Liquid purification or separation – With means to add treating material – Chromatography
Reexamination Certificate
2002-04-05
2004-06-22
Therkorn, Ernest G. (Department: 1723)
Liquid purification or separation
With means to add treating material
Chromatography
C210S656000
Reexamination Certificate
active
06752922
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a microfluidic device comprising a microfabricated fluid delivery system and a chromatography column. In particular, the present invention relates to a microfluidic device comprising an OTLC column, PCLC column, or combinations thereof, which is operatively interconnected to a microfabricated fluid delivery system.
BACKGROUND OF THE INVENTION
Microfluidic devices allow manipulation of extremely small volumes of liquids, and therefore are particularly useful in small scale sample preparations, chemical synthesis, sample assay, sample screening, and other applications where a micro-scale amount of samples are involved. For many applications, the chemical make up of the resulting material (i.e., sample) needs to be analyzed. Such analysis typically requires at least some degree of sample purification and/or separation. However, due to the small sample size (e.g., nanoliter to microliter) used by these microfluidic devices, conventional separation techniques are not applicable.
Use of packed capillary and open tubular liquid chromatography (PCLC and OTLC, respectively) separation techniques have become increasingly popular due to the demonstrated means of achieving high chromatography efficiency with low operation pressures. Conventional high performance liquid chromatography (i.e., HPLC) typically requires >2000 psi pressure. In contrast, pressure of as low as 5 psi can be used for OTLC and PCLC. Some of the advantages of the OTLC and PCLC techniques include, but are not limited to: (1) an increased efficiency, (2) a lower sample dilution requirement, thereby increasing the sample detection sensitivity, e.g., using a mass spectrometer, (3) a smaller amount of eluent requirement, and (4) the small sample amount requirement. The latter advantage is of particularly importance in a variety of fields, such as proteomics, genomics, forensics, and other areas where a minute quantity of sample is to be separated or purified. Unfortunately, in order to achieve the desired sensitivity and efficiency in OTLC and PCLC, the inner diameter of OTLC and PCLC columns need to be small, generally in the order of 50 &mgr;m or less, and preferably about 10 &mgr;m or less. The small column diameter size in OTLC and PCLC techniques requires an equally precise sample injection and pumping system. To be effective, OTLC and PCLC techniques require a sample flow rate of 0.01 &mgr;L/min or less. Conventional sample pumping system can not adequately meet this stringent requirement. In addition, difficulties with large interconnection dead volume and detection volume between the OTLC or PCLC column and the fluid delivery (i.e., pumping) system have greatly limited the application of OTLC and PCLC techniques.
Therefore, there is a need for OTLC and PCLC devices which comprise a sample injection and fluid pumping system that can achieve a sample flow rate of 0.01 &mgr;L/min or less. There is also a need for OTLC and PCLC devices which have small or no dead volume between the OTLC or PCLC column and the fluid delivery system.
SUMMARY OF THE INVENTION
One aspect of the present invention provides a microfluidic chromatography apparatus for separating an analyte in a sample fluid. The microfluidic chromatography apparatus of the present invention comprises a microfabricated fluid delivery system and a chromatography column. The microfabricated fluid delivery system of the present invention is capable of pumping a minute amount of fluid through the chromatography column. Preferably, the microfabricated fluid delivery system is capable of pumping (i.e., delivering or transporting) a fluid through the chromatography column at a flow rate of 0.01 &mgr;L/min or less. Thus, microfluidic chromatography apparatuses of the present invention are particularly useful in separating analyte(s) from a minute quantity of sample fluid.
Preferably, the fluid delivery system of the present invention is produced from a material comprising an elastomeric polymer. In one particular embodiment, the elastomeric polymer is selected from the group consisting of poly(carborane-siloxanes), poly(bis(fluoroalkoxy)phosphazene), poly(acrylonitrile-butadiene), poly(1-butene), poly(chlorotrifluoroethylene-vinylidene fluoride) copolymers, poly(ethyl vinyl ether), poly(vinylidene fluoride), poly(vinylidene fluoride-hexafluoropropylene) copolymer, elastomeric polyvinylchloride, polysulfone, polycarbonate, polymethylmethacrylate, polytertrafluoroethylene, polydimethylsiloxane, polydimethylsiloxane copolymer, and aliphatic urethane diacrylate.
The fluid deliver system of the present invention comprises:
(i) a microfluidic flow channel comprising a flow channel inlet for introducing the fluid into said flow channel and a flow channel outlet,
(ii) a flow control channel,
(iii) a flow control valve comprised of a flow control elastomeric segment that is disposed in between said flow channel and said flow control channel to regulate fluid flow through said flow channel, wherein said flow control valve is deflectable into or retractable from said flow channel upon which said flow control valve operates in response to an actuation force applied to said flow control channel, said flow control elastomeric segment when positioned in said flow channel restricting fluid flow therethrough, and
(iv) a flow control channel actuation system operatively interconnected to said flow control channel for applying an actuation force to said flow control channel.
The fluid delivery system of the present invention can further comprise other component(s) depending on a particular need. For example, in one particular embodiment, the fluid delivery system further comprises a peristaltic pump which is comprised of one or more of the flow control valves.
The fluid delivery system can also comprise an eluent inlet which is in fluid communication with the flow channel inlet for introducing an eluent to said flow channel. In one specific embodiment, the eluent inlet further comprises:
an eluent reservoir comprising an eluent reservoir inlet channel;
an eluent reservoir inlet control channel;
an eluent reservoir inlet control valve for opening and closing fluid communication between said eluent reservoir and said flow channel, wherein said eluent reservoir inlet control valve comprises an elastomeric segment of said eluent reservoir inlet control channel that is disposed in between said eluent reservoir inlet control channel and said eluent reservoir inlet channel to regulate fluid flow through said eluent reservoir inlet channel, wherein said eluent reservoir inlet control valve is deflectable into or retractable from said eluent reservoir inlet channel upon which said eluent reservoir inlet control valve operates in response to an actuation force applied to said eluent reservoir inlet control channel, said elastomeric segment of said eluent reservoir inlet control valve when positioned in said eluent reservoir inlet channel restricting fluid flow therethrough;
an eluent reservoir inlet control channel actuation system operatively interconnected to said eluent reservoir inlet control channel for applying an actuation force to said eluent reservoir inlet control channel.
The flow channel inlet of the fluid delivery system can also comprise:
a sample reservoir comprising a sample reservoir inlet channel which is in fluid communication with said flow channel;
a sample reservoir inlet control channel;
a sample reservoir inlet control valve for opening and closing fluid communication between said sample reservoir and said flow channel, wherein said sample reservoir inlet control valve comprises an elastomeric segment of said sample reservoir inlet control channel that is disposed in between said sample reservoir control channel and said sample reservoir inlet channel to regulate fluid flow through said sample reservoir inlet channel, wherein said sample reservoir inlet control valve is deflectable into or retractable from said sample reservoir inlet channel upon which said sample reservoir inlet control valve operates in response
Chou Hou-Pu
Huang Jiang
Unger Marc A.
Fluidigm Corporation
Therkorn Ernest G.
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