The present invention relates to micro-nozzles and nano-nozzles, and methods of manufacturing micro-nozzles and nano-nozzles.
Understanding and harnessing properties of nanotechnology has and will continue to result in 21st Century breakthroughs. Products such as nano-scale computing devices, nanotechnology based fibers stronger than steel, and advanced biochemical sensors are just a few of the astounding applications of nanotechnology.
One limitation in nanotechnology is processing devices used to handle, dispense, detect, or otherwise manipulate nanoparticles. While nozzles are known for applications such as inkjet printing and other deposition processes, nano-scale nozzles are generally unknown.
Thus, there remains a need in the art for improved sub-micron and nanoscale nozzles, and efficient and reliable methods of manufacturing sub-micron and nanoscale nozzles.
The above-discussed and other problems and deficiencies of the prior art are overcome or alleviated by the several methods and apparatus of the present invention for micro and nano nozzles. A nozzle structure is provided comprising a monolithic body having an array of nozzles. The nozzles having openings with sectional openings having heights of about 100 nm or less. The nozzles are generally associated with one or more well structures.
Applications of the herein described nozzle include, but are not limited to, nanolithography, protein and DNA sequencing, and nano-chemistry, including synthesis and analysis.
The above-discussed and other features and advantages of the present invention will be appreciated and understood by those skilled in the art from the following detailed description and drawings.
Herein disclosed are nano-nozzles and methods of manufacturing nano-nozzles. With the disclosed methods, it is possible to create nozzles with opening dimensions on the order of nanometers. Further, it is possible to make such nozzles in arrays with exact spacing therebetween. Such features enable molecular level dispersion, precise material deposition, molecular level detection, and other nano-scale processes. Referring to
The present method of manufacturing nozzles may be enhanced with the use of Applicant's multi-layered manufacturing methods, as described in U.S. Non-provisional application Ser. Nos. 09/950,909, filed Sep. 12, 2001 entitled “Thin films and Production Methods Thereof”; 10/222,439, filed Aug. 15, 2002 entitled “Mems And Method Of Manufacturing Mems”; 10/017,186 filed Dec. 7, 2001 entitled “Device And Method For Handling Fragile Objects, And Manufacturing Method Thereof”; and PCT Application Serial No. PCT/US03/37304 filed Nov. 20, 2003 and entitled “Three Dimensional Device Assembly and Production Methods Thereof”; all of which are incorporated by reference herein. However, other types of semiconductor and/or thin film processing may be employed.
Referring to
The multiple layered substrate 100 includes a first device layer 110 selectively bonded to a second substrate layer 120, having strongly bonded regions 3 and weakly bonded regions 4. Using the techniques described in the above-mentioned patent applications, or other suitable wafer processing and handling techniques, the first layer 110, intended for having one or more useful structures processed therein or therein, may readily be removed from the second substrate layer 120 (which serves as mechanical support during device processing) with little or no damage to the structure(s) formed (including wells or other subtractions to the layer 110) in or on the device layer 110.
Layers 110 and 120 may be the same or different materials, and may include materials including, but not limited to, plastics (e.g., polycarbonate), insulators, semiconductor, metal conductors, monocrystalline, amorphous, noncrystalline, biological (e.g., DNA based films) or a combination comprising at least one of the foregoing various types of materials. For example, specific types of materials include silicon (e.g., monocrystalline, polycrystalline, noncrystalline, polysilicon, and derivatives such as Si3N4, SiC, SiO2), GaAs, InP, CdSe, CdTe, SiGe, GaAsP, GaN, SiC, GaAlAs, InAs, AlGaSb, InGaAs, ZnS, AlN, TiN, other group IIIA-VA materials, group IIB materials, group VIA materials, sapphire, quartz (crystal or glass), diamond, silica and/or silicate based material, or any combination comprising at least one of the foregoing materials. Of course, processing of other types of materials may benefit from the process described herein to provide multiple layer substrates 100 of desired composition. Preferred materials which are particularly suitable for the herein described methods include semiconductor material (e.g., silicon) as layer 110, and semiconductor material (e.g., silicon) as layer 120. Other combinations include, but are not limited to; semiconductor (layer 110) on glass (layer 120); semiconductor (layer 110) on silicon carbide (layer 120); semiconductor (layer 110) on sapphire (layer 120); GaN (layer 110) on sapphire (layer 120); GaN (layer 110) on glass (layer 120); GaN (layer 110) on silicon carbide (layer 120); plastic (layer 110) on plastic (layer 120), wherein layers 110 and 120 may be the same or different plastics; and plastic (layer 110) on glass (layer 120).
