a method comprising: depositing a first layer on a substrate surface; depositing a second layer on the first layer; depositing a third layer on the second layer; and removing the second layer to form a capillary between the first and third layers.




Further aspects of the present invention include an apparatus comprising: a substrate having a capillary lined with a material from the group consisting of glass, quartz, polysilicon, silicon nitride, silicon dioxide, and boron nitride/silicon dioxide.











BRIEF DESCRIPTION OF THE DRAWINGS




The accompanying drawings, which are incorporated into and form a part of the disclosure,





FIGS. 1A-1I

illustrate a microfluidic device fabricated from a planar substrate.











DETAILED DESCRIPTION OF THE INVENTION




The embodiments disclosed herein are directed to improved microfluidic devices. Such devices may include a substrate having top, bottom and side surfaces and interconnected fluidic channels within which material is transported during scientific experiments such as electrophoresis. As used herein, the terms “microscale” or “microfabricated” generally refer to structural elements or features of a device which has at least one fabricated dimension in the range of from about 0.1 microns to about 500 microns. Thus, a device referred to as being microfabricated or microscale will include at least one structural element or feature having such a dimension. When used to describe a fluidic element, such as a capillary, channel, passage, or conduit, the terms “microscale,” “microfabricated” or “microfluidic” generally refer to one or more fluid capillaries, channels, passages, or conduits which have at least one internal cross-sectional dimension, e.g., depth, width, length, or diameter that is less than 500 microns, and typically between 0.1 microns and about 500 microns. A typical capillary constructed in accordance with the methods discussed below may have a width and depth in the ranges of approximately 5 to 50 microns and, typically, width and depth in the ranges of approximately 10 to 20 microns.





FIGS. 1A-1I

illustrate a method and system of using a sacrificial layer to form a capillary or channel. In a first step, shown in

FIG. 1A

, capillary images are first printed on a substrate


100


by means of standard photolithography techniques using a positive photoresist layer


102


and light


104


. Substrate


100


may be a silica based substrate from the group consisting of glass, quartz, pyrex, silicon or polysilicon, as well as other substrate materials, such as gallium arsenide. The substrate


100


may also be made of polymeric materials, (e.g., plastics such as polymethylmethacrylate (PMMA), polycarbonate, polytetrafluoroethylene (TEFLON™), polyvinylchloride (PVC), polydimethylsiloxane (PDMS), and polysulfone).




After development, the photoresist layer


102


is isotropically etched to form a channel


105


as shown in FIG.


1


B. Next, the substrate


100


is etched as shown in

FIG. 1C

to form channel


106


with a predetermined width and depth. This predetermined width may be in the range of 5 to 50 microns and, typically, 10-20 microns. The predetermined depth may also be in the range of 5 to 50 microns and, typically, 10-20 microns. In a next step, the photoresist layer


102


is removed and a first layer


108


is coated over the substrate


100


to line the channel


106


, but not fill it as shown by FIG.


1


D. The first layer


108


may be applied, for example, by electron sputtering, E-beam coating or chemical vapor deposition and may comprise one of a group consisting of glass, quartz, polysilicon, silicon nitride, silicon dioxide, boron nitride, and various metals. In the disclosed embodiment, the first layer is a silicon dioxide (SiO


2


) material with a melting temperature greater than 1000 degrees Celsius.




A second layer


110


such as a polymer having a high temperature melting point (e.g., wax) is next applied as shown in

FIG. 1E

to cover the first layer


108


through standard deposition techniques. The melting temperature of the polymer should be approximately in the range of 200 to 300 degrees Celsius, and, typically, approximately 275 degrees Celsius. This second layer


110


is a sacrificial layer or filler. In alternative embodiments, an oxide with a low temperature melting point may also be used for the second layer


110


instead of a high temperature polymer. The melting temperature of the low temperature oxide would be in the range of 200 to 250 degrees Celsius. Because of the nature of the material used in the second layer or filler


110


, there is maintained the integrity or smoothness of the first layer that may provide a capillary with a smooth walled surface. The smooth walled surface of the capillary prevents blockage or hindrance of the flow of microfluidic material as it passes through the finished capillary. Typically, the smooth walled surface in the finished capillary will have a roughness approximately in the range of 40 to 60 root mean square (rms), and, typically, approximately 50 rms.




