US20040257638A1 - Microfluidic analytical apparatus - Google Patents
Microfluidic analytical apparatus Download PDFInfo
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- US20040257638A1 US20040257638A1 US10/496,684 US49668404A US2004257638A1 US 20040257638 A1 US20040257638 A1 US 20040257638A1 US 49668404 A US49668404 A US 49668404A US 2004257638 A1 US2004257638 A1 US 2004257638A1
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- card
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L9/00—Supporting devices; Holding devices
- B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
- B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44704—Details; Accessories
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44756—Apparatus specially adapted therefor
- G01N27/44782—Apparatus specially adapted therefor of a plurality of samples
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44756—Apparatus specially adapted therefor
- G01N27/44791—Microapparatus
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00801—Means to assemble
- B01J2219/00804—Plurality of plates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00801—Means to assemble
- B01J2219/0081—Plurality of modules
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L2924/00—Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
- H01L2924/0001—Technical content checked by a classifier
- H01L2924/0002—Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00
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- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05K—PRINTED CIRCUITS; CASINGS OR CONSTRUCTIONAL DETAILS OF ELECTRIC APPARATUS; MANUFACTURE OF ASSEMBLAGES OF ELECTRICAL COMPONENTS
- H05K3/00—Apparatus or processes for manufacturing printed circuits
- H05K3/22—Secondary treatment of printed circuits
- H05K3/222—Completing of printed circuits by adding non-printed jumper connections
Abstract
A microfluidic analytical apparatus (10) comprising a microfluidic card pairing (12) with a corresponding circuit card (14) and the circuit card pairing (12) with corresponding conductive fingers (16). The microfluidic card (12) has a plurality of channels (32) and ports (54) on a top surface of the card in a desired configuration, the ports (54) in fluid communication with the channels (32). The circuit card (14) has a plurality of conductive pins (60) projecting from a bottom surface of the card and having a configuration that corresponds to the particular configuration of the ports (54) of the microfluidic card (12) that is paired with. The circuit card (14) is received within a holder (20) that provides that provides multiple functions. Conductive pads (18) are disposed on a top surface of the circuit card (14), the pads (18) in electrical communication with the conductive pins (60) and corresponding to a configuration of conductive fingers (16) connected to a power source to provide voltage to the microfluidic card (12) for analytical operations. Additionally, detection difficulties associates with non-uniformities present on the card surface are overcome using a detection system incorporating a compliantly mounted microscopic head.
Description
- This invention relates in general to microfluidic devices and analytical apparatus for using microfluidic devices to conduct chemical and biochemical sample analysis.
- Today's microfluidic chips are capable of reliably carrying out many chemical and reactions and analytical assays using minimal amounts reagents. These high throughput cards incorporate arrays of fluidic networks, each network having a multitude of ports or reservoirs and microchannels associated therewith. Examples of microfluidic chips, fluidic arrays, and their methods use are described in U.S. Pat. Nos. 5,750,015; 6,103,199 and published patent application 99/19717 assigned to the assignee and hereby incorporated by reference. In each network, reservoirs are provided for introduction of sample, reagents, test compounds, or liquid media. In some cases, microfluidic devices are manufactured with media already in the channels or reservoirs as appropriate.
- Microfluidic chips have been used for separation and analysis of nucleic acids, proteins and other molecules. By utilizing electrokinetic methods such capillary electrophoresis (CE), dielectrophoresis, and isoelectric focusing, components of a sample can be resolved and analyzed. One method of species detection involves conventional laser induced fluorescence, also known as LIF. A variety of mechanisms known in the art can be used for this purpose. For example, fluorescent detection mechanisms can be used in conjunction with confocal microscopy. Publications such as U.S. Pat. No. 5,296,703 and PCT WO 98/49543 describe systems for detecting fluorescent signals in microchannel arrays.
