WikiPatents - Community Patent Review
Create Free Account  |  License or Sell Your Patent  |  WikiPatents Marketplace  |  WikiPatents Blog
Username:  Password:  
    
Advanced Search
Microfluidic systems incorporating varied channel dimensions    
United States Patent5842787   
Link to this pagehttp://www.wikipatents.com/5842787.html
Inventor(s)Kopf-Sill; Anne R. (Portola Valley, CA); Parce; John Wallace (Palo Alto, CA)
AbstractThe present invention is generally directed to improved microfluidic devices, systems and methods of using same, which incorporate channel profiles that impart significant benefits over previously described systems. In particular, the presently described devices and systems employ channels having, at least in part, depths that are varied over those which have been previously described. These varied channel depths provide numerous beneficial and unexpected results.



 Title Information Submit all comments and votes
 
Patent Text Patent PDF Print Page Summary File History
Plain text PDF images Print Summary File History
Inventor     Kopf-Sill; Anne R. (Portola Valley, CA); Parce; John Wallace (Palo Alto, CA)
Owner/Assignee     Caliper Technologies Corporation (Palo Alto, CA)
Patent assignment
All assignments
Publication Date     December 1, 1998
Application Number     08/948,194
PAIR File History     Application Data   Transaction History
Image File Wrapper   Patent Term   Fees
Litigation
Filing Date     October 9, 1997
US Classification    
Int'l Classification    
Examiner     Soohoo; Tony G.
Assistant Examiner    
Attorney/Law Firm     Murphy; Matthew B.
Address
Parent Case    
Priority Data    
USPTO Field of Search    
Patent Tags     microfluidic incorporating varied channel dimensions
   
Enter a comma (,) or semicolon (;) between multiple tag words/phrases.
Describe this patent:
 Amusing   
 Clever   
 Complex   
 Efficient   
 Historic   
 Important   
 Innovative   
 Interesting   
 Practical   
 Simple   
[no votes]
Patent WIKI

Share information and news about this patent, including information and news about the technology, inventors, company, ligation and licensing.

 References Submit all comments and votes
 
*references marked with an asterisk below are user-added references
 U.S. References
 
Add a new US reference:  
ReferenceRelevancyCommentsReferenceRelevancyComments
5744366
Kricka
436/63
Apr,1998

[0 after 0 votes]
5637469
Wilding
435/7.21
Jun,1997

[0 after 0 votes]
5635358
Wilding
435/7.2
Jun,1997

[0 after 0 votes]
5603351
Cherukuri
137/597
Feb,1997

[0 after 0 votes]
5593838
Zanzucchi
435/6
Jan,1997

[0 after 0 votes]
5585069
Zanzucchi

Dec,1996

[0 after 0 votes]
5571410
Swedberg
210/198.2
Nov,1996

[0 after 0 votes]
5500071
Kaltenbach
156/272.8
Mar,1996

[0 after 0 votes]
5498392
Wilding
422/68.1
Mar,1996

[0 after 0 votes]
5443890
Ohman
428/167
Aug,1995

[0 after 0 votes]
5376252
Ekstrom
204/603
Dec,1994

[0 after 0 votes]
5304487
Wilding
435/29
Apr,1994

[0 after 0 votes]
5252294
Kroy
422/102
Oct,1993

[0 after 0 votes]
5229297
Schnipelsky
436/94
Jul,1993

[0 after 0 votes]
5126022
Soane
204/458
Jun,1992

[0 after 0 votes]
4908112
Pace
210/198.2
Mar,1990

[0 after 0 votes]
4534659
Dourdeville
366/338
Aug,1985

[0 after 0 votes]
4390403
Batchelder
204/547
Jun,1983

[0 after 0 votes]
 Foreign References
 Other References
 Market Review Submit all comments and votes
   
Market Size
Estimate the gross annual revenues of the relevant market sector:
> $10B
$5B - $10B
$2B - $5B
$500M - $2B
$100M - $500M
$10M - $100M
$1M - $10M
$500K - $1M
$100K - $500K
< $100K
[No votes]
$0
 