Layers 110 and 120 may be derived from various sources, including wafers or fluid material deposited to form films and/or substrate structures. Where the starting material is in the form of a wafer, any conventional process may be used to derive layers 110 and/or 120. For example, layer 120 may consist of a wafer, and layer 110 may comprise a portion of the same or different wafer. The portion of the wafer constituting layer 110 may be derived from mechanical thinning (e.g., mechanical grinding, cutting, polishing; chemical-mechanical polishing; polish-stop; or combinations including at least one of the foregoing), cleavage propagation, ion implantation followed by mechanical separation (e.g., cleavage propagation, normal to the plane of structure 100, parallel to the plane of structure 100, in a peeling direction, or a combination thereof), ion implantation followed by heat, light, and/or pressure induced layer splitting), chemical etching, or the like. Further, either or both layers 110 and 120 may be deposited or grown, for example by chemical vapor deposition, epitaxial growth methods, or the like.
An important benefit of the instant method and resulting multiple layer substrate 100, or thin film (e.g., layer 110) derived from the multiple layer substrate 100 is that the structures are formed in or upon the weak bond regions 3. This substantially minimizes or eliminates likelihood of damage to the useful structures when the layer 110 is removed from layer 120. The debonding step generally requires intrusion (e.g., with ion implantation), force application, or other techniques required to debond layers 110 and 120. Since, in certain embodiments, the structures are in or upon regions 3 that do not need local intrusion, force application, or other process steps that may damage, reparably or irreparable, the structures, the layer 110 may be removed, and structures derived therefrom, without subsequent processing to repair the structures. The strong bond regions 4 generally not have structures thereon, therefore these regions 4 may be subjected to intrusion or force without damage to the structures.
The layer 110 may be removed as a self supported film or a supported film. For example, handles are commonly employed for attachment to layer 110 such that layer 110 may be removed from layer 120, and remain supported by the handle. Generally, the handle may be used to subsequently place the film or a portion thereof (e.g., having one or more useful structures) on an intended substrate, another processed film, or alternatively remain on the handle.
Referring now to
In further embodiments, the wells may be formed only at the intended nozzle region, e.g., resembling grooves having the thickness shown by the dashed lines.
Referring also to
The width (i.e., the y direction as shown in
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Since the device layer including the etched well having suitable material deposited thereon is generally positioned over the weak bond region 3 of the multiple layered substrate 100, the device layer 110 may readily be removed form the support layer 120. For example, the strong bond regions 4 may be etched away by through etching (e.g., normal to the surface through the thickness of the device layer in the vicinity of the strong bond region), edge etching (parallel to the surface of the layers), ion implantation (preferably with suitable masking of the etched well and deposited material to form the nozzle, or by selective ion implantation), or other known techniques. Since the above techniques are generally performed at the strong bond regions 4 only, the etched well and material deposited in the weak bond regions 3 are easily released form the substrate, as schematically shown in
Referring now to
As shown in
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Alternatively, and referring to
In a further embodiment, and referring now to
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These etched channels 168 may then be filled with an etchable material. For example, a nozzle device 180 as describe herein, of a single layer, may be rotated approximately 90° with respect to the stack of layers having material etched away at the locations of the nozzles. An etchable material may be filled in the reservoir of the rotated nozzle structure, which is filled at the regions where the nozzles on the stack of layers are to be formed. The surrounding areas between the layers are then filled with a plug material. Then the etchable material in the nozzle region is etched away, exposing the nozzles 168′″. Using this technique, it is possible to create nozzles having approximately the same width and height (e.g., 5-10 nm by 5-10 nm). Thus, a nozzle device 10′″ having plural openings 168′″ is provided.
Note this etchable material should be selectively removable by an etchant (e.g., not removing the bulk material).