- Desirably, microfluidic chips can be manufactured from a variety of polymer materials leading to user convenience, disposability and affordability. These materials allow for standard manufacturing techniques including injection molding, compression molding, casting or hot embossing. One drawback however is that these methods all require heating and cooling of the chip substrate. Given variations between substrates in glass transition temperatures and varying exposure to both ambient and elevated temperatures, the resulting chips often include some level of warpage and/or minor defects. These irregularities can interfere with the intended operation of the chip. For example, detection systems may include robotics programmed to move to specific locations on a planar card. If the card is warped, these locations are difficult to reach or become inaccessible. Accordingly, it is desired to provide an accurate detection system that can compensate for inherent deficiencies in the microfluidic chip, such as warpage.
- Another issue arises due to the fact that the intended application of a microfluidic chip generally dictates its design. For instance, longer CE separation channels are required for sequencing of long nucleic acid sequences while smaller and more concise CE networks can be used to conduct multi-plexed enzyme assays. The result is that for different applications, the layout of fluidic network arrays from chip to chip will be different. Conventional analytical systems incorporate circuit (electrode) cards and voltage sources as fixtures. Accordingly, their versatility is limited, usually resulting in expensive systems dedicated to particular applications. For this reason, it is desired to have an analysis and detection system with the versatility to accommodate different chip designs in multiple configurations. Additionally, the chemical and biochemical reactions carried out in microfluidic chips are conducted using small quantities of sample and other fluids that easily evaporate. Therefore, a need also exists for a microfluidic analytical apparatus that alleviates evaporation of fluids within microfluidic chips.
- The above mentioned objects are achieved with a microfluidic analytical apparatus featuring a microfluidic chip having a configuration of ports in connection with channels and a circuit card having a surface with an array of conductive pin groups aligning with and corresponding to the microfluidic ports, with pins terminating in conductive pads disposed on another surface of the circuit card, the conductive pads aligning and being in electrical communication with conductive fingers providing voltages.
- In other words, the present invention pairs a microfluidic chip or card described above with a corresponding circuit card. The circuit card can be used repeatedly to provide voltages to microfluidic cards having the corresponding configuration in electrokinetic operations such as electrophoretic separation of analytes, the electrophoretic movement of molecules into or out of reaction chambers, isotachophoretic concentration of molecules, electroosmotic movement of fluidics through channels or chambers of the microfluidic card, or the like. The microfluidic card has a plurality of channels and ports on a top surface of the card, the ports in fluid communication with the channels. A multitude of configurations, including various numbers of channels and ports in various locations, are incorporated into different microfluidic cards. The circuit card has a plurality of conductive pins projecting from a bottom surface of the card and having a configuration that corresponds to a particular configuration of the ports of the microfluidic card with which it is paired.
- The circuit card is received within a holder that provides multiple functions. In one embodiment, the holder acts as a stop, which results in the suspension of the pins within the corresponding ports when the circuit card is paired with the microfluidic card. Therefore, the conductive pins of the circuit card contact the fluid within the ports or electrical circuits within the card ports, but not the ports themselves. Additionally, when the conductive pins of the circuit card are received within the ports, the holder contacts the microfluidic card and provides a seal between the microfluidic card and the circuit card thus assisting in preventing evaporation of material within the ports.
- An electrical connection between the microfluidic card and circuit card of the present invention is simple to form when the conductive pins, in electrical communication with a power source, are inserted within the corresponding ports. Conductive fingers connected to the power source provide voltages to the microfluidic card through the conductive pins of the circuit card. The pins of the circuit card are arranged in groups. The pins in each group are electrically connected through electrical traces to conductive pads that terminate on a top surface of the circuit card. The conductive pad configuration corresponds to the configuration of the conductive fingers. The conductive fingers contact the conductive pads and provide voltages to the pads, which travel to the traces and the conductive pins. When the conductive pins are received within the ports voltages are provided through the conductive fingers and various operations, including molecular separations of materials within the channels, can then take place.
