Patent Document

FIELD OF INVENTION  
         [0001]    The invention relates to microfluidic devices. In particular the invention relates to a method for integrating microfluidic channels onto a substrate including a microelectronic structure such as a source of light or a light detector.  
         BACKGROUND OF THE INVENTION  
         [0002]    Integrated microsystems have a number of important applications, especially in the field of biological material analysis. Such systems typically direct a light source at a sample and detect the light reflected from, transmitted through, or fluorescing from the sample.  
           [0003]    One problem impeding wide adaptation of such integrated microsystems is the cost and complexity of such systems. In order to minimize cross contamination between biological samples, microchannels carrying the biological samples are typically designed to be disposable. Thus each microsystem needs to be inexpensive and simple to fabricate.  
           [0004]    Microfluidic devices are generally made by subtractive processes, such as etching features into a glass or silicon substrate (“Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip” Harrison, D. J.; Fluri, K.; Seiler, K.; Fan, Z.; Effenhauser, C. S.; Manz, A.; Science 1993 261 895-897), or by a molding procedure, typically using a polymeric material (“Integrated Capillary Electrophoresis on Flexible Silicone Microdevices: Analysis of DNA Restriction Fragments and Detection of Single DNA Molecules on Microchips” Effenhauser, C. S.; Bruin, G. J. M.; Paulus, A.; Ehrat, M.;  Anal. Chem.  1997; 69(17); 3451-3457). As will be explained, these processes impart limitations on the fabrication of totally integrated devices.  
           [0005]    Both microfluidic channels and electronic elements can be fabricated using conventional processing on silicon substrates (“An Integrated Nanoliter DNA Analysis Device” M. A. Bums, B. N. Johnson, S. N. Brahmasandra, K. Handique, J. R. Webster, M. Krishnan, T. S. Sammarco, P. M. Man, D. Jones, D. Heldsinger, C. H. Mastrangelo, and D. T. Burke;  Science  Oct. 16, 1998; 282: 484-487). Typically, the same substrate material is used to form the passive fluidic channels and to serve as the growth substrate upon which the active electronic devices are grown. However, such techniques result in a low density of active devices being processed on each growth substrate because the passive channels typically cover a large area relative to the electronic devices. The high cost of silicon processing associated with active device formation and the low density of active devices on the growth substrate makes this process expensive. In addition, it may be difficult to add components from other solid-state materials such as III-V semiconductors.  
           [0006]    Molding procedures are sometimes used to fabricate passive microfluidic channel structures. While molding can be done with relatively high precision, it is difficult to integrate active electronic devices with good registration between the channels and electronic devices using conventional molding processes (“An Integrated Fluorescence Detection System in Poly(dimethylsiloxane) for Microfluidic Applications” M. L. Chabinyc, D. T. Chiu, J. C. McDonald, A. D. Stroock, J. F. Christian, A. M. Karger, G. M. Whitesides, and “Fluidics Cube for Biosensor Miniaturization”; J. M. Dodson, M. J. Feldstein, D. M. Leatzow, L. K. Flack, J. P. Golden, and F. S. Ligler  Anal. Chem.,  73 (15), 3776-3780, 2001).  
           [0007]    Another difficulty with current fabrication techniques is that combining dissimilar elements by direct growth and micromachining on the same substrate to form a single integrated unit has proven to be technically difficult. For example, the microchannels, the semiconductor light emitters and detectors are formed from materials that are incompatible such that fabrication together in a single process results in poor quality devices. This incompatibility stems partly from the fact that thermal processing stability and thermal management techniques used in the fabrication of most high efficiency optoelectronic light sources are incompatible with the formation of plastic or glass structures that are typically used to form a microchannel.  
           [0008]    Thus an improved method of fabricating a microsystem that integrates a micro-fluidic channel aligned with other electronic or opto-electronic component onto a single platform at a reduced cost and complexity is desired.  
         SUMMARY OF THE INVENTION  
         [0009]    A method for integrating an electronic device structure and microchannel onto a substrate is described. The method includes forming a structure such that the structure is fixed to a substrate. Channel features are fabricated on the substrate aligned in close proximity to the structure. A mold is formed over the channel features. Finally the channel features are removed to create a channel that transports a fluidic sample being tested. The channel is positioned such that structure interacts with the channel.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]    [0010]FIG. 1 shows one embodiment of a simple microchannel device with integrated thin film filters and photo detectors.  