Referring now to
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Note that in any of the herein described nozzles and nozzle arrays, associated structures may be provided. For example, in certain embodiments, one or more electrodes may be provided to facilitate material discharge, detection capabilities, etc. Further, one or more processors, micro or nano fluidic devices, micro or nano electromechanical devices, or any combination including the foregoing devices may be incorporated in a nozzle device. In certain preferred embodiments, electrodes are provided at the nozzle openings and/or wells, and an electrode controller and/or a microfluidic device (e.g., to feed or remove material from the nozzles) is associated with an array of nozzles.
Referring now to
AA and BB may be the same or different materials, such as insulator or semiconductor materials to provide the structure of the nozzle 200, electrically insulate the nozzle openings from one another, fluidly seal the openings from one another, or other functionality.
In certain embodiments, the descriptive sections AL, AC, AR, NL, NR, BL, BC and BR are all of the same materials as AA and BB.
Any combination of AL, AC, AR, NL, NR, BL, BC and/or BR may be provided in the form of conductors. For example, referring back to
Further, and referring now to
A layer 238 (e.g., 5-10 nm) of conductive material is deposited on the wafer. A removable fill material 240 may be provided in the well to facilitate layering. Referring to
Referring now to
Further, one or more pairs of opposite descriptive sections may be conductive (e.g., electrodes), thereby enabling creation of fields across the nozzle opening. For example, NL and NR, AC and BC, AL and BR, AR and BL, AL, AR and BL, BR may all be electrode pairs to provide any desired functionality. Additionally, one or more conductive electrodes may be within the well regions, e.g., to provide electromotive forces to move materials.
Referring now to
For example, in certain embodiments, the sub-layers 302 are formed to very precise tolerances, e.g., having thicknesses on the order of 0.5 to about 5 nanometers. When these sub-layers 302 are formed of differing materials (e.g., alternating between insulator and semiconductor, semiconductor and conductor, or conductor and insulator), precise step motion may be enabled in the nozzle structures based on known dimensions of the nozzle sub-layers.
The herein described micro and nano nozzles may be used for various applications. For example, any known or future developed process that may employ “writing” techniques to deposit codes, conductors, patterns, devices, or any other material. These micro and nano nozzles may be used to build the soon to be ubiquitous nano-devices including electronic, mechanical, nano-fluidic, and many more.
Lithography
Any of the herein described nozzle systems may readily be employed for nanolithography. Referring now to
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Both the system of
Protein Sequencing
In certain embodiments of using the herein micro and nano nozzles, fast protein and DNA sequencing is attainable. The development of high-throughput DNA sequencers in the 90's have helped launched the genomic revolution of the 21st century. Almost on a monthly basis, one research group or another is announcing the complete sequencing of a biologically important organism. This has allowed researchers to cross reference species, finding shared and/or similar genes, and allowing the knowledge of molecular biologists in all the various fields to come together in a meaningful way. However, current techniques in DNA sequencing are far too tedious, tying up the valuable time of researchers. Even the fastest, most advanced DNA sequencers can at most process a few hundred thousand base pairs a day. The Human Genome Project took over 10 years to complete, indicating that current DNA sequencing technology still has a long way to go before it can be used as a diagnostic tool.
Using the herein nano-nozzles, a DNA sequencing method is presented that may sequence the entire Human Genome in a matter of minutes. Realizing and optimizing this technology opens new vistas for human endeavors, and enables practical applications that are nearly limitless. Culturing bacteria would be a thing of the past. Whenever faced with an unknown organism, not only could its exact species be determined immediately, but also its entire genotype, including new mutations or signs of genetic engineering. This process is based on utilization of the nanoscale nozzles and detection of ultra small and ultra fast signals. This may lead to the development of the ultimate sensor, not only for DNA, and RNA, but also to sequence denatured proteins (amino acid sequence of polypeptides).
Current DNA sequencing technology is most often based on electrophoresis and polymer chain reaction (PCR). PCR is used to create varying lengths of the DNA in question, which is then subjected to electrophoresis to resolve the size differences between the DNA fragments. However, this technique faces several bottlenecks. First, although PCR is useful in amplifying the amount of DNA material, it is time consuming, requires numerous reagents, including the use of an appropriate primer. Second, electrophoresis speed is dependent on the applied voltage. But the applied voltage cannot be further increased unless heat dissipation is similarly increased. Also, electrophoresis gel is only capable of resolving a small dynamic range (<500 bp). This requires splitting an organism's genome apart for sequencing and then re-assembling the pieces.