By repeating the photolithography procedures with the same mask, but negative photoresist (not shown in figures), the filler


110


and first layer


108


is removed from the unmask surface except for the channel region. The substrate


100


is then planarized by reflowing the filler


110


in the channel


106


. A chemical mechanical polish (CMP) may then be performed to achieve a flat surface as shown in FIG.


1


F.




Next, a third layer


112


is applied to the substrate


100


which may be a similar or the same material as the first layer


108


and will, therefore, have a melting temperature greater than 1000 degrees Celsius. The third layer is deposited on top of the filler


110


so as to cover the whole surface of the substrate


100


as shown in FIG.


1


G and produce an integral mass. The third layer


112


may be applied, for example, by electron sputtering, E-beam coating or chemical vapor deposition. Since the third layer


112


is the same or similar material as the first layer


108


, the walls of the capillaries can be uniform in material. In the next step, the filler


110


is removed to form the thin film capillary


114


on the substrate


100


as shown in FIG.


1


H. The filler


110


may be removed by heating and melting process.




Optionally, the substrate


100


may be completely removed to form a stand alone, three dimensional thin film capillary as shown in FIG.


1


I.




The embodiments disclosed herein have a wide variety of uses, including, for example, capillary electrophoresis, liquid chromatograph, miniature chemical factory, polymerase chain reaction (PCR), and other microelectromechanical (MEMS) liquid fluidic gas pumping systems that requires precise injection of liquid and gas samples. Further the embodiments described herein may be used in the performance of high throughput screening assays in drug discovery, immunoassays, diagnostics, nucleic acid analysis, including genetic analysis, and the like. As such, the embodiments described herein will often include multiple sample introduction ports or reservoirs, for the parallel or serial introduction and analysis of multiple samples.




The foregoing is illustrative of the present invention and is not to be construed as limiting thereof. The invention is defined by the following claims, with equivalents of the claims to be included therein



Claims
  • 1. A method for the formation of micirofluidic capillaries, comprising:depositing a photoresist layer on a surface of a substrate, carrying out photolithography procedures to form images on the photoresist layer, etching the photoresist layer to form at least one channel therein, etching the substrate to form at least one channel therein, removing the photoresist layer, depositing a first layer over the substrate and to line the surfaces of the at least one channel formed therein, depositing a second layer over the first layer carrying out photolithography procedures on the second layer, removing the second layer and first layer from the substrate except in the at least one channel region, planarizing the substrate by reflowing the second layer material located in the channel, polishing the substrate to form a flat surface thereon, depositing a third layer on the substrate surface and over the at least one channel, removing the remaining second layer material in the at least one channel located beneath the third layer to form at least one channel in the substrate lined with said first layer material.
  • 2. The method of claim 1, additionally including removing the substrate from about the at least one lined channel.
  • 3. The method of claim 1, wherein carrying out the photolithograph procedures is carried out by forming the photoresist layer using a positive photoresist layer and a beam of light directed thereon.
  • 4. The method of claim 1, additionally providing the substrate of a material selected from the group consisting of glass, quartz, pyrex, silicon, polysilicon, gallium arsenide, and polymeric materials.
  • 5. The method of claim 1, wherein etching the photoresist layer is carried out by isotropically etching.
  • 6. The method of claim 1, wherein etching the substrate is to form the at least one channel with a width in the range of 5-50 microns and depth of 5-50 microns.
  • 7. The method of claim 1, wherein depositing the first layer is carried out using a technique selected from the group consisting of electron sputtering, E-beam coating, and chemical vapor deposition.
  • 8. The method of claim 1, wherein depositing the first layer is carried out using materials selected from the group consisting of glass, quartz, polysilicon, silicon nitride, silicon dioxide, boron nitride, and metals.
  • 9. The method of claim 8, wherein the material of the first layer is a silicon dioxide with a melting temperature greater than 1000 degrees Celsius.
  • 10. The method of claim 1, wherein depositing the second layer is carried out using a polymer having a melting point temperature in the range of 200-300 degrees Celsius.
  • 11. The method of claim 1, wherein depositing the second layer is carried out using an oxide with a melting point in the range of 200-250 degrees Celsius.
  • 12. The method of claim 1, wherein the at least one channel formed in the substrate formed so as to have a finished wall surface roughness in the range of 40-60 root mean square (rms).
  • 13. The method of claim 1, wherein carrying out the photolithography procedures on the second layer is carried out using a negative photoresist.
  • 14. The method of claim 1, wherein polishing the substrate is carried out using a chemical mechanical polish.
  • 15. The method of claim 1, wherein depositing the third layer is carried out using similar or the same material as that of the first layer and having a melting point greater than 1000 degrees Celsius.
  • 16. The method of claim 1, wherein depositing the third layer is carried out so as to cover the whole surface of the substrate and the at least one channel therein so as to produce an integral mass.
  • 17. The method of claim 1, wherein depositing the third layer is carried out by a technique selected from the group consisting of electron sputtering, E-beam coating, and chemical vapor deposition.
  • 18. The method of claim 1, wherein removing the remaining second layer material is carried out by a heating and melting process.
Government Interests