$0   $2.5B   $5B   $7.5B   $10B
Market Share
Estimate the percentage of the relevant market sector this invention will capture:
75% - 100%
50% - 74.99%
25% - 49.99%
10 - 24.99%
5 - 9.99%
2 - 4.99%
1 - 1.99%
< 1%
[No votes]
0.0%
 
0%   25%   50%   75%   100%
Reasonable Royalty
What percentage of gross sales should the inventor or assignee be paid?
75% - 100%
50% - 74.99%
25% - 49.99%
10 - 24.99%
5 - 9.99%
2 - 4.99%
1 - 1.99%
< 1%
[No votes]
0.0%
 
0%   25%   50%   75%   100%
Public's "Guesstimation" of Royalty Value
Market SizeN/A[No votes]
xMarket ShareN/A[No votes]
xReasonable RoyaltyN/A[No votes]

N/A

License Availablity
If you are NOT the owner or assignee, answer here:
Yes, license is available for purchase

No, license is not currently available



[No votes]
License Availablity
If you ARE the owner or assignee, answer here:
Yes, license is available for purchase

No, license is not currently available



[No votes]
Competitive Advantage
Does this invention have a significant competitive advantage over similar technologies?
Yes

No



[No votes]
Most helpful competitive advantage comment
[No comments]

Commercial Alternatives
Are there viable commercial alternatives for this invention?
Yes

No



[No votes]
Most helpful commercial alternative comment
[No comments]

 Technical Review Submit all comments and votes
 Claims Submit all comments and votes
 


What is claimed is:

1. A mirofluidic device comprising a body structure and at least a first microscale channel disposed therein, the microscale channel comprising at least first and second ends and at least a portion of the microscale channel having an aspect ratio (width/depth) less than 1.

2. The microfluidic device of claim 1, further comprising an electrical controller operably linked to the first and second ends of the microscale channel, for applying a voltage gradient between the first and second ends.

3. The microfluidic device of claim 1, further comprising first and second reservoirs disposed in the body structure, the first and second reservoirs being in fluid communication with the first and second ends of the first microscale channel, respectively.

4. The microfluidic device of claim 1, wherein the microscale channel comprises at least one turn of at least 30.degree..

5. The microfluidic device of claim 1, wherein the microscale channel comprises at least one turn of at least 45.degree..

6. The microfluidic device of claim 1, wherein the microscale channel comprises at least one turn of at least 90.degree..

7. The microfluidic device of claim 6, wherein the microscale channel comprises at least two turns of at least 90.degree..

8. The microfluidic device of claim 1, wherein the microscale channel comprises at least one turn of at least 150.degree..

9. The microfluidic device of claim 8, wherein the microscale channel comprises at least two turns of at least 150.degree..

10. The microfluidic device of claim 1, wherein the microscale channel comprises at least one turn of about 180.degree..

11. The microfluidic device of claim 1, wherein the microscale channel comprises an aspect ratio less than or equal to about 0.5.

12. The microfluidic device of claim 1, wherein the microscale channel comprises an aspect ratio less than 0.2.

13. The microfluidic device of claim 1, wherein the microscale channel comprises an aspect ratio less than 0.1.

14. The microfluidic device of claim 1, wherein the at least one channel comprises a separation matrix disposed therein.

15. The microfluidic device of claim 14, wherein the separation matrix comprises an acrylamide polymer.

16. The microfluidic device of claim 14, wherein the separation matrix comprises a polymethylacrylamide polymer.

17. The microfluidic device of claim 1, further comprising at least a second microscale channel having first and second ends, the second microscale channel intersecting and in fluid communication with the first microscale channel.

18. The microfluidic device of claim 17, wherein the second microscale channel is in fluid communication with the first microscale channel at the second end of the second microscale channel.

19. The microfluidic device of claim 18, further comprising at least first, second and third reservoirs disposed in the body structure, the first and second reservoirs being in separate fluid communication with the first and second ends of the first microscale channel, respectively, and the third reservoir being in fluid communication with the first end of the second microscale channel.

20. The microfluidic device of claim 19, further comprising an electrical controller operably linked to each of the first, second and third reservoirs, the controller being capable of concomitantly delivering a voltage to each of the first, second and third reservoirs.