- During sample separation detection mechanisms known in the art are used for sample analysis. Detection is usually optical and usually the signal is generated by laser-induced fluorescence; the detector can be a confocal optical system known in the art. Other detection mechanisms, such as electrochemical detection, may also be employed. In one embodiment of the invention, the detection mechanism such as a microscope is disposed within a holder that moves vertically during analysis in relation to the microfluidic card so as to maintain a constant distance from the surface of the microfluidic card. In one embodiment the microscope has a compliantly mounted head that is in sliding contact with the microfluidic card during analysis. The compliantly mounted head moves vertically in response to any non-uniformities or warpage that the card may have without requiring refocusing of the detection optics, since a constant distance from the optics to the card is maintained. This embodiment is particularly useful when microfluidic cards are made of plastic, or contain plastic components, such as covers, or the like, that although having well defined and precise small-scale structural features such as channel widths, wall thicknesses, port diameters, and the like, are susceptable to warpage, bends, and other defects, from manufacturing processes, handling, sample preparation, loading, or the like.
- Support frames are provided for the circuit card and the microfluidic card. In one embodiment the support frames are adapted for movement of the cards in relation to the confocal microscope.
- Apparatus according to the invention assist in providing multiple microfluidic manipulations at high throughput rates to allow for continuous processing of high number of analyses at high rates of speed. The complexity of mass screening programs is reduced for example by the simple to use configuration of the conductive fingers with respect to the conductive pads and the configuration of the conductive pins with respect to the microfluidic parts, thereby eliminating many of the manipulation steps that are required in the use of convention analytical apparatus.
- FIG. 1 is an exploded view of the apparatus of the present invention.
- FIG. 2 is a perspective view of the apparatus of the present invention pictured in FIG. 1 in conjunction with support frames.
- FIG. 3 is a perspective view of upper and lower frames of the apparatus of FIG. 2 supporting a microfluidic card and a circuit card.
- FIG. 4 is an exploded view of the circuit card and the microfluidic card of the present invention pictured in FIG. 1.
- FIG. 5 is a top view of a bottom surface of the circuit card of FIG. 4.
- FIG. 6 is a plan view of the microfluidic card of FIG. 4 and of a detection mechanism.
- With reference to FIGS. 1 and 2, there is seen an
embodiment 10 of the present invention featuring amicrofluidic card 12 paired with acircuit card 14 andconductive fingers 16 paired withconductive pads 18 of thecircuit card 14. Theconductive fingers 16 are electrically connected to and in electrical communication with a power source (not shown) and provide voltages to thecircuit card 14 during analysis of sample within themicrofluidic card 12. A detection system is employed for analysis of sample materials. In this embodiment of the invention, amicroscope 42 is used as a part of the detection system; however, various detection systems known in the art may be used. - A
holder 20 havingwings circuit card 14.Wing 26 can be used to grip theholder 20. Theholder 20 is made from a rigid material such as for example, a rigid plastic. - With reference to FIGS. 2 and 3 it is seen that
wings circuit card 14 slide within partiallyenclosed channels upper support frame 38 and adistal end 25 slides within partially enclosedchannel 32 of the upper frame.Grip 26 is proximal to the user and can be used to insert the holder within the channels. -
Shelves 34 upon which themicrofluidic card 12 rests are also seen. Theshelves 34 are a part of alower support frame 36. Other ways of maintaining the microfluidic card in place include clips, channels, grooves, adhesives, vacuums and differential pressure. - When a downward force is applied to the
upper frame 38 theholder 20 and thecircuit card 14 held by the holder move in a downward direction so that thecircuit card 14 makes contact with and pairs withmicrofluidic card 12 as seen in FIG. 2 and as described with reference to FIG. 4 below. A securing device such as a pair ofclamps frames upper frame 38 and thus thecircuit card holder 20. Each clamp includes for example,upper plates upper frame 38,lower plates apertures fasteners upper frame 38 down uponlower frame 36. When theclamps 40 are released (for example the fastener is removed from the apertures) theupper frame 38 is moved back to an upward position away fromlower frame 36 as seen in FIG. 3. Alternatively, pneumatic, electromagnetic or electromechanical securing mechanisms, as well as other mechanisms known in the art, may be used in addition to or in replacement ofclamps 40. - Positioned beneath the
