WO2005016533A2

WO2005016533A2 - Method and apparatus for nanomotors in microfluidic devices

Info

Publication number: WO2005016533A2
Application number: PCT/US2004/026476
Authority: WO
Inventors: Yingjie Liu; Chiafu Chou; Frederic Zenhausern
Original assignee: Arizona Board Of Regents
Priority date: 2003-08-14
Filing date: 2004-08-16
Publication date: 2005-02-24
Also published as: WO2005016533A3

Abstract

A microfluidic device having one or more nanomotors which each have one or more arms or rods attached thereto where the free end of the arms or rods may be chemically altered to capture a target from a sample solution within the microfluidic device. The present invention also includes a nano-robotic assembly line contained within a microfluidic device having multiple microchannels with different sets of nanorobots for multi-step molecule synthesis or molecule/cell modification.

Description

Title: Method and Apparatus for Nanomotors in Microfluidic Devices

Field of Invention [0001] The present invention generally relates to a method and apparatus for microfluidic devices having nanorobots- More particularly, the present invention relates to a microfluidic device having nanomotors immobilized onto a surface of the device and at least one rod or arm attached to each nanomotor to facilitate the capture and transport of a target contained within a sample. The present invention also relates to the reaction of a sample containing an intended target using such microfluidic devices and the fabrication of such devices-

Background of the Invention

[0002] The intersection of nanotechnology and biology offer new tools for biotechnology applications and devices- Microfluidics involves controlling the flow of minute amounts of liquids or gases and focuses on developing more sophisticated fluid handling capabilities by designing complex systems of channels. Microfluidic devices are devices that contain these systems of channels.

[0003] The use of micropumps and micromixers are used in many microfluidic devices to enhance transport so that biomolecules can be properly detected and analyzed- Biomotors are naturally occurring proteins that exhibit certain modes of motion. For example, a unique form of rotary motion is exhibited by ATPases in response to the synthesis or hydrolysis of ATP. Such biomotors have been applied in microfluidic systems to enhance transport- [0004] However, there is a need for the formulation and utilization of microfluidic devices having nanorobots that enable cell or molecular sorting and separation by capturing and transporting targets of interest.

Summary of the Invention

[0005] The present invention is directed to the design, fabrication and use of microfluidic devices containing nanorobots. In an exemplary application, a microfluidic device includes a microchannel, at least one nanomotor immobilized within the microchannel, a first inlet for introducing a sample solution into the microchannel, a second inlet for introducing a fuel solution into the microchannel for powering the nanomotor, and a third inlet for introducing an assay solution into the microchannel- The nanomotor may have one or more arms or rods attached to it and the free end of the arms or rods may be chemically modified to capture a target contained within the sample solution-

[0006] Another exemplary embodiment of the present invention is directed to a nano-robotic assembly line contained within a microfluidic device having multiple microchannels with different sets of nanorobots for multi-step molecule synthesis or molecule/cell modification-

[0007] The present invention is also directed to a method for performing a physico-chemical reaction of a molecule sample which includes the steps of providing a physical structure capable of maintaining at least three solutions in parallel laminar flow, immobilizing a plurality of nanomotors within the physical structure where the nanomotors each include one or more arms or rods attached to them with the free end of the arms being chemically modified to capture a target, introducing a sample solution containing the target, a fuel solution to power the nanmotors, and an assay solution into the physical structure, capturing the target on the rods during movement of the rods, transporting the captures target through the fuel solution and into the assay solution during movement of the rods, and releasing and/or modifying the target in the assay solution. [0008] The present invention also includes a method for monitoring a biomolecular reaction by controlling the motion of a biological motor and/or a sub-component of the motor in a liquid phase medium from a confined environment which includes the steps of attaching one or more tags to the motor and/or sub-component, transporting one or more species in the medium which can react with the tag, screening the medium with at least an electromagnetic sensor so that a physico- chemical property change of the tag is detected by the sensor to provide detected information to produce at least one signal output representative of the interaction between the tag and species, transferring the signal output to a signal processing means responsive to differences in electromagnetic properties of the signal for generating a final output, receiving the final output into a signal processing means sufficient to generate a measurement of the information, sorting the information in accordance with the type and amount of the physico-chemical changes, and monitoring the sorted information representing a sequence of the product and/or byproduct of the interaction between the tag (attached to the motor) and the species in the medium.

