Method and Device for Control of Diffusive Transport

Abstract
A method and apparatus are provided for regulating diffusive transport of particles between first and second portions of a channel network in a microfluidic device. The first and second portions of the channel network are in fluid communication. A first object is deposited in a first portion of the channel network and a second object is deposited in the second portion of the channel network. The diffusive transport of particles between the first and second portions of the channel network is controlled so as to allow for the study of reciprocal signaling between the objects.
Description

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings furnished herewith illustrate a preferred construction of the present invention in which the above advantages and features are clearly disclosed as well as others which will be readily understood from the following description of the illustrated embodiment.


In the drawings:



FIG. 1 is an isometric view of a microfluidic device in accordance with the present invention;



FIG. 2
a is a cross-sectional view of the microfluidic device of the present invention taken along line 2a-2a of FIG. 1;



FIG. 2
b is a cross-sectional view of the microfluidic device of the present invention taken along line 2b-2b of FIG. 1;



FIG. 3 is a schematic, cross-sectional view of the microfluidic device of the present invention taken along line 3-3 of FIG. 2a;



FIG. 4 is a cross-sectional view, similar to FIG. 3, showing an initial stage of diffusive transport between a source region and a destination region of a channel network within the microfluidic device;



FIG. 5 is a cross-sectional view, similar to FIG. 3, showing an advanced stage of diffusive transport between the source region and the destination region of the channel network within the microfluidic device;



FIG. 6 is a cross-sectional view, similar to FIG. 3, showing prevention of the diffusive transport between the source region and the destination region of the channel network with the microfluidic device in accordance the method of the present invention; and



FIG. 7 is a cross-sectional view, similar to FIG. 3, showing termination of the diffusive transport between the source region and the destination region of the channel network with the microfluidic device in accordance with the method of the present invention.





DETAILED DESCRIPTION OF THE DRAWINGS

Referring to FIG. 1, a microfluidic device for use in the method of the present invention is generally designated by the reference numeral 10. By way of example, microfluidic device 10 may be fabricated from polydimethylsiloxane (PDMS) and includes first and second ends 12 and 14, respectively, and first and second sides 16 and 18, respectively. In addition, mircofluidic device 10 includes upper and lower surfaces 20 and 22, respectively. While microfluidic device 10 has a generally rectangular configuration in the depicted embodiment, other configurations are contemplated without deviating from the scope of the present invention.


Referring to FIGS. 2a-7, microfluidic device 10 defines channel network 24 extending through the interior thereof. Channel network 24 includes central channel 26 extending along an axis. Central channel 26 has a first end 26a adjacent first end 12 of microfluidic device 10 and a second end 26b adjacent second end 14 of microfluidic device 10. First vertical portion 27 of channel network 24 projects from and communicates with first end 26a of central channel 26. First vertical portion 27 terminates at input port 28 that communicates with upper surface 20 of microfluidic device 10, FIG. 1. Second vertical portion 30 of channel network 24 projects from and communicates with second end 26b of central channel 26. Second vertical portion 30 terminates at output port 32 that also communicates with upper surface 20 of microfluidic device 10, FIG. 1. As best seen in FIGS. 3-7, central channel 26 has a reduced diameter portion 37 adjacent first end 26a thereof, for reasons hereinafter described.


Referring to FIGS. 2b-7, channel network 24 further includes source region 34 and destination region 36. Source region 34 includes a horizontal source channel 35 having a first end 35a adjacent first side 16 of microfluidic device 10 and a second end 35b communicating with central channel 26. First vertical source portion 38 of source region 34 projects from and communicates with first end 35a of source channel 35. First vertical source portion 38 terminates at input port 40 that communicates with upper surface 20 of microfluidic device 10, FIGS. 1 and 2b. Destination region 36 includes a horizontal destination channel 44 having a first end 44a adjacent second side 18 of microfluidic device 10 and a second end 44b communicating with central channel 26. Destination channel 44 is axially aligned with source channel 35 and communicates with source channel 35 though communication portion 46 of central channel 26. First vertical destination portion 48 of destination region 36 projects from and communicates with first end 44a of destination channel 44. First vertical destination portion 48 terminates at input port 50 that communicates with upper surface 20 of microfluidic device 10, FIGS. 1 and 2b.


