Chemistry: electrical and wave energy – Processes and products – Electrophoresis or electro-osmosis processes and electrolyte...
Reexamination Certificate
1999-10-12
2002-09-10
Tung, T. (Department: 1743)
Chemistry: electrical and wave energy
Processes and products
Electrophoresis or electro-osmosis processes and electrolyte...
C204S604000, C204S601000, C073S864010, C073S864020, C436S180000, C422S091000, C422S105000
Reexamination Certificate
active
06447661
ABSTRACT:
BACKGROUND OF THE INVENTION
In the pharmaceutical discovery process, high-throughput screening methods and systems have been touted as one method among many, for at least initially identifying promising new pharmaceutical candidate compounds. These methods and systems have been described for use in conjunction with, or even in place of, more traditional rational drug design procedures and methods.
In the past, high-throughput screening operations have simply involved the incorporation of very complex automation elements, e.g., robotics and multiplexed fluid handling systems, in order to carry out assay methods developed for use with conventional technologies, but in massively parallel experiments. Specifically, large numbers of standard assays are carried out in multi-well assay plates into which reagents are dispensed using the automated and highly parallelized fluid handling systems and robotic plate handling equipment. While such systems have increased the number of different materials that can be screened, these systems tend to be extremely complex, relatively unreliable, and have large space, reagent and cost requirements for acquiring and maintaining the overall systems.
Microfluidic devices and systems have been described as potential avenues for performing these high-throughput screening operations while minimizing the space, reagent and cost requirements of the overall systems. However, such systems have largely failed in this respect due to an inability to conveniently introduce large numbers of different reagents into the microfluidic systems. Specifically, such systems have generally relied upon conventional, large, expensive fluid handling systems to introduce samples and reagents into reservoirs on microfluidic devices, effectively ‘giving back’ any cost or space advantages that would have been realized.
U.S. Pat. No. 5,779,868, and Published International Patent Application Nos. 98/00705 and 98/00231, on the other hand, describe microfluidic devices and systems for use in performing ultra high-throughput screening assays, which devices and systems incorporate an integrated sampling system, or “world to chip” interface, for accessing external materials and delivering them onto the device or LabChip™. These systems typically incorporate a sampling pipettor integrated into the microfluidic system for directly accessing samples, reagents and other materials from sources of such materials, e.g., compound libraries, etc. Integrated pipettor systems have generally proven very effective in rapidly, efficiently and accurately accessing large numbers of different reagents and transporting those reagents into analytical channels.
Despite the effectiveness of these integrated pipettor systems in microfluidic applications, it would generally be desirable to provide such systems with improved structural, interfacing and flow characteristics. The present invention meets these and a variety of other needs.
SUMMARY OF THE INVENTION
The present invention provides new and useful improvements to external material sampling or accession systems for microfluidic devices and systems, which provide for improved structural characteristics and improved interfacing.
In a first aspect, the invention provides methods of sampling fluids, e.g., using spontaneous injection. These methods comprise dipping an open end of an open ended fluid-filled capillary element into a source of first fluid, withdrawing the capillary element from the first fluid, and permitting an amount of the first fluid remaining on the open ended capillary to spontaneously inject into the capillary channel. The capillary element is then dipped into a second fluid after a selected time period, where the selected time period is controlled to control the amount of the first fluid permitted to spontaneously inject into the open ended capillary channel.
Another aspect of the invention is a method of introducing a first fluid into a microfluidic device, comprising providing a microfluidic device having a body structure with at least first and second intersecting microscale channels disposed therein, and a capillary element extending from the body structure. The capillary element has first and second ends and a capillary channel disposed through it that is open at the first end, and in fluid communication with at least one of the first and second intersecting microscale channels in the body structure at the second end of the capillary element. The first end of the capillary channel is dipped into a source of the first fluid and then withdrawn, permitting an amount of the first fluid on the first end of the capillary channel to spontaneously inject into the capillary channel. The amount of first fluid injected into the capillary channel is transported into at least one of the first and second microscale channels that are disposed in the body structure.
Another aspect of the invention is a method of reducing or eliminating spontaneous injection. The method comprises dipping a capillary into a source of a first fluid and applying a negative pressure to draw the first fluid into the capillary. The negative pressure is then changed to a positive or negative pressure, thus eliminating the spontaneous injection of the fluid at the tip of the capillary when it is removed from the source of the first fluid. The capillary, which is under a positive or zero pressure, is then optionally dipped into a source of a second fluid. The pressure is changed back to a negative pressure, thus drawing the second fluid into the capillary. The pressure changes are typically made at substrate and enzyme wells as well.
Another aspect of the invention is a method of screening one or more samples. One or more samples are introduced into a microfluidic system and one or more inactivating reagents are added either before a sample, after a sample, or between two samples. The inactivating reagent completely blocks the activity of an enzyme in an enzymatic assay and provides calibration of the percent inhibition level in an assay.
Methods of spatially separating one or more samples in a microfluidic channel are also provided. The method comprises flowing one or more samples through a microscale channel. Spacers are flowed through the channel between the samples to separate one sample from another. The spacers typically comprise a volume of air or an immiscible fluid. The volume of air or immiscible fluid is typically flowed through the microscale channel after each sample or before each sample.
In still another aspect, the present invention provides a microfluidic device that comprises a planar substrate having disposed therein an integrated channel structure that has at least first and second intersecting microscale channels included within. At least the first channel terminates in a substantially rectangular opening in the body structure. The device also includes a capillary element having a capillary channel running through it. At least one end of the capillary element is substantially rectangular. The substantially rectangular end of the capillary element is inserted into the substantially rectangular opening in the body structure and positioned such that the capillary channel in the capillary element is in fluid communication with the at least first microscale channel in the body structure.
The present invention also provides a method of joining a capillary element to a microfluidic device having an integrated channel network. The method comprises providing a microfluidic device having a body structure with at least first and second intersecting microscale channels included within, and having a substantially rectangular opening disposed in the body structure, at least one of the first and second microscale channels terminating in and being in communication with the opening. The method provides a substantially rectangular capillary element having first and second ends and a capillary channel running through the capillary element from the first end to the second end, and wherein the second end has a substantially rectangular shape. The second end of a capilla
Chien Ring-Ling
Chow Andrea W.
Dubrow Robert S.
Gallagher Steven James
Knapp Michael R.
Caliper Technologies Corp.
Landry Stacy
Noguerola Alex
Quine Jonathan Alan
Quine Intellectual Property Law Group P.C.
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