Instead of relying on electrophoresis to resolve the DNA sequence, the proposed sequencing technology is based on nano-electronics. Referring now to
One important factor of this method is obtaining a sufficient signal to noise ratio. The system is preferably gated and synchronized such that the ammeter will only detect a signal when a nucleotide is directly below a nozzle. The bias applied may be positive, negative, or even alternating, as to maximize the change in conductivity. Cooling may be desirable to reduce the thermal noise. Alternatively, each DNA or protein strand may be passed under several arrays of nozzles, thereby averaging out the noise.
However, if we assume a 10 picoamp current change under one applied volt, and 10 nanoseconds for detection, the signal is orders of magnitude larger than the thermal noise, even at room temperature. The sequencing speed would be enormous. Allowing 30 nanoseconds to move a nozzle from one nucleotide to the next (a speed of about 1 cm/sec), it would take only 40 nanoseconds to sequence one base pair, which is equivalent to 1.5 Billion base pairs a minute.
The above described DNA sequencing is enabled by creating a nozzle having tip dimensions on the order of about 5 Angstroms, for example, utilizing the above referenced and described nozzle manufacturing methods.
Referring now to
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The stepped motion is important in preferred embodiments, as the motion and number of steps helps maintain knowledge of position on the ssDNA, and ultimately the position of hybridization events. The stepped motion may be from about 5% to about 100% of the nozzle opening dimension, preferably about 10% to about 25% of the nozzle opening dimension.
The gating is also important in preferred embodiments, as extremely synchronized current measurements, bias, motion steps, or other excitations are crucial to ultra-fast real time DNA sequencing.
Referring now to
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As mentioned above, only a hybridization event produces a measurable (nanoseconds) current pulse at the nozzle. For proper operation, the following principles apply.
Referring now to
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To assist the denaturing in conjunction with the precise stepwise motion, the DNA strand can be straightened bay various methods. In one embodiment, electrostatic fields may be used to attract the negatively charged strands. In another embodiment, a magnetically attractive bead may be applied to an end of the DNA strand, and the strand pulled with magnetic force. In a further embodiment, viscosity optimization may be employed, such that while dragging the strand through a liquid proximate or in the channel, it will straighten upon optimal dragging velocity and fluid viscosity conditions. Further, hydrophilicity may be used, e.g., by suitable material treatment at or in the nozzles and channel walls, to attract nucleotides. In other embodiment, hydrophobicity may be used, e.g., by suitable material at or in the nozzles and channel walls, to maintain the fluid within the channel.
Thus, as shown and described, the herein system including nano-nozzles and nano-nozzle arrays are very well suited for ultra fast real time DNA sequencing operations.
Chemical Synthesis and Analysis
As is apparent to those skilled in the art of nano-chemistry or micro-chemistry, the herein described nozzles may readily be utilized in systems for combining various materials for chemical reaction, or chemical detection and analysis. For example, the nozzle may dispense a chemical “A” that interacts in a known manner with a chemical “B” provided in sufficiently close range with the nozzle. As with the above described hybridization current changes, a measurable event occurs when A interacts with B. This measurement may be, e.g., a current change, inelastic tunneling conduction, or a wavelength shift.
Further, a probe may be incorporated in the nozzle system (preferably manufactured to known dimensional relationship with the array) to measure current change, inelastic tunneling conduction, or a wavelength shift.
Additionally, DNA synthesis may be enabled by using nano-nozzle arrays of the present invention.
While preferred embodiments have been shown and described, various modifications and substitutions may be made thereto without departing from the spirit and scope of the invention. Accordingly, it is to be understood that the present invention has been described by way of illustrations and not limitation.
This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application Ser. No. 60/446,296 filed on Feb. 10, 2003, entitled “Micro-Nozzle, Nano-Nozzle, Manufacturing Methods Therefor, Applications Therefore, Including Nanolithography and Ultra Fast Real Time DNA Sequencing,” which is herein incorporated by reference.
Number | Date | Country | |
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60446296 | Feb 2003 | US |