Brief Description of the Drawings [0009] The present invention will be understood more fully from the detailed description given herebelow and from the accompanying drawings of the preferred embodiments of the invention. However, the drawings are not intended to imply limitation of the invention to a specific embodiment, but are for explanation and understanding only. [0010] In the drawings:

[0011] FIG. 1 is a schematic plan view of the microfluidic device having nanorobots of the present invention showing application of the invention by introducing three different solutions into the microfluidic device; [0012] FIG- 2 is the schematic plan view of FIG- 1 showing a specific microfluidic device containing ATPase nanomotors and an ATP solution for powering the robotic rods attached to the ATPase nanomotors; and [0013] FIG. 3 shows a schematic plan view of a nano-robotic assembly line inside the microfluidic device of the present invention.

Detailed Description [0014] The present invention is directed to the design, fabrication, and use of microfluidic devices containing nano-robots. Turning to FIG. 1 , the microfluidic device 10 of the present invention includes a microchannel 12, at least one nanomotor 14 immobilized in a middle of microchannel 12, and at least one arm or rod 16 attached to each nanomotor 14. MicroChannel 12 also includes three inlets or inlet channels 18, 20 and 22. First inlet channel 18 functions to introduce a sample solution A into microchannel 12, second inlet channel 20 functions to introduce a fuel solution into microchannel 12 which powers the rotation of rods 16, and third inlet channel 22 functions to introduce an assay solution C into microchannel 12. The free end of rods 16 may be chemically modified (as shown by reference number 24) in order to capture target cells or molecules of interest. [0015] MicroChannel 12 enables laminar flow, without eddies, and prevents mixing of streams flowing side by side- During use, sample solution A exhibits laminar flow in the direction of arrow X, fuel solution B exhibits laminar flow in the direction of arrow Y, and assay solution C exhibits laminar flow in the direction of arrow Z. Accordingly, there is no cross contamination between solutions which requirement is critical in some assays such as the real time monitoring of recirculating blood-

[0016] The nano-robot comprises the nanomotor and the arm or rod attached to the nanomotor and the core of the nanorobot is the nanomotor. Nanomotors can be biomotors such as the α₃β₃γ subunit of F ATPase or inorganic motors such as actuated nanomagnetic bars. MicroChannel 12 is preferably a microscale or nanoscale fluidic channel- If the nanomotor is a biomotor, one or more microscale or nanoscale arms or rods may be attached at one end to the nanomotor and their opposite, free ends can be functional ized or modified to catch target cells or molecules of interest in a sample stream flowing through the fluidic microchannel-

[0017] Fuel solution B is used to power nanomotors 14 which function to rotate rods 16. Targets of interest that are captured at the free, modified ends of rods 16 are transferred into an assay stream comprising assay solution C when rods 16 are rotated. The captured targets may then be released and/or further modified by reaction or manipulation.

