Method and device for generating a tunable array of fluid gradients

Patent metadata

Field	Value
Publication number	US-9409173-B2
Application number	US-201314092239-A
Country	US
Kind code	B2
Filing date	Nov 27, 2013
Priority date	Nov 30, 2012
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

Provided herein are devices and methods for generating microfluidic gradients, including an array of unique microfluidic gradients within an array of microchannels. Fluids within conduits are mixed in an intersection region to generate a mixed flow stream in a source reservoir channel that provides a gradient that varies with axial distance from the intersection region. Microchannels having an inlet connected to the source reservoir channel are configured to provide a microfluidic gradient in the microchannel. An outlet end of the microchannel is connected to a sink reservoir channel. By varying the ratio of fluid flow rates from the fluid conduits, the microchannel gradients are tuned. In this manner, a large number of unique gradients or array of microfluidic gradients is provided, wherein the gradient can be any number of physical or chemical parameters, including concentrations and physical fluid properties.

First claim

We claim:

1. A microfluidic gradient generator for tuning dynamic components of fluid comprising:
a first fluid conduit;
a second fluid conduit,
an intersection region that fluidically connects the first fluid conduit and the second fluid conduit, the intersection region comprising an intersection opening between the first fluid conduit and the second fluid conduit and a flow-divider that extends in a downstream direction from the intersection opening, wherein the first fluid conduit and the second fluid conduit intersect at an intersection angle relative to each other that is less than 180 degrees;
a source reservoir channel fluidically connected to the intersection region and extending downstream from the intersection opening;
a sink reservoir channel fluidically connected to the intersection region and extending downstream from the intersection opening;
a microchannel array comprising a plurality of microchannels, each microchannel having an inlet end connected to the source reservoir channel and an outlet end connected to the sink reservoir channel, wherein adjacent microchannels are separated from each other by a separation distance, wherein the microchannel array traverses an axial distance along the source reservoir channel;
wherein the first fluid conduit and the second fluid conduit are configured to provide to the intersection region a ratio of a first fluid flow rate to a second fluid flow rate to establish a mixed flow that is substantially laminar, the mixed flow comprising the first fluid and the second fluid in the source reservoir channel; a source reservoir channel gradient; and an array of microfluidic gradients that vary with the ratio of the first fluid flow rate to the second fluid flow rate;
wherein the flow-divider comprises:
an upstream sharp-edged divider that defines the downstream side of the intersection opening;
a downstream reservoir separation section that separates the source and sink reservoir channels;
an expanding central section that connects the upstream sharp-edged divider to the downstream reservoir separation section; and

wherein the microchannel array traverses the downstream reservoir separation section to fluidically connect the source and sink reservoir channels.

2. The microfluidic gradient generator of claim 1 , wherein the plurality of microchannels have an axial direction that is substantially perpendicular to an axial direction of the source reservoir channel; and the source reservoir channel and the sink reservoir channel extend along an axial direction, wherein the source reservoir axial direction and the sink reservoir axial direction are substantially parallel to each other and separated by a separation distance through which the array of microchannels traverse.

3. The microfluidic gradient generator of claim 1 , wherein:
the microchannels of the microchannel array independently have a cross-sectional area that is less than or equal to 0.1 mm 2 and a length that is greater than or equal to 0.1 mm and less than or equal to 1 cm;
the microchannels of the microchannel array independently have a volume that is greater than or equal to 1 nL and less than or equal to 1 mL;
the source and sink reservoir channels each independently have a cross-sectional area that is greater than or equal to 1 mm 2 and less than or equal to 1 cm 2 and a length that is greater than or equal to 1 mm and less than or equal to 10 cm;
the first and second fluid conduits each independently have a cross-sectional area that is greater than or equal to 1 mm 2 and less than or equal to 1 cm 2 ; and
wherein the cross-sectional areas, fluid flow-rates, fluid properties, and microfluidic gradient generator geometry are configured to provide substantially laminar flow at and downstream of the intersection region.

4. A microfluidic gradient generator for tuning dynamic components of fluid comprising:
a first fluid conduit;
a second fluid conduit,
an intersection region that fluidically connects the first fluid conduit and the second fluid conduit, the intersection region comprising an intersection opening between the first fluid conduit and the second fluid conduit and a flow-divider that extends in a downstream direction from the intersection opening, wherein the first fluid conduit and the second fluid conduit intersect at an intersection angle relative to each other that is less than 180 degrees;
a source reservoir channel fluidically connected to the intersection region and extending downstream from the intersection opening;
a sink reservoir channel fluidically connected to the intersection region and extending downstream from the intersection opening;
a microchannel array comprising a plurality of microchannels, each microchannel having an inlet end connected to the source reservoir channel and an outlet end connected to the sink reservoir channel, wherein adjacent microchannels are separated from each other by a separation distance, wherein the microchannel array traverses an axial distance along the source reservoir channel;
wherein the first fluid conduit and the second fluid conduit are configured to provide to the intersection region a ratio of a first fluid flow rate to a second fluid flow rate to establish a mixed flow that is substantially laminar, the mixed flow comprising the first fluid and the second fluid in the source reservoir channel; a source reservoir channel gradient; and an array of microfluidic gradients that vary with the ratio of the first fluid flow rate to the second fluid flow rate; and
wherein the microarray of channels are formed in a base plate and the source and sink reservoir in a top plate, and the plate and top plate are connected to form the microarray of channels positioned in a different plane from the source and the sink reservoir channels; and the base plate and the top plate are connected with an adhesive.

5. The microfluidic gradient generator of claim 1 , wherein each microchannel inlet end is positioned on a bottom surface of the source reservoir channel and each microchannel outlet end is positioned on a bottom surface of the sink reservoir channel.

6. The microfluidic gradient generator of claim 1 , wherein the first fluid conduit and sink reservoir channel form a mirror image of the second fluid conduit and source reservoir channel and the sink and source reservoir channels are interchangeable for an inverse of the ratio of the first fluid flow rate to the second fluid flow rate.

7. The microfluidic gradient generator of claim 1 , wherein the array of microfluidic gradients or a microfluidic gradient of the array has a shape that is not-linear.

8. The microfluidic gradient generator of claim 1 , wherein the array of microfluidic gradients is selected from the group consisting of:
concentration of a material suspended in the first fluid;
concentration of a material suspended in the second fluid;
ratio of the first fluid amount to the second fluid amount;
temperature;
electrical conductivity;
binding event;
amplification of template biomolecules;
concentration of a product produced by a substrate-enzyme reaction in the mixed fluid of the source reservoir channel;
concentration of a bioproduct produced from combination of a first biomolecule in the source reservoir channel and a second biomolecule in the microchannels; and
a biological event characterized by an interaction between a material suspended or formed in the mixed fluid flow and a biological cell in the microarray.

9. The microfluidic gradient generator of claim 1 , further comprising a flow-rate controller to vary the ratio of the first fluid flow rate to the second fluid flow rate, wherein the flow-rate controller provides a microfluidic gradient in a microchannel having a

Assignees

• Univ Arizona

Inventors

• Estes Matthew D
• Hurth Cedric M
• Zenhausern Frederic

Classifications

• B01L2400/0487

  fluid pressure, pneumatics · CPC title

• B01F15/0404

  Operations & Transport · mapped topic

• B01L2200/0636

  Focussing flows, e.g. to laminate flows · CPC title

• Y10T29/49826

  Assembling or joining · CPC title

• B01L2400/0472

  Diffusion · CPC title