lower frame 36 is themicroscope 42 disposed within aholder 44 adjacent to the microfluidic card 12 (whencard 12 rests upon shelves 34) used for detecting migrated samples within thecard 12. The microscope includes alens 46, which is facing themicrofluidic chip 12. Themicroscope holder 44 is attached to anair cylinder 48, which provides vertical movement to themicroscope 42 through theholder 44. In one embodiment additional actuators provide lateral movement. Other mechanisms for providing responsive vertical movement of the microscope optical head or lens known in the art may be used, such as springs or similar mechanical devices, electromagnetic suspension of the type used in optical readers of compact disc players, and the like. - With reference to FIG. 4 there is seen the
microfluidic card 12 used in conjunction with the present invention having an upper first opposedmajor surface 50 and a lower second opposedmajor surface 52. Thecard 12 may include various configurations ofports 54 on thesurface 50 andchannels 56 withinsurfaces card 12 being used is non-flexible, therefore it is not used in conjunction with a rigid support. A portion of themicrochannels 56 is used as a detection site, to detect migrated samples. The channels comprising the detection site will generally have a depth of about 10 to 200 μm and a width ranging from about 1 to 500 μm. The channels may be parallel or in various arrays and configurations. Depending on the purpose of the chip and the pattern of the channels, whether the channels are straight, curved or tortuous, the chip may only be 1 or 2 cm long or 50 cm long, generally being from about 2 to 20 cm long. The width will vary with the number and pattern of channels, generally being at least about 1 cm, more usually at least about 2 cm and may be 50 cm wide. The chip has ports, usually reservoirs for materials such as sample, buffer and waste that are connected to the channels. Additional channels may be connected to the main channel for transferring samples and reagents, etc. to the main channel. - The
circuit card 14 has upper and lower opposed major surfaces. With reference to FIGS. 4 and 5 a lower second opposedmajor surface 58 of thecircuit card 14 will now be described. A phantom view of the lower second opposedmajor surface 58 of thecircuit card 14 is seen in FIG. 4 and a top plan view of the second opposedmajor surface 58 is seen in FIG. 5. FIGS. 4 and 5 show an array ofconductive pins 60 protruding from the secondmajor surface 58. Thepins 60 have a configuration that corresponds to a particular configuration of theports 54 of the particularmicrofluidic card 12 that it is paired with. For instance, in this example the array ofpins 60 has the same configuration as theports 54 pictured on the microfluidic card 12 (FIG. 4) and the number ofpins 60 is equal to the number ofports 54. The conductive pins 60 are fine wires used as electrodes mounted on theunderside 58 ofcircuit card 14. The wires are usually platinum or other material with good electrical conductivity, substantially nonreactive (for example, platinum and gold) and corrosion resistant. having a diameter of for example, 200 to 500 micrometers. The pins may be rigid or compliant. For example, they may be spring-loaded or accordion-like. The electrode pins 60 act as cathodes and anodes for the separation of sample within thechannels 50 and provide other voltages to themicrofluidic card 12 for various operations. Electrode pins 60 may form wet or dry contacts withmicrofluidic card 12. - With reference to FIGS. 1 and 2 the upper surface of
circuit card 14 is seen. First opposedmajor surface 62 ofcircuit card 14 has a plurality ofconductive traces 64 that are connected to the array ofconductive pins 60 on the secondmajor surface 58.Traces 64 terminate inconductive pads 18 on thetop surface 62 electrically connected toconductive pins 60. - The conductive pins60 are arranged in groups of pins on the second major opposed
surface 58 wherein a particular group of pins is electrically connected to the sameconductive pad 18 throughtraces 64.Traces 64 may be present on either the first or second opposedmajor surfaces conductive pads 18 are electrically connected to an electrical power source (not shown) through conductive fingers 16 (FIG. 1). The power source is provided with controls to change the voltages at theconductive fingers 16 thus at theconductive pads 18 in physical contact with thefingers 16 and to theconductive pins 60 in electrical contact with thepads 18. The voltages are provided in a pattern determined according to the sequence of electroflow manipulations to be carried out in the microfluidic card during analysis.Conductive fingers 16 are made from any material with good electrical conductivity.Conductive fingers 16 extend from apertures (not shown) withinblock 66 and are connected to a power source at one end throughelectrical wiring 68 extending fromblock 66.Wiring 68 provides voltages to theconductive fingers 16. - The