21. The microfluidic device of claim 19, further comprising a fourth reservoir disposed in the body structure, the fourth reservoir being in fluid communication with the second end of the second microscale channel.

22. The microfluidic device of claim 21, further comprising an electrical controller operably coupled to each of the first, second, third and fourth reservoirs, the controller being capable of concomitantly delivering a voltage to each of the first, second, third and fourth reservoirs.

23. The microfluidic device of claim 18, wherein the second microscale channel is in fluid communication with the first microscale channel between the first and second ends of the second microscale channel.

24. The microfluidic device of claim 1, wherein the body structure comprising the first microscale channel is fabricated from a polymeric material.

25. The microfluidic device of claim 24, wherein the body structure is injection molded from the polymeric material.

26. The microfluidic device of claim 24, wherein the first microscale channel is embossed into a polymeric substrate.

27. The microfluidic device of claim 24, wherein the polymeric material is selected from polymethylmethacrylate (PMMA), polycarbonate, polytetrafluoroethylene, polyvinylchloride (PVC), polydimethylsiloxane (PDMS) and polysulfone.

28. A microfluidic system, comprising:

a microfluidic device comprising a body structure, the body structure having at least first and second microscale channels disposed therein, each of the first and second microscale channels having first and second ends, the first microscale channel intersecting and in fluid communication with the second channel, at least the first microscale channel having an aspect ratio (width/depth) less than or equal to about 1; and

an electrical control system operably coupled to the first and second ends of the first and second channels, and capable of concomitantly delivering a voltage to each of the first and second ends of the first and second channels.

29. The microfluidic system of claim 28, wherein the body structure is fabricated from a polymeric material.

30. The microfluidic device of claim 29, wherein the polymeric material is selected from polymethylmethacrylate (PMMA), polycarbonate, polytetrafluoroethylene, polyvinylchloride (PVC), polydimethylsiloxane (PDMS) and polysulfone.

31. A method of transporting at least a first material region through a microscale channel wherein the channel comprises at least one turn, the method comprising:

providing at least a portion of the channel at the turn with an aspect ratio (width/depth) that is less than 1; and

transporting the first material region through the at least one turn.

32. The method of claim 31, further comprising transporting at least a second material region through the first microscale channel.

33. The method of claim 31, wherein the at least one channel comprises a separation matrix disposed therein, the first and second material regions comprise first and second species bands, separated in the at least one channel, and the step of transporting comprises applying a voltage gradient along the length of the first microscale channel.

34. The method of claim 31, wherein the step of transporting the first material region through the channel turn is carried out whereby the portion of the material region traveling at the inside edge of the channel turn traverses the turn at substantially the same rate as the portion of the material region at the outside edge of the channel turn.

35. A method of mixing a first material and at least a second material in a first microscale channel, comprising:

providing a mixing region and a non-mixing region of the first channel, the mixing region having a cross-sectional area that is sufficient to permit substantially complete diffusional mixing of the two materials while the two materials are serially transported into and through the mixing region; and

serially introducing and transporting the two materials into and through the mixing region.

36. A method of mixing according to claim 35, wherein the first material and at least a second material in a microfluidic device at a preselected ratio, comprising:

introducing a first of the two materials into the mixing region at a first flow rate for a first selected time;

introducing a second of the two materials into the mixing region at the second flow rate for a second selected time, wherein the ratio of the first selected time times the first flow rate, to the second selected time times the second flow rate, is equal to the preselected ratio; and

wherein the mixing channel includes a region having a cross-sectional area that is sufficient to permit substantially complete diffusional mixing of the first and second materials within the mixing channel.

37. The method of claim 36, wherein the first flow rate and second flow rate are substantially equal, and the ratio of the first selected time to the second selected time is equal to the preselected ratio.

38. The method of claim 35, wherein the mixing region of the first channel has a width equal to the non-mixing portion of the first channel and a depth that is at least twice a depth of the non-mixing region of the first channel.

39. The method of claim 35, wherein the mixing region of the first channel has an aspect ratio (width/depth) of less than 1.