In operation, channel network 24 is filled with a fluid. Thereafter, a user-desired object such as a cell, molecule or the like 49 is introduced into source region 34 though input port 40. Similarly, a user-desired object such as a cell, molecule or the like 51 is introduced into destination region 36 though input port 50. As best seen in FIG. 4, the object in source region 34 of channel network 24 may act as a source of diffusing molecules. Over time, the molecules diffused by the object in source region 34 of channel network 24 enter the destination region 36 through communication portion 46 of central channel 26 and communicate with the object therein, FIG. 5. As a result, signaling between the object in the source region 34 and the object in destination region 36 may be observed for study.


In order to terminate the object to object communication, a large reservoir drop 52 is deposited by a micropipette of robotic micropipetting station over output port 32 of channel network 24, FIG. 2. The radius of reservoir drop 52 is greater than the radius of output port 32 and is of sufficient dimension that the pressure at output port 32 of channel network 24 is essentially zero. A pumping drop 54, of significantly smaller dimension than reservoir drop 52, is deposited on input port 28 of channel network 24. Pumping drop 54 may be hemispherical in shape or may be other shapes. As such, it is contemplated that the shape and the volume of pumping drop 54 be defined by the hydrophobic/hydrophilic patterning of the surface surrounding input port 28 in order to extend the pumping time of the method of the present invention. As heretofore described, microfluidic device 10 is formed from PDMS which has a high hydrophobicity and has a tendency to maintain the hemispherical shapes of pumping drop 54 and reservoir drop 52 on input and output ports 28 and 32, respectively. It is contemplated as being within the scope of the present invention that the fluid in channel network 24, pumping drops 54 and reservoir drop 52 be the same liquid or different liquids.


Because pumping drop 54 has a smaller radius than reservoir drop 52, a larger pressure exists on the input port 28 of channel network. The resulting pressure gradient causes the pumping drop 54 to flow from input port 28 through channel network 24 towards reservoir drop 52 over output port 32 of channel network 24. It can be understood that by sequentially depositing additional pumping drops 54 on input port 28 of channel network 24 by the micropipette of the robotic micropipetting station, the resulting pressure gradient will cause the pumping drops 54 deposited on input port 28 to flow through channel network 24 towards reservoir drop 52 over output port 32 of channel network 24. As a result, fluid flows through central channel 26 of channel network 24 from input port 28 to output port 32. A constriction such as reduced diameter portion 37 of central channel 26 of channel network 24 is provided upstream of communication portion 46 in order to reduce the flow rate of the fluid flowing through central channel 26 of channel network 24 from input port 28 to output port 32.


It can be appreciated that given sufficient fluid flow through central channel 26 of channel network 24, the diffusive transport of molecules from source region 34 into communication portion 46, and hence, into destination region 36 may be terminated, FIG. 6. Alternatively, by reducing the flow rate of the fluid flow through central channel 26 of channel network 24, the fluid flowing through central channel 26 of channel network 24 may be used to capture the molecules diffusing into communication portion 46 and carry such molecules to output port 32 of channel network 24, FIG. 7. Further, it can be appreciated that by slowing the flow rate of the fluid flowing through central channel 26 of channel network 24, molecules of a predetermined size may be able to pass through the fluid flowing through communication portion 46 of channel network 24 into destination region 36.


The flow rate of the fluid flowing through central channel 26 of channel network 24 may be varied by changing the dimensions of central channel 26 and/or the dimensions of reduced diameter portion 37 of central channel 26. Alternatively, the flow rate of the fluid flowing through central channel 26 of channel network 24 may be varied by changing the volume of reservoir drop 52 and/or the volume of pumping drop 54.