conductive fingers 16 are arranged in a configuration that corresponds to the configuration ofconductive pads 18 found on the firstmajor surface 62 ofcircuit card 14. In FIGS. 1-3 eightconductive fingers 16 are seen arranged incolumns 70 of twofingers 16. Three of thecolumns 70 are grouped together and aspace 78 separates them from a fourth column.Conductive pads 18 oncircuit card 14 are arranged in the same configuration as theconductive fingers 16. Specifically, thepads 18 are arranged in groups of three columns close together and a fourth column spaced apart. In the example pictured there are moreconductive pads 18 thanconductive fingers 16. However, in another embodiment the same number of conductive pads as conductive fingers is present. Arranging theconductive pads 18 in the same configuration as theconductive fingers 16 provides that an electrical connection betweenconductive pads 18 and conductive fingers 7 . . . 6 is easily established as theconductive fingers 16 pair with theconductive pads 18. Theconductive fingers 16 move horizontally along thetop surface 62 of thecircuit card 14 and move vertically to align and make contact withconductive pads 18. As the conductive fingers are moved along to make contact withpads 18 various groupings ofpads 18 are provided with voltages. These voltages are provided topins 60 andports 54 of themicrofluidic card 12 so that sample analysis may occur. - With reference to FIGS. 2-3,
lower frame 36 andupper frame 38, in one embodiment, can move in a lateral or vertical position along tracks (not shown) to properly position themicrofluidic card 12 andcircuit card 14 for analysis by themicroscope 42. - Referring back to FIG. 4, the
conductive pins 60 are removably insertable within theports 54 of themicrofluidic chip 12. As stated above with regard to FIGS. 2 and 3 clamps 40 and 41, attached to theframes upper frame 38 supporting thecircuit card holder 20. Theholder 20 rests againstcard 12 and theconductive pins 60 enter and are suspended within theports 54. In one embodiment, edges 80 of theholder 20 act as stops that prevent theconductive pins 60 from contacting a bottom surface ofports 54. - Additionally, the
clamps holder 20 against thecard 12 forming a seal over the card. Fluids are sealed in theports 54 andchannels 56 when this seal is formed inhibiting evaporation of the fluids contained within the ports and channels. - There are many possible configurations and numbers of
ports 54 andchannels 56 that can be present onmicrofluidic cards 12 and corresponding configurations and numbers of theconductive pins 60 that are present on thecircuit card 14 dependent on the type of desired analysis. By manufacturing acircuit card 14 that hasconductive pads 18 that are configured as theconductive fingers 16 are, it is easy to establish electrical connections to theconductive pads 18 and to the electrically connectedconductive pins 60 thus providing voltages to theports 54 andchannels 56 of themicrofluidic device 12 for a desired operation. Regardless of the configuration ofports 54 andchannels 56 and correspondingconductive pins 60, the configuration of theconductive pads 18 remains constant. Theconductive pads 18 are configured to correspond to the arrangement of theconductive fingers 16. Therefore, theconductive finger 16 configuration will not have to be altered before analysis takes place, increasing the efficiency of the analysis. Additionally, various types ofmicrofluidic cards 12 andcorresponding circuit cards 14 can be produced, and yet eachcard 12, regardless of the configuration, can be easily interchangeable for use with theapparatus 10. - When the
conductive pins 60 are suspended within theports 54 and are connected to the appropriate voltage sources throughconductive pads 18 andconductive fingers 16, samples from theports 54 can be moved from the ports into theseparation channels 56 using an electric field. The separation channels are loaded with an appropriate separation medium. The voltages are changed to then separate the samples by means of electrophoresis. During sample separation a detection region on themicrofluidic card 12 is scanned usingmicroscope 42 pictured in FIG. 1. - With reference to FIG. 6, it is seen that in one embodiment of the present invention, the