40. The method of claim 35, wherein the mixing region of the first channel has an aspect ratio (width/depth) of less than about 0.5.

41. The method of claim 35, wherein the mixing region of the first channel has an aspect ratio (width/depth) of less than about 0.2.

42. The method of claim 35, wherein the mixing region of the first channel has an aspect ratio (width/depth) of less than 0.1.
 Description Submit all comments and votes
 


BACKGROUND OF THE INVENTION

Microfluidic devices and systems have been gaining substantial interest as they are increasingly being demonstrated to be robust, highly accurate, high throughput and low cost methods of performing previously cumbersome and or expensive analytical operations.

In particular, microfluidic systems have been described for use in ultra high throughput screening assay systems, e.g., for pharmaceutical discovery, diagnostics and the like. See International Application No. PCT/US97/10894 filed Jun. 28, 1997 (Attorney Docket No. 17646-000420PC). In addition, such microfluidic systems have reportedly been used in performing separations-based analyses, e.g., nucleic acid separations, etc. See, e.g., Woolley et al., Proc. Nat'l Acad. Sci., USA 91:11348-11352 (1994).

Despite the promise of microfluidic systems in terms of throughput, automatability and cost, many of the systems that have been described suffer from substantial drawbacks. Initially, many of these systems have substantial reductions in resolution over their counterpart methods on the bench top. In particular, a number of relatively minor considerations can readily become major factors when considered in the context of the relatively small amounts of material transported through these systems. For example, in microfluidic channels that include curves or turns, variations in distances through these turns and curves at the inside and outside edges can substantially affect the resolution of materials transported through these channels.

Further, simple operations, such as dilution and mixing have generally been accomplished at the expense of overall device volume, e.g., adding to the reagent/material volume required for carrying out the overall function of the device. In particular, such mixing typically requires much larger chambers or channels in order to provide adequate mixing of reagents or diluents within the confines f the microfluidic systems.

Thus, it would be generally desirable to provide microfluidic systems that are capable of capitalizing upon the myriad benefits described above, without sacrificing other attributes, such as resolution volume, and the like. The present invention meets these and other needs.

SUMMARY OF THE INVENTION

The present invention generally provides microfluidic devices, systems and methods of using these devices and systems. The microfluidic devices and systems generally incorporate improved channel profiles that result in substantial benefits over previously described microfluidic systems.

For example, in one embodiment, the present invention provides microfluidic devices and systems incorporating them, which devices comprise a body structure and at least a first microscale channel disposed therein. The microscale channel typically comprises at least first and second ends and at least a portion of the microscale channel having an aspect ratio (width/depth) less than 1. In preferred aspects, the devices and systems include an electrical controller operably linked to the first and second ends of the microscale channel, for applying a voltage gradient between the first and second ends, and/or are fabricated from polymeric materials.

In a related but alternate embodiment, the present invention provides microfluidic devices and systems that comprise a body structure having at least a first microscale channel disposed therein, where the microscale channel has at least one turning portion incorporated therein. In this embodiment, the turning portion of the channel comprises a varied depth across its width, where the varied depth is shallower at an outside edge of the turning portion than at an inside edge of the turning portion. Preferably, the relative depths at the inside edge and outside edge of the turning portion of the channel are selected whereby the time required for a material traveling through the turning portion at the outside edge is substantially equivalent to a time required for the material to travel through the turning portion at the inside edge.

As alluded to above, the present invention also comprises microfluidic systems that include the above described microfluidic devices in combination with an electrical control system. The electrical control system is operably coupled to the first and second ends of the first and second channels, and capable of concomitantly delivering a voltage to each of the first and second ends of the first and second channels.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 schematically illustrates a microfluidic device fabricated from a planar substrate.

FIGS. 2A and 2B illustrate the distortion of material regions or plugs when transported through a typical, curved microfluidic channel. FIG. 2A illustrates distortion for a single material region, while FIG. 2B illustrates distortion for multiple separate species regions or bands, such as in electrophoretic separations analysis, as well as exemplary signal, e.g., fluorescent signal that would be obtained from such species bands, both before and after the distorting effects of the channel curves.

FIG. 3 illustrates a diagram of an electric field applied across the length of a turning microscale channel.