The United States Government has rights in this invention pursuant to Contract No. W-7405-ENG-48 between the United States Department of Energy and the University of California for the operation of Lawrence Livermore National Laboratory.

US Referenced Citations (55)
Number Name Date Kind
4357205 Trausch et al. Nov 1982 A
4668374 Bhagat et al. May 1987 A
4716903 Hansen et al. Jan 1988 A
4758926 Herrell et al. Jul 1988 A
4791935 Baudino et al. Dec 1988 A
4860444 Herrell et al. Aug 1989 A
4903701 Moore et al. Feb 1990 A
4935040 Goedert Jun 1990 A
4938228 Righter et al. Jul 1990 A
4997537 Karger et al. Mar 1991 A
5039492 Saaski et al. Aug 1991 A
5086772 Larnard et al. Feb 1992 A
5102415 Guenther et al. Apr 1992 A
5112460 Karger et al. May 1992 A
5113869 Nappholz et al. May 1992 A
5199428 Obel et al. Apr 1993 A
5292340 Crosby et al. Mar 1994 A
5300093 Koestner et al. Apr 1994 A
5309919 Snell et al. May 1994 A
5312446 Holschbach et al. May 1994 A
5313953 Yomtov et al. May 1994 A
5365934 Leon et al. Nov 1994 A
5383512 Jarvis Jan 1995 A
5404877 Nolan et al. Apr 1995 A
5411031 Yomtov May 1995 A
5518001 Snell May 1996 A
5533957 Aldea Jul 1996 A
5575929 Yu et al. Nov 1996 A
5583281 Yu Dec 1996 A
5628917 MacDonald et al. May 1997 A
5641400 Kaltenbach et al. Jun 1997 A
5645564 Northrup et al. Jul 1997 A
5730187 Howitz et al. Mar 1998 A
5749900 Schroeppel et al. May 1998 A
5783452 Jons et al. Jul 1998 A
5836868 Ressemann et al. Nov 1998 A
5842787 Kopf-Sill et al. Dec 1998 A
5843118 Sepetka et al. Dec 1998 A
5882936 Bensten et al. Mar 1999 A
5895398 Wensel et al. Apr 1999 A
5911737 Lee et al. Jun 1999 A
5932799 Moles Aug 1999 A
6073482 Moles Jun 2000 A
6102917 Maitland et al. Aug 2000 A
6136212 Mastrangelo et al. Oct 2000 A
6176962 Soane et al. Jan 2001 B1
6210986 Arnold et al. Apr 2001 B1
6221654 Quake et al. Apr 2001 B1
6258514 Montgomery Jul 2001 B1
6331490 Stevens et al. Dec 2001 B1
6423465 Hawker et al. Jul 2002 B1
6437551 Krulevitch et al. Aug 2002 B1
6485625 Simpson et al. Nov 2002 B1
6497995 Skrobis Dec 2002 B2
6498010 Fitzgerald et al. Dec 2002 B1
Foreign Referenced Citations (4)
Number Date Country
19638501 Apr 1998 DE
633 468 May 1994 EP
668 500 Feb 1995 EP
WO9822811 May 1998 WO