microscope 42 has a compliantly mountedoptical head 82 withinholder 44. Thehead 82 includes at least one of the optical elements described below. The compliant mounting mechanism used to mount thehead 82 can be any mechanism that provides a vertical movement to the head that is responsive to deformities, such as warpage, or other irregularities, in the surface ofmicrofluidic card 12. Preferably, the head is rigidly mounted in every direction except the vertical direction, i.e. the head is rigidly mounted in directions parallel to the surface ofmicrofluidic card 12. “Rigidly mounted” means that the xy-position above (or below) the surface ofmicrofluidic card 12 is controlled by a user, e.g. through conventional position controller under computer program control, or the like. A wide variety of methods may be used to provide a compliant mounting for the lens that allows the lens to move vertically relative to the surface of the microfluidic card in response to deformities. Such methods include using a spacer mounted with the lens together with a forcing means for applying a force perpendicular to the surface of the microfluidic card onto the lens so that the spacer is held in slidable contact with the surface of the microfluidic card. Preferably, the spacer is a cylindrical spacer coaxially mounted with the lens so that optical signals emanating from a channel in the microfluidic card can be collected by the lens. Forcing means include springs, electromagnetic force, hydraulic force, such as compressed air, elastomeric materials, or the like. The head may move vertically through the use of, for example,air cylinder 48.Air cylinder 48 is connected through a mechanical connection, for example, pushrod 90 to head 82. Theair cylinder 48 provides vertical movement of theholder 44 along surfaces of themicrofluidic card 12 includingdeformities 84.Deformities 84 include non-planar or warped surfaces.Roller bearings 86 rigidly mount thehead 82 in the lateral direction and prevent the head from pivoting with theholder 44. Theair cylinder 48 moderates the force that is applied to thehead 82. The air cylinder is, for example, a soft air cylinder providing for example, 1-2 pounds of force that pushes a piston (not shown) of the cylinder upwardly and downwardly in a spring-like manner. Therefore, the moderate force that theair cylinder 48 provides helps to prevent damage to themicroscope head 82 and to thecard 12 when thehead 82 is moved vertically by theair cylinder 48 to contact thecard 12. As thehead 82 is compliantly mounted it is able to move within the holder and to make contact with thecard 12. In one example,nose piece 88 of thehead 82 is able to travel along in a sliding contact relation with a surface of themicrofluidic card 12, such as second opposedmajor surface 52 even when the card hasdeformities 84, without damaging thehead 82.Nose piece 88 rests against thesurface 52 of thecard 12 and in conjunction with theair cylinder 48 and compliant mechanism allowing for vertical movement maintainlens 46 at the correct distance from the channels within the card. Therefore, a significant attribute of themicroscope 42 is that it is able to track the samples withinchannels 56 throughwall 55 even though the channels and sample may be located within a card having non-uniform surfaces, without requiring refocusing of detection optics. Samples withinchannels 56 that otherwise could not be detected without manipulation of the detection optics or accurately detected with prior art mechanisms relying on a uniform shape of card can now be detected with ease. - In another embodiment,
optical head 82 ofmicroscope 42 may be rigidly mounted with collar, or nose piece, 88 andlens 46 compliantly mounted withinoptical head 82 so that they are responsive to deformities, warpage, or other irregularities in the surface ofmicrofluidic card 12. - Optical elements within
head 82 are elements known in the art used for sample detection. For example, these elements include anillumination beam 100 fromillumination source 102 that passes through alens 110, which serves to collect divergent light. Thebeam 100 is then reflected bydichroic mirror 112, which reflects light of the excitation wavelength of interest to pass through the mirror. The reflectedbeam 114 is focused bylens 46 and forms a small sharp beam, which passes into the detection regions ofchannels 56. Fluorophores within the channel will be excited and will emit light, which will exit the channel and be collected bylens 46. The emittedbeam 118 will pass throughdichroic mirror 112 and throughlens 120 which focuseslight beam 118 onphotodetector 122. The photodetector converts this light to electric signals for processing. The method by which themicroscope 42 uses the excitation beam to scan themicrofluidic card 12 can be a conventional confocal optical system known in the art or other detection mechanisms known in the art may be employed. The arrangement of optical elements described above may be substituted with other arrangements and types of optical elements used for sample detection.