FIG. 4 illustrates a comparison of a channel having a shallow aspect ratio, e.g., >1 (width/depth)(top), as well as a channel having a deep aspect ratio, e.g., <1 (width/depth)(bottom).

FIGS. 5A and 5B illustrate microscale channels having a varied depth to permit improved material intermixing.

DETAILED DESCRIPTION OF THE INVENTION

I. General

A. Introduction

The present invention is generally directed to improved microfluidic devices, systems and methods of using same, which incorporate channel profiles that impart significant benefits over previously described systems. In particular, the presently described devices and systems employ channels having, at least in part, depths that are varied over those which have been previously described. These varied channel depths provide numerous beneficial and unexpected results.

As used herein, the term "microscale" or "microfabricated" generally refers to structural elements or features of a device which have at least one fabricated dimension in the range of from about 0.1 .mu.m to about 500 .mu.m. Thus, a device referred to as being microfabricated or microscale will include at least one structural element or feature having such a dimension. When used to describe a fluidic element, such as a passage, chamber or conduit, the terms "microscale," "microfabricated" or "microfluidic" generally refer to one or more fluid passages, chambers or conduits which have at least one internal cross-sectional dimension, e.g., depth, width, length, diameter, etc., that is less than 500 .mu.m, and typically between about 0.1 .mu.m and about 500 .mu.m. In the devices of the present invention, the microscale channels or chambers preferably have at least one cross-sectional dimension between about 0.1 .mu.m and 200 .mu.m, more preferably between about 0.1 .mu.m and 100 .mu.m, and often between about 0.1 .mu.m and 20 .mu.m. Accordingly, the microfluidic devices or systems prepared in accordance with the present invention typically include at least one microscale channel, usually at least two intersecting microscale channels, and often, three or more intersecting channels disposed within a single body structure. Channel intersections may exist in a number of formats, including cross intersections, "T" intersections, or any number of other structures whereby two channels are in fluid communication.

The body structure of the microfluidic devices described herein typically comprises an aggregation of two or more separate layers which when appropriately mated or joined together, form the microfluidic device of the invention, e.g., containing the channels and/or chambers described herein. Typically, the microfluidic devices described herein will comprise a top portion, a bottom portion, and an interior portion, wherein the interior portion substantially defines the channels and chambers of the device. For example, typically, the body structure is fabricated from at least two substrate layers that are mated together to define the channel networks of the device, e.g., the interior portion. In preferred aspects, the bottom portion of the device comprises a solid substrate that is substantially planar in structure, and which has at least one substantially flat upper surface.

A variety of substrate materials may be employed as the bottom portion. Typically, because the devices are microfabricated, substrate materials will be selected based upon their compatibility with known microfabrication techniques, e.g., photoliphography, wet chemical etching, laser ablation, air abrasion techniques, LIGA, reactive ion etching (RIE), injection molding, embossing, and other techniques. The substrate materials are also generally selected for their compatibility with the full range of conditions to which the microfluidic devices may be exposed, including extremes of pH, temperature, salt concentration, and application of electric fields. Accordingly, in some preferred aspects, the substrate material may include materials normally associated with the semiconductor industry in which such microfabrication techniques are regularly employed, including, e.g., silica based substrates, such as glass, quartz, silicon or polysilicon, as well as other substrate materials, such as gallium arsenide and the like. In the case of semiconductive materials, it will often be desirable to provide an insulating coating or layer, e.g., silicon oxide, over the substrate material, and particularly in those applications where electric fields are to be applied to the device or its contents.

In particularly preferred aspects, the substrate materials will comprise polymeric materials, e.g., plastics, such as polymethylmethacrylate (PMMA), polycarbonate, polytetrafluoroethylene (TEFLON.TM.), polyvinylchloride (PVC), polydimethylsiloxane (PDMS), polysulfone, and the like. Such polymeric substrates are readily manufactured using available microfabrication techniques, as described above, or from microfabricated masters, using well known molding techniques, such as injection molding, embossing or stamping, or by polymerizing the polymeric precursor material within the mold (See U.S. Pat. No. 5,512,131). Such polymeric substrate materials are preferred for their ease of manufacture, low cost and disposability, as well as their general inertness to most extreme reaction conditions. Again, these polymeric materials may include treated surfaces, e.g., derivatized or coated surfaces, to enhance their utility in the microfluidic system, e.g., provide enhanced fluid direction, e.g., as described in U.S. patent application Ser. No. 08/843,212, filed Apr. 14, 1997, and which is incorporated herein by reference in its entirety for all purposes.