Various modes of carrying out the invention are contemplated as being within the scope of the following claims particularly pointing out and distinctly claiming the subject matter, which is regarded as the invention.

Claims
  • 1. A method of controlling diffusive transport between first and second portions of a channel network in a microfluidic device, the first and second portions of the channel network being in fluid communication, comprising the steps: providing a flow path in the microfluidic device, the flow path having an input and an output and extending between the first and second portions of the channel network; andflowing a predetermined fluid along the flow path at a flow rate so as to selectively control diffusive transport of particle between the first and second portions of the channel network.
  • 2. The method of claim 1 wherein the step of flowing the predetermined fluid includes the additional step of increasing the flow rate of the predetermined fluid to predetermined level to isolate the first portion of the channel network from the second portion of the channel network and prevent diffusive transport of particles therebetween.
  • 3. The method of claim 1 further comprising the additional step of placing a constriction in the flow path to reduce the flow rate of the predetermined fluid flowing therethrough.
  • 4. The method of claim 3 wherein: the first and second portions of the channel network are in fluid communication through a junction;the junction intersects the flow path; andthe constriction is upstream of the junction.
  • 5. The method of claim 1 further comprising the additional step of stopping the flow of the predetermined fluid to allow diffusive transport of particles between the first and second portions of the channel network.
  • 6. The method of claim 1 further comprising the additional step of reducing the flow rate of the predetermined fluid to allow particles of a predetermined minimum size to diffuse between the first and second portions of the channel network.
  • 7. The method of claim 1 comprising the additional steps of: depositing a first object in the first portion of the channel network; anddepositing a second object in the second portion of the channel network.
  • 8. A method of regulating diffusive transport of particles between first and second portions of a channel network in a microfluidic device, the first and second portions of the channel network being in fluid communication, comprising the steps: depositing a first object in a first portion of the channel network;depositing a second object in the second portion of the channel network; andselectively controlling diffusive transport of particles between the first and second portions of the channel network.
  • 9. The method of claim 8 comprising the additional step of providing a flow path in the microfluidic device, the flow path having an input and an output and extending between the first and second portions of the channel network.
  • 10. The method of claim 9 wherein the step of controlling diffusive transport includes the step of flowing a predetermined fluid along the flow path at a flow rate so as to isolate the first portion of the channel network from the second portion of the channel network and prevent the diffusive transport therebetween.
  • 11. The method of claim 9 wherein the step of controlling diffusive transport includes the step of flowing a predetermined fluid along the flow path at a predetermined flow rate so as to allow particles of a predetermined minimum size to diffusive between the first and second portions of the channel network.
  • 12. The method of claim 9 further comprising the additional step of placing a constriction in the flow path.
  • 13. The method of claim 12 wherein: the first and second portions of the channel network are in fluid communication through a junction;the junction intersects the flow path; andthe constriction is upstream of the junction.
  • 14. The method of claim 9 wherein the step of selectively controlling diffusive transport of particles includes the step of flowing a predetermined fluid along the flow path.
  • 15. The method of claim 14 further comprising the additional step of stopping the flow of the predetermined fluid to allow diffusive transport of particles between the first and second portions of the channel network.
  • 16. A microfluidic device, comprising: a body defining an input, an output, a channel network having first and second portions communicating with each other through a junction and a flow path extending from the input to the output through the junction; anda flow constriction in the flow path upstream of the junction.
  • 17. The microfluidic device of claim 16 further comprising a first introduction port communicating with the first portion of the channel network.
  • 18. The microfluidic device of claim 17 further comprising a second introduction port communicating with the second portion of the channel network.
  • 19. The microfluidic device of claim 16 wherein the first portion of the channel network is in fluid communication with the second portion of the channel network.
  • 20. The microfluidic device of claim 16 further comprising a first biological object disposed in the first portion of the channel network, a second biological object disposed in the second portion of the channel network, and fluid selectively flowing along the flow path at a flow rate, the fluid controlling diffusion between the first and second biological objects.