[0018] The integration of nanorobots with microfluidic technology creates a new class of nanodevices with multiple applications in the fields of biomedical diagnosis, nanofabrication, photonics, optoelectronics, chemical processing such as, for example, separation, fractionation, distillation, extraction, and local switchable surface properties modifications, electronics such as, for example, transistors, field emission sources, and tunable RF antenna arrays, energy power sources such as fuel cells, new material synthesis such as, for example, Qdots, molecular assembly wires, carbon nanotubes, SiC nanowires, and nucleic acid based assemblies, and bioassay development- FIG. 2 is the schematic plan view of FIG. 1 showing a specific microfluidic device 30 containing ATPase nanomotors and an ATP solution for powering the robotic rods attached to the ATPase nanomotors. In FIG. 2, biomotors 34 comprise the α₃β₃γ subunits of F ATPase and are immobilized in the middle of microchannel 32- Microfluidic device 30 includes microchannel 32 and three inlet channels 38, 40 and 42. The nanorobot is assembled by attaching at least one microscale or nanoscale arm or rod 36 to each biomotor 34 and the free ends of rods 36 are chemically modified (as shown by reference number 44) to enable the capture of target molecules or cells of interest. Sample solution a is introduced through first channel 38, an ATP solution is introduced through second channel 40, and an assay solution b is introduced through third channel 42- Second channel 40 delivers ATP fuel solution needed to power the biomotors 34 and rods 36 rotate due to the rotation of biomotors 34 in the presence of ATP- The parallel flow of sample solution a, ATP solution, and assay solution b in relation to one another within microchannel 32 do not mix with each other due to the nature of the laminar flow within microchannel 32. The ATP fuel solution is sandwiched between sample solution a and assay solution b and flows over biomotors 34 to provide the fuel needed for motor rotation- The flow stream of ATP fuel solution also serves as a barrier to prevent sample solution a and assay solution b from coming into direct contact with one another. As previously stated above, this separation is critically important in devices monitoring blood elements in real time and in extracting and circulating biomolecules in the blood such as clotting elements and pathogens. [0020] The length of rods 36 are long enough to enable the free (chemicall modified) end of rods 36 to reach both sample solution a and assay solution by alternatively during each rotation. Preferably, the length of rods 36 are at least equal to the width of the laminar flow of the ATP solution within microchannel 32. The chemically modified free end of rods 36 capture the targets of interest present in sample solution a and carry the captured target through the ATP solution and into assay solution b for further chemical/biological reaction or modification. The captured targets may also be released into assay solution b thereby allowing the free ends of rods 36 to rotate back into sample solution a for further target capture.

[0021] Another embodiment of the present invention is illustrated in FIG. 3. FIG. 3 shows a schematic plan view of a nano-robotic assembly line inside the microfluidic device of the present invention. This embodiment shows the use of the present invention in a nano-scale molecular assembly line for multi-step molecule synthesis or molecule/cell modification. Microfluidic device 40 includes a first assay microchannel 42 containing a first set of nanorobots 43, a recirculating inlet channel 44 for introducing sample solution a, a first recirculating outlet channel 46 for introducing a solution containing a modified target into a second assay microchannel 48 containing a second set of nanorobots 49, a second recirculating outlet channel 50 for introducing a solution containing a further modified target or target containing solution into a third assay microchannel 52 containing a third set of nanorobots 53. In FIG. 3, an ATP solution is shown as the fuel solution that powers the biomotors and the ATP solution flows through first, second, and third assay microchannels 42, 48 and 52, each of which contain nano-robots which comprise biomotors. In this embodiment, targets of interest are transferred down the assembly line in separate microfluidic channels having predesigned operations depending upon the nanorobots contained within the microfluidic channels.

[0022] The embodiment shown in FIG. 3 shows that nanorobots can be used for pre-deterministic self-assembly processing which can result in a spatio-temporal controlled fabrication of small organic and/or inorganic features into preferred functional molecular devices- This spatial-temporal control increases the capability to build assemblies of mixed chemical species at specific locations on a surface, decreases the density and nature of defects, enables three dimensional assemblies, and increases the ability to build functional organic and/or inorganic devices and mixtures of such devices- This pre-deterministic self assembly with spatio-temporal controls enables the building of molecular devices comprising various electromagnetic properties such as, for example, electrical, magnetic, optical and thermal properties, and/or various chemical properties such as, for example, acidic, basic, amphiphillic, hydrophobic, and hydrophilic properties-

[0023] The present invention also includes a method for monitoring a biomolecular reaction by controlling the motion of a biological motor and/or a sub-component of the motor in a liquid phase medium from a confined environment which includes the steps of attaching one or more tags to the motor and/or sub-component, transporting one or more species in the medium which can react with the tag, screening the medium with at least an electromagnetic sensor so that a physico- chemical property change of the tag is detected by the sensor to provide detected information to produce at least one signal output representative of the interaction between the tag and species, transferring the signal output to a signal processing means responsive to differences in electromagnetic properties of the signal for generating a final output, receiving the final output into a signal processing means sufficient to generate a measurement of the information, sorting the information in accordance with the type and amount of the physico-chemical changes, and monitoring the sorted information representing a sequence of the product and/or byproduct of the interaction between the tag (attached to the motor) and the species in the medium-