An example of a microfluidic device fabricated from a planar substrate is illustrated in FIG. 1. Briefly, the channels and/or chambers of the device 100 are typically fabricated into or upon a flat surface of a planar substrate 102. The channels and/or chambers of the device may be fabricated using a variety of methods whereby these channels and chambers are defined between two opposing substrates. For example, the channels, e.g. channels 104 and 106, and/or chambers of the microfluidic devices are typically fabricated into the upper surface of the bottom substrate or portion, as microscale grooves or indentations, using the above described microfabrication techniques. Alternatively, raised regions may be fabricated onto the planar surface of the bottom portion or substrate in order to define the channels and/or chambers. The top portion or substrate (not separately shown) also comprises a first planar surface, and a second surface opposite the first planar surface. In the microfluidic devices prepared in accordance with the methods described herein, the top portion also includes a plurality of apertures, holes or ports 110-116 disposed therethrough, e.g., from the first planar surface to the second surface opposite the first planar surface.

The first planar surface of the top substrate is then mated, e.g., placed into contact with, and bonded to the planar surface of the bottom substrate, covering and sealing the grooves and/or indentations in the surface of the bottom substrate, to form the channels and/or chambers (i.e., the interior portion) of the device at the interface of these two components. The holes 110-116 in the top portion of the device are oriented such that they are in communication with at least one of the channels, e.g., 104 or 106, and/or chambers formed in the interior portion of the device from the grooves or indentations in the bottom substrate. In the completed device, these holes 110-116 function as reservoirs for facilitating fluid or material introduction into the channels or chambers of the interior portion of the device, as well as providing ports at which electrodes may be placed into contact with fluids within the device, allowing application of electric fields along the channels of the device to control and direct fluid transport within the device. As shown, channel 104, which serves as the main or analysis channel in the device shown, intersects channel 106, which serves as a sample introduction channel, at intersection 108. The analysis channel 104, also includes a serpentine portion 118, which serves to extend the length of the analysis channel without requiring substantially greater substrate area.

In many embodiments, the microfluidic devices will include an optical detection window 120 disposed across one or more channels and/or chambers of the device. Optical detection windows are typically transparent such that they are capable of transmitting an optical signal from the channel/chamber over which they are disposed. Optical detection windows may merely be a region of a transparent cover layer, e.g., where the cover layer is glass or quartz, or a transparent polymer material, e.g., PMMA, polycarbonate, etc. Alternatively, where opaque substrates are used in manufacturing the devices, transparent detection windows fabricated from the above materials may be separately manufactured into the device.

These devices may be used in a variety of applications, including, e.g., the performance of high throughput screening assays in drug discovery, immunoassays, diagnostics, nucleic acid analysis, including genetic analysis, and the like. As such, the devices described herein, will often include multiple sample introduction ports or reservoirs, for the parallel or serial introduction and analysis of multiple samples, e.g., as described in U.S. patent application Ser. No. 08/845,754, filed Apr. 25, 1997, and incorporated herein by reference. Alternatively, these devices may be coupled to a sample introduction port, e.g., a pipettor, which serially introduces multiple samples into the device for analysis. Examples of such sample introduction systems are described in e.g., U.S. patent application Ser. Nos. 08/761,575 and 08/760,446 (Attorney Docket Nos. 17646-000410 and 17646-000510, respectively) each of which was filed on Dec. 6, 1996, and is hereby incorporated by reference in its entirety for all purposes.

II. Channel Aspect Ratios

In a first aspect, the present invention provides microfluidic devices and systems that comprise a body structure which has disposed therein, at least one microscale channel or channel portion, which channel or channel portion has an aspect ratio that is substantially the inverse of previously described microscale channels.