         [0011]    [0011]FIG. 2 shows a waveguide implemented in an integrated microstructure.  
         [0012]    [0012]FIG. 3 is a table listing possible mold materials used to fabricate the channel walls and their respective indexes of refraction.  
         [0013]    [0013]FIG. 4 shows an integrated light source and microchannel including a lens integrated into a microchannel wall.  
         [0014]    [0014]FIG. 5 shows an integrated light source and microchannel including a waveguide that divides light from the light source.  
         [0015]    FIGS.  6 - 9  shows the process of forming a light source and integrating it onto a substrate.  
         [0016]    FIGS.  10 - 11  shows the process of forming a channel through a mold  
         [0017]    [0017]FIG. 12 shows an alternative process of forming a channel through a mold.  
         [0018]    FIGS.  13 - 15  show the process of attaching a filter and detector to the integrated light source and microchannel structure.  
         [0019]    [0019]FIG. 16 shows an example MEMs structure suitable for integration with a plurality of microfluidic channels. 
     
    
     DETAILED DESCRIPTION  
       [0020]    A method and structure for integrating optoelectronic components with microfluidic devices is provided. FIG. 1 illustrates a typical integrated structure that may be formed. In FIG. 1, a light source  104  such as a laser diode is bonded to a substrate  108 . A housing material  112 , typically epoxy or a polymer such as poly(dimethylsiloxane) PDMS, bonded to the same substrate  108  forms a microchannel  116  that carries a sample to be tested.  
         [0021]    Light  120  emitted by light source  104  propagates through housing material  112  and is incident upon the sample  124  being tested. Sample  124  scatters incident light, both reflecting, refracting, or fluorescing light through filter  124  to a detector  128 , such as a silicon photodetector. Information about the sample can be obtained by measuring the frequency, intensity and other parameters of the detected light.  
         [0022]    In order to further guide the light emitted by light source  104  a waveguide may be integrated into the housing material  112 . The waveguide guides the light from light source  104  to the channel or a plurality of channels. FIG. 2 shows a waveguide  204  integrated into second housing material  208 . FIG. 3 shows a table that lists possible materials used to fabricate second housing material  208  and waveguide  204 . PDMS is a convenient housing material due to its compatibility with plastic substrates and its minimal autofluorescence characteristics. Minimal autofluorsecence is important in fluorescent detection systems. Epoxies have the advantage of being compatible with thin-film layer lift-off and transfer techniques and being relatively non-reactive to biological materials. By integrating other materials listed in table  3  with PDMS or epoxy, the index of refraction can be controlled to form waveguide  204  through the housing material. Integration of the waveguide into housing material  208  allows more efficient collection and concentration of light from light source  212 . The structure shown in FIG. 2 includes two channels  216 ,  220  enabling the testing of two samples  224 ,  228 .  
         [0023]    The technology that enables integrating waveguides into the housing also allows lenses to be formed to concentrate light from the light source. FIG. 4 shows a lens  404  coupled to the termination of waveguide  408 . Lens  404  focuses light into channel  412 . Using a lens  404  to focus light into a smaller spot size substantially improves the spatial resolution of a biodetection chip formed from the structure of FIG. 4.  
         [0024]    Alternately, a waveguide can divide the output of a light source into two different light paths. FIG. 5 shows a waveguide  504  that divides light from a light source  508  into two components enabling monitoring of a sample flowing along channel  512 . By measuring the time delay between closely spaced events, the flow speed, and/or spatial distribution of the biomolecules in solution can be detected. For example, when an opaque object reaches a first beam  516 , the object causes a drop in reflected light intensity at a first time, to. When the same object reaches a second beam  520 , the object causes a second drop in reflected light intensity at time t 0 +(change in time). The flow speed is then determined by dividing the distance  524  between first beam  516  and second beam  520  by the (change in time).  