[0024] In the foregoing specification, the invention has been described with reference to specific exemplary embodiments; however, it will be appreciated that various modifications and changes may be made without departing from the scope of the present invention as set forth in the claims below. The specification and figures are to be regarded in an illustrative manner, rather than a restrictive one and all such modifications are intended to be included within the scope of the present invention- Accordingly, the scope of the invention should be determined by the claims appended hereto and their legal equivalents rather than by merely the examples described above. For example, the steps recited in any method or process claims may be executed in other orders and are not limited to the specific order presented in the claims. Additionally, the components and/or elements recited in any apparatus claims may be assembled or otherwise operationally configured in a variety of permutations to produce substantially the same result as the present invention and are accordingly not limited to the specific configuration recited in the claims.

[0025] Benefits, other advantages and solutions to problems have been described above with regard to particular embodiments; however, any benefit, advantage, solution to problems or any element that may cause any particular benefit advantage or solution to occur or to become more pronounced are not to be construed as critical, required or essential features or components of any or all the claims. As used herein, the terms "comprises", "comprising", or any variation thereof, are intended to reference a non-exclusive inclusion, such that a process, method, article, composition or apparatus that comprises a list of elements does not include only those elements recited, but may also include other elements not expressly listed or inherent to such process, method, article, composition or apparatus. Other combinations and/or modifications of the above-described structures, arrangements, applications, proportions, elements, materials or components used in the practice of the present invention, in addition to those not specifically recited, may be varied or otherwise particularly adapted by those skilled in the art to specific environments, manufacturing specifications, design parameters or other operating requirements without departing from the general principles of the same.

Claims

Claims 1. A microfluidic device comprising: a channel; at least one nanomotor immobilized in a middle of the channel; a first inlet for introducing a sample solution into the channel; a second inlet for introducing a fuel solution into the channel for powering said at least one nanomotor; and a third inlet for introducing an assay solution into the channel-

2. The device of claim 1 wherein the nanomotor comprises at least one of a biomotor, an inorganic motor, a sub-component of a biomotor, and a subcomponent of an inorganic motor.

3. The device of claim 1 wherein the nanometer comprises a biological motor.

4. The device of claim 3 wherein the biological motor comprises a protein.

5. The device of claim 1 wherein said nanomotor comprises at least one of a microscale or nanoscale rod attached thereto.

6. The device of claim 5 wherein the rod is organic or inorganic.

7. The device of claim 5 wherein a free end of the rod is chemically modified to capture a target of interest contained in the sample solution.

8- The device of claim 7 wherein the rod rotates when the nanomotor is in the presence of the fuel solution.

9- The device of claim 8 wherein the solutions introduced into the channel undergo laminar flow within the channel-

10. The device of claim 9 wherein a length of the rod is at least two times a width of the laminar flow of the fuel solution-

11. The device of claim 9 wherein the sample solution, the fuel solution, and the assay solution all flow parallel to one another without mixing.

12- The device of claim 11 wherein the free end of the rod is capable of alternatively accessing the sample solution and the assay solution during each rotation.

13. The device of claim 12 wherein the nanomotor comprises a plurality of Fi- ATPase biomotors and the fuel solution comprises ATP.

14. The device of claim 13 wherein the F ATPase biomotors are immersed in the laminar flow of the ATP solution-

15- The device of claim 14 wherein the free end of the rod captures the target of interest in the sample solution and carries the target through the ATP solution and into the assay solution to undergo reaction or modification.

16- A plurality of microfluidic devices in accordance with claim 7 wherein multiple targets of interest are transferred through an assemblyline of separate channels associated with the microfluidic devices.