In particular, microscale channels which have been described for use in microfluidic systems, typically have employed channel dimensions in the range of from about 50 to about 200 .mu.m wide and from about 5 to about 20 .mu.m deep. In any event, the aspect ratios of these channels (width/depth) is well in excess of 2 and typically is in the range of from about 7 to about 10. These aspect ratios have likely resulted, at least in part, from the processes involved in the fabrication of microfluidic systems, and particularly, the microscale channels incorporated therein. Specifically, such channels are often fabricated in silicon based substrates, such as glass, quartz, silicon, etc., using photolithographic techniques. The chemistries involved in such techniques are readily used to fabricate channels having widths and depths in the above-described ranges. However, because these techniques involve etching processes, i.e., using generally available isotropic etching chemicals e.g., hydrofluoric acid (HF), they are generally not as effective in producing channels having depths substantially greater than those described, due to the increased etching time required. Specifically, isotropic agents typically etch uniformly in all directions on amorphous substrates, i.e., glass. In such instances, it becomes effectively impossible to produce channels having aspect ratios less than 1.

Microfluidic devices incorporating the above-described dimensions and aspect ratios, have proven very useful in a wide variety of important analytical applications. These applications include high-throughput screening of pharmaceutical and other test compounds (See commonly assigned U.S. application Ser. No. 08/761,575, filed Dec. 6, 1996), nucleic acid analysis, manipulation and separation (See commonly assigned U.S. application Ser. Nos. 08/835,101 and 08/845,754, filed Apr. 4, 1997 and Apr. 25, 1997, respectively), and more.

Despite the substantial utility of these systems, the present inventors have identified some potential shortcomings of microscale channels having the above-described dimensions, particularly where it is desired to transport a given material region over a substantial distance within these channels.

In a first particular example, because microfluidic systems are typically fabricated within body structures that have relatively small areas, it is generally desirable to maximize the use of the space within the body structure. As such, channels often incorporate geometries that include a number of channel turns or corners, e.g., serpentine, saw-tooth etc. The incorporation of such channel turns can have adverse effects on the ability of discrete material regions to maintain their cohesion. In particular, in a turning microscale channel, material travelling along the outside edge traverses the turn much more slowly than material travelling at the inside edge, imitating a "race-track" effect. This effect is at least in part due to the greater distance, or in the case of a three dimension fluidic system, the greater volume a material must travel through at the outside edge of a channel as opposed to the inner edge of the channel. This difference in traversal time can result in a substantial perturbation or distortion of a discrete, cohesive material plug or region in a microscale channel.

A schematic illustration of this sample perturbation resulting from turns or curves in microscale channels is provided in FIG. 2A. Briefly, FIG. 2A illustrates a discrete material region 204, e.g., a sample plug, species band or the like, travelling through a microscale channel 202. In the straight portions of the channel, the material region substantially maintains its shape with a certain level of diffusion. However, once the material region travels around a curve in the channel, the differences in flow rate through the channel at different points across the channel's width, result in a distorted material region 206.

The distortion of these material regions can adversely effect the resolution with which the particular material region is transported through the turning channel. This is particularly problematic, for example, in separation applications, e.g., protein or nucleic acid electrophoresis, where the goal is to separate a given material into its constituent elements, and to separately detect those elements. Further, such separation applications typically require substantially longer separation channels or columns, thereby increasing the number of channel turns to which a particular material will be subjected. This separate detection typically requires that the elements be maintained as well resolved material regions. FIG. 2B illustrates an exemplary separation channel incorporating a channel turn. The separated species bands 214 substantially maintain their shape and separation within the straight portions of channel 202. The well-resolved character of the species bands 214 is illustrated by the signal graph 216. After having traveled through the curved section of the channel, the species bands 218 show substantial distortion. Further, as indicated by the signal graph 220, the resolution of these bands, and thus their detectability, is substantially reduced.