         [0025]    FIGS.  6 - 14  describe several methods of fabricating the structures shown in FIGS.  1 - 5 . FIGS.  6 - 14  show a process flow that describes fabrication of an integrated optoelectronic system including a microfluidic channel. Although FIGS. 2, 4 and  5  show various embodiments of a microfluidic channel structure using waveguides and optics, the procedures shown in FIGS.  6 - 14  will describe general fabrication of a light source and a microchannel. The procedure may be easily modified to add waveguides and lenses by adjusting the index of refraction of the molding material during fabrication. In alternate embodiments, the light source is positioned close enough to the microchannel and the sample being tested that waveguides and lenses to direct the light are unnecessary.  
         [0026]    [0026]FIG. 6 illustrates a light emitting device or light source  604  such as a GaN based laser diode or other edge-emitting laser fabricated on a growth substrate  608 . The growth substrate is material is typically selected to lattice match to the laser diode. Sapphire is one example of a material that provides a good lattice match to a GaN based laser diode.  
         [0027]    In FIG. 7, the light source  604  is flip-chip bonded to an integrated device substrate  704 . The gap between light source  604  and device substrate  704  may be filled with a bonding material  708  such as epoxy. Bonding material  708  fills the gap and creates a robust bond between device substrate  704  and light source  604 .  
         [0028]    The illustrated embodiment describes flip-chip bonding, although such a design is not required. In alternate embodiments, the growth substrate serves also serves as the integrated device substrate. Thus the micro-fluidic channels are fabricated directly on the growth substrate eliminating the need for flip chip bonding. However, such a structure would be more expensive. The expense of the optical source fabrication procedure in addition to the high cost of most growth substrates, such as sapphire, makes such designs less appealing. Thus a flip chip design that allows a high density of optical devices to be formed on each growth substrate and flip chip bonds each individual optical source device to a relatively inexpensive device substrate  704  is less costly.  
         [0029]    In FIG. 8, the growth substrate  608  is removed. One common method of removing growth substrate  608  uses a laser lift off process as described in U.S. patent application Ser. No. 09/648,187 entitled “Structure and Method for Separation and Transfer of Semiconductor Thin Films Onto Dissimilar Substrate Materials” filed Aug. 23, 2000 and hereby incorporated by reference. Although removal of growth substrate  608  is not required, when high heat producing light sources are used, removal of growth substrate  608  combined with the use of the flip-chip mounting provides an exposed light source surface which is convenient for mounting a heat sink.  
         [0030]    In FIG. 9, a heat sink  904  is bonded to the light source  604 . When light source  604  is a semiconductor laser, especially a continuous-wave operation laser that utilizes relatively high current densities or a GaN-based blue laser, substantial heat is generated during operation. Heating of the microsystem is undesirable considering the close proximity of laser to the microchannel. Given the close proximity, excessive heating can distort the microchannel and/or substrate structure thereby degrading alignment of the light source with the microfluidic channel and detector. Excessive heat could also damage sensitive biological samples flowing through the microchannel. To avoid such damage, heat sink  904  dissipates thermal energy generated by light source  604 .  
         [0031]    One method of attaching a heat sink involves depositing a high thermal conductivity metal  908  onto the backside of exposed light source  604 . The deposition may be accomplished using a variety of techniques such as spin coating, sputtering or other deposition techniques that are well known in the art. Heat sink  904  is subsequently attached or bonded to the high thermal conductivity metal.  
         [0032]    In FIG. 10, a series of channel features  1004 ,  1008 ,  1012  are printed onto device substrate  704 . Each channel feature will define a microchannel for carrying a sample material being tested. One method of forming the channel features is to use wax ink jet printing as described in U.S. patent application Ser. No. 09/838,684 entitled “Method for Printing Etch Masks Using Phase-Change Materials” filed Apr. 19, 2001 and which is hereby incorporated by reference. The channel features are usually aligned to transferred light source  604 .  
         [0033]    The alignment of features to the light source  604  or other opto-electronic device may be done using a variety of techniques. One method of achieving such alignment utilizes a sensor, such as a camera, and a feedback control system. The sensor or camera determines the position of light source  604  with respect to where a deposition mechanism, such as a piezo-electric printhead to deposit features  1004 , is positioned. The feedback control system receives information from the sensor and repositions the deposition mechanism until an ideal position is achieved. The ideal position is defined to be when the deposition mechanism is positioned to form features that are aligned to light source  604 . Additional details of such a control system are described in U.S. patent application Ser. No. 10/224,701 entitled “Method For The Printing Of Homogeneous Electronic Material With A Multi-Ejector Print Head” which is hereby incorporated by reference.  