17. A microfluidic device comprising: an assay channel having a plurality of nanomotors immobilized therein wherein each of said nanomotors comprises at least one of a microscale or nanoscale rod attached thereto wherein a free end of each rod is chemically modified to capture a target; a first inlet channel for delivering a sample solution containing the target into the assay channel; a second inlet channel for delivering a fuel solution into the assay channel for powering the nanomotors; and a third inlet channel for delivering an assay solution into the assay channel-

18. The device of claim 17 wherein the target is altered or modified in the assay solution contained within the assay channel.

19. The device of claim 17 wherein the fuel solution is positioned between, and flows parallel to, the sample solution and the assay solution within the assay channel and all three solutions undergo laminar flow within the assay channel.

20. The device of claim 19 wherein the fuel solution powers the rotation of the rods so that the free ends of the rods can alternatively access the sample solution and the assay solution during each rotation.

21. The device of claim 17 wherein the nanomotor comprises at least one biomotor or at least one inorganic motor-

22. The device of claim 17 wherein the rod is organic or inorganic-

23- A method for performing a physico-chemical reaction of a molecule sample comprising the steps of: a) providing a physical structure capable of maintaining at least three solutions in parallel, laminar flow; b) immobilizing a plurality of nanomotors within the physical structure wherein the nanomotors each comprise a rod attached thereto where a free end of the rod is chemically modified to capture a target; c) introducing a sample solution containing the target, a fuel solution to power the rotation of the rods, and an assay solution into the physical structure; d) capturing the target on the rods during rotation of the rods; e) transporting the captured target through the fuel solution and into the assay solution during rotation of the rods; and f) releasing the target in the assay solution-

24- The method of claim 23 further comprising the step of modifying the target in the assay solution.

25. The method of claim 23 wherein the step of providing a physical structure comprises the step of providing a microchannel.

26. The method of claim 23 wherein the step of immobilizing a plurality of nanomotors within the physical structure comprises immobilizing biological motors to the physical structure and attaching a sub-micron inorganic rod to each of the biological motors.

27. The method of claim 26 wherein the step of immobilizing biological motors to the physical structure comprises the step of attaching a sub-micron metal rod to each of the biological motors.

28. The method of claim 26 wherein the step of immobilizing biological motors comprises the step of immobilizing F^ATPase protein motors to the physical structure-

29- The method of claim 28 wherein the target is an immunoglobulin.

30. The method of claim 23 wherein the step of immobilizing a plurality of nanomotors comprises the step of immobilizing a plurality of biomotors or inorganic motors-

31. The method of claim 26 wherein the step of immobilizing biological motors to the physical structure comprises the step of attaching a sub-micron organic rod to each of the biological motors.

32. The method of claim 23 wherein the step of introducing a fuel solution to power the rotation of the rods comprises the step of introducing an ATP solution-

33. The method of claim 23 wherein the step of providing a physical structure comprises the step of providing a physical structure having dimensions such that fluids flowing through the structure flow at low Reynolds numbers.

34. The method of claim 23 wherein the step of immobilizing a plurality of nanomotors comprises the step of immobilizing nanomotors and attaching a rod to each of the nanomotors that has a length equal to at least two times the laminar flow width of the fuel solution within the physical structure.

35- A method for monitoring a biomolecular reaction by controlling the motion of a biological motor and/or a sub-component of said motor in a liquid phase medium_from a confined environment comprising the steps of: attaching one or more tags to said motor and/or sub-component thereof; transporting one or more species in said medium which can react with the tag; screening the medium with at least an electromagnetic sensor so that a physico-chemical property change of said tag is detected by the sensor to provide detected information to produce at least one signal output representative of the interaction between the tag and specie; transferring the signal output to a signal processing means responsive to differences in electromagnetic properties of the signal for generating a final output; receiving the final output into a signal processing means sufficient to generate a measurement of the information; sorting the information in accordance with type and amount of the physico-chemical changes; and monitoring sorted information representative of a sequence of the product and/or by-product of the interaction between the tag attached to the motor and said one or more species in the medium.