This material region distortion, or sample perturbation, also becomes a problem where one wishes to separately transport materials through a microfluidic system, e.g., for separate analysis. Examples of such applications include high-throughput experimentation, e.g., screening, diagnostics, and the like. In particular, maintaining different materials, e.g. samples, as well-resolved plugs of material, i.e., without the above-described distortion effects, allows multiple plugs to be moved through a system without fear of intermixing. This also prevents the excess, uncontrolled dilution of those samples, resulting from the distortion effects.

In certain preferred aspects, the microfluidic devices and systems described herein, employ electrokinetic material transport systems for moving and directing material through and among the microscale channel networks that are incorporated in the microfluidic devices. Unfortunately, however, the level of sample perturbation is substantially increased in microfluidic systems that employ such electrokinetic material transport.

As used herein, "electrokinetic material transport systems" include systems which transport and direct materials within an interconnected channel and/or chamber containing structure, through the application of electrical fields to the materials, thereby causing material movement through and among the channel and/or chambers, i.e., cations will move toward the negative electrode, while anions will move toward the positive electrode.

Such electrokinetic material transport and direction systems include those systems that rely upon the electrophoretic mobility of charged species within the electric field applied to the structure. Such systems are more particularly referred to as electrophoretic material transport systems. Other electrokinetic material direction and transport systems rely upon the electroosmotic flow of fluid and material within a channel or chamber structure which results from the application of an electric field across such structures. In brief, when a fluid is placed into a channel which has a surface bearing charged functional groups, e.g., hydroxyl groups in etched glass channels or glass microcapillaries, those groups can ionize. In the case of hydroxyl functional groups, this ionization, e.g., at neutral pH, results in the release of protons from the surface and into the fluid, creating a concentration of protons at near the fluid/surface interface, or a positively charged sheath surrounding the bulk fluid in the channel. Application of a voltage gradient across the length of the channel, will cause the proton sheath to move in the direction of the voltage drop, i.e., toward the negative electrode.

"Controlled electrokinetic material transport and direction," as used herein, refers to electrokinetic systems as described above, which employ active control of the voltages applied at multiple, i.e., more than two, electrodes. Rephrased, such controlled electrokinetic systems concomitantly regulate voltage gradients applied across at least two intersecting channels. Controlled electrokinetic material transport is described in Published PCT Application No. WO 96/04547, to Ramsey, which is incorporated herein by reference in its entirety for all purposes. In particular, the preferred microfluidic devices and systems described herein, include a body structure which includes at least two intersecting channels or fluid conduits, e.g., interconnected, enclosed chambers, which channels include at least three unintersected termini. The intersection of two channels refers to a point at which two or more channels are in fluid communication with each other, and encompasses "T" intersections, cross intersections, "wagon wheel" intersections of multiple channels, or any other channel geometry where two or more channels are in such fluid communication. An unintersected terminus of a channel is a point at which a channel terminates not as a result of that channel's intersection with another channel, e.g., a "T" intersection. In preferred aspects, the devices will include at least three intersecting channels having at least four unintersected termini. In a basic cross channel structure, where a single horizontal channel is intersected and crossed by a single vertical channel, controlled electrokinetic material transport operates to controllably direct material flow through the intersection, by providing constraining flows from the other channels at the intersection. For example, assuming one was desirous of transporting a first material through the horizontal channel, e.g., from left to right, across the intersection with the vertical channel. Simple electrokinetic material flow of this material across the intersection could be accomplished by applying a voltage gradient across the length of the horizontal channel, i.e., applying a first voltage to the left terminus of this channel, and a second, lower voltage to the right terminus of this channel, or by allowing the right terminus to float (applying no voltage). However, this type of material flow through the intersection would result in a substantial amount of diffusion at the intersection, resulting from both the natural diffusive properties of the material being transported in the medium used, as well as convective effects at the intersection.

In controlled electrokinetic material transport, the material being transported across the intersection is constrained by low level flow from the side channels, e.g., the top and bottom channels. This is accomplished by applying a slight voltage gradient along the path of material flow, e.g., from the top or bottom termini of the vertical channel, toward the right terminus. The result is a "pinching" of the material flow at the intersection, which prevents the diffusion of the material into the vertical channel. The pinched volume of material at the intersection may then be injected into the vertical channel by applying a voltage gradient across the length of the vertical channel, i.e., from the top t