         [0034]    The proximity of each channel feature  1004  to adjacent channel features  1008 , and the dimensions of the channel features are determined by the resolution of the printing system. Using special printing systems, especially printing systems that use piezo-electric drivers to generate ejection of micro-droplets as described in U.S. patent application Ser. No. 10/224,701 entitled “Method for the Printing of Homogeneous Electronic Material With a Multi-Ejector Print Head” filed Aug. 20, 2002, and hereby incorporated by reference and adjusting the temperature of the ejected droplet and the device substrate surface to control spreading of the droplet as described in the previously cited reference U.S. application Ser. No. 09/838,684 entitled “Method for Printing Etch Masks Using Phase-Change Materials”, very small channel features may be fabricated. Using such special print systems, the typical spacing between adjacent channels features typically ranges between 100 and 300 micrometers with each channel feature having a cross sectional width of less than 100 micrometers.  
         [0035]    In order to fabricate micro-channels, material that forms the walls of the microfluidic channel are deposited over channel features  1004 ,  1008 ,  1012 . In FIG. 11, a deposited prepolymer mold  1104  material encapsulates channel features  1004 ,  1008 ,  1012 . The prepolymer mold also may or may not enclose light source  604 . However, enclosing light source  604  avoids transmitting light source output through a prepolymer mold—air interface thereby avoiding light losses associated through such a transmission. In an alternate embodiment, materials with different indexes of refraction may be deposited in layers to form a waveguide in prepolymer mold  1104 . Such waveguide structures were illustrated in FIGS. 2, 4 and  5 .  
         [0036]    After forming the mold, channel features  1004 ,  1008 ,  1012  are removed to create a channel for carrying a fluid sample. Four techniques will be described to remove the wax or create the channel structure, although other techniques may be used.  
         [0037]    A first method of creating the channel structure involves waiting until prepolymer mold  1104  is cured and then dipping the channel features and mold  1104  in a solvent. The solvent dissolves the channel features leaving an open channel to transport a fluidic sample. When the channel features are a printed wax, such as Kemamide-based wax sold by Crompton Corporation of Taft, La., a suitable solvent is tetrahydrofuran or other organic solvent.  
         [0038]    A second method of creating the channel structure forms prepolymer mold from a pol(dimethylsiloxane) (PDMS) material or similar material. As illustrated in FIG. 12, the PDMS mold  1204  can be cured and than peeled away from the device substrate  1208 . The material used to form mold  1204  should therefore be capable of being separated from the device substrate while retaining structural integrity. After removal of PDMS mold  1204 , a solvent or other stripping technique such as planarization, is used to remove channel features  1004 ,  1008 ,  1012 .  
         [0039]    After the channel features are removed, the PDMS channel mode  1204  is returned to the original position in which it was formed and reattached to device substrate  1208 . The original position properly aligns the channels to the light source. The described method of removing and reattaching the mold reduces the time in which the circuit is immersed in a solvent compared to immersing the channel features in a solvent without first removing the mold. It also enables the use of other channel feature removal techniques such as planarization. However, the process of removing and reattaching the mold introduces the additional steps of realigning the PDMS channel mold  1204  with the light source and reattaching the mold  
         [0040]    A third method of forming the channels is through a backside exposure similar to that described in U.S. patent application Ser. No. 10/303,551 entitled “Method of Fabrication of Electronic Devices Using Microfluidic Channels” filed Nov. 22, 2002 and hereby incorporated by reference. This third method utilizes a transparent device substrate  704 . A thin opaque film is deposited over device substrate  704 . The opaque film is an etch mask used to define a pattern of micro-channels. A photosensitive polymer such as SU-8 is deposited over the patterned opaque film. Radiation transmitted through transparent device substrate  704  cures exposed regions of the photosensitive polymer in a backside exposure process. Uncured regions of the photosensitive polymer are removed, typically using a solvent such as toluene, leaving a pattern of micro channels through the cured photosensitive polymer. A cap structure formed from PDMS is placed over the channels to form capped micro-channels through which flows fluidic samples to undergo testing.  
         [0041]    After formation of the micro-channels using any of the above described techniques, or other techniques available to those of ordinary skill in the art, a system to detect the interaction of incident light on samples flowing in the channel may be implemented. One such method is to integrate a light filter and detector above where the micro-channels have been formed. FIGS.  13 - 15  show one method of forming such a light filter and detector structure.  
         [0042]    In FIG. 13, a filter  1304  is grown on a filter growth substrate  1308 . Filter  1304  is bonded or otherwise attached to mold  1104 . An epoxy or another adhesive may be used to bond filter  1304  to mold  1104 . An appropriate filter for detecting light scattered by samples in the channel should be tuned to the frequency output of the light source. When light source  604  is an InGaN based laser that was formed on a sapphire growth substrate, an appropriate filter is a thin film of InGaN also grown on a sapphire growth substrate. The InGaN thin film layer is tuned to the output frequency of the InGaN based laser diode.  
         [0043]    In FIG. 14, the growth substrate  1308  is removed. Removal of growth substrate  1308  may be done using a variety of techniques, including, but not limited to, laser lift-off as described in the previously cited reference U.S. patent application Ser. No. 09/648,187 entitled “Structure and Method for Spearation and Transfer of Semiconductor Thin Films Onto Dissimilar Substrate Materials”, planarization of the surface or various etching techniques. After removal, of growth substrate  1308 , a detector may be attached to filter  1304 . FIG. 15 shows a detector  1504  attached onto filter  1304 . The detector is typically a semiconductor photodetector that is sensitive to the frequency of light scattered by reflected or refracted light from the sample. Filter  1304  prevents “noise” from other light sources from reaching detector  1504 .  
         [0044]    Although the illustrated structure is suitable for many applications, one particular use for the integrated opto-electronic micro-fluidic channel structure is to perform bio-analytic testing. GaN based light emitting diodes typically emit at a wavelength between 390-530 nm which is compatible with most fluorescent dyes used in biological analysis. When collimated light sources are needed, laser diodes may be substituted for the light emitting diodes. Waveguides and lenses may be used to further focus and detect the light.  
         [0045]    Shorter wavelength GaN based LEDs and laser diode devices targeting wavelength ranges between 260 nm and 350 nm are under development. When such devices become available, they may be combined with the integration techniques described herein to enable direct fluorescence excitation of DNA or proteins.  
         [0046]    Longer wavelength light sources are also applicable to bio-analytical systems. The light-source used in conjunction with specific dyes sensitive to wavelengths in the red and infrared regime can also be used for dye fluorescence excitation. Solid-state optoelectronic devices such as laser diodes and light emitting diodes based on the arsinide and phosphide materials system are readily available to provide the incident excitation source for the integrated bio-analytical system.  
         [0047]    The interaction between electronic device structure and the fluid in the microchannel is not limited to optical excitation from a light source. The device aligned to the microchannel may also be a microelectromechanical system (MEMS) device used to pump, divert, or mix fluids within the microchannel. In one embodiment of the invention, a microchannel is aligned and positioned to a MEMS device to direct the fluid into the MEMS structure. For example, FIG. 16 shows one example of a MEMs structure or integrated device  1610  designed to pump and mix two fluids. In FIG. 16, a diverter  1650  combines two fluids, a first fluid  1660  in one channel  1630  and a second fluid  1670  from second channel  1640 . The combined fluids  1680  flows into a third microchannel  1635  for delivery to separate area  1650  through micropump  1600 .  
         [0048]    The preceding description and illustrations provide many details and instructions on building and using an integrated optoelectronic device. These details are provided to facilitate understanding of the device and should not be interpreted to limit the scope of the invention. For example, many of the procedures describe using the integrated structure to test for a sample, usually a biological sample flowing in a microchannel. However, the integrated structure described has many other applications such as testing for explosives or to analyze inorganic samples. The preceding specification also provides detailed instructions on how to fabricate the integrated structure. For example, printing technology and materials used have been described. However, these techniques and materials as well as other process details may be altered and still fall within the scope of the invention. Thus, the invention should not be limited by the preceding specification but only by the claims which follow.

Technology Category: 5