Claims (30)
1. An interchangeable circuit card for providing electrical contact with one or more ports in a microfluidic chip, said card comprising:
first and second opposed major surfaces; one or more conductive pads disposed on said first surface;
one or more conductive pins projecting from said second surface, said one or more pins in electrical communication with said conductive pads whereby an electrical connection can be provided between a power source through said one or more pins to said one or more ports to effect an electrokinetic process.
2. The apparatus of claim 1 wherein said electrokinetic process includes separation by capillary electrophoresis.
3. The apparatus of claim 1 further comprising groups of pads on said first surface of said circuit card.
4. The apparatus of claim 3 further comprising traces wherein said traces connect groups of pins to one of said conductor pads and said traces terminate in said pads.
5. The apparatus of claim 3 further comprising conductive fingers in electrical communication with a power source and making electrical contact with said pads.
6. The apparatus of claim 5 wherein said conductive fingers align with a group of said pads.
7. The apparatus of claim 6 wherein the number of pads in said grouping is equal to the number of conductive fingers.
8. The apparatus of claim 1 further comprising a circuit cardholder having said circuit card disposed within it.
9. The apparatus of claim 8 wherein said circuit card holder having said circuit card disposed within it, rests against surfaces of said microfluidic card and covers said ports of said microfluidic card, decreasing evaporation of material within said ports.
10. The apparatus of claim 8 wherein said holder includes a stop and said stop prevents said conductive pin from contacting a port surface when received by said port.
11. The apparatus of claim 9 wherein said pins are suspended within said ports.
12. The apparatus of claim 8 wherein said apparatus further comprises an upper frame upon which said circuit card holder rests and a lower frame upon which said microfluidic card rests.
13. The apparatus of claim 12 wherein said holder has four sides and has wings extending from two sides, wherein said wings are insertable within said upper frame.
14. The apparatus of claim 8 further comprising a securing device wherein said securing device secures said microfluidic card into contact relation with said circuit card holder and said conductive pins are removably received by said ports.
15. The apparatus of claim 1 further comprising an optical head disposed in a holder adjacent to the second major surface of the card and in sliding contact relation with the second major surface of said card.
16. The apparatus of claim 1 further comprising a compliantly mounted optical head wherein said head is compliantly disposed within a holder and is adjacent to the second major surface of the card and in sliding contact relation with the second major surface.
17. The apparatus of claim 16 wherein said microfluidic card includes a non-uniform surface and said compliantly mounted optical head is in a sliding contact relation with said non-uniform surface.
18. A microfluidic analytical apparatus comprising:
a microfluidic card having,
(a) first and second opposed major surfaces,
(b) a plurality of microchannels formed between the major surfaces, each microchannel having ports extending to the first major surface of the microfluidic card, thereby forming an array of ports,
a circuit card in moveable proximity to the microfluidic card having,
(i) first and second opposed major surfaces,
(ii) an array of conductive pins projecting from said second surface and disposed adjacent to and projecting toward the first major surface of the card in a removably receivable relation with selected ports thereof, said array of pins corresponding to a select array of ports and said pins being arranged in groups,
(iii) conductive pads disposed on said first surface of said circuit card, a pad corresponding to and electronically connected to a group of pins, and
conductive fingers in electrical communication with a power source and making electrical contact with said pads, said fingers aligning with said pads.
19. The apparatus of claim 18 further comprising:
an optical head disposed in a holder adjacent to the second major surface of the card in sliding contact relation with the second major surface of said card.
20. The apparatus of claim 18 further comprising a circuit cardholder.
21. The apparatus of claim 20 wherein said holder includes a stop and said stop prevents said conductive pin from contacting a port surface when received by said port.
22. The apparatus of claim 18 wherein said microscope is beneath said microfluidic card and said fingers are above said microfluidic card.
23. A microfluidic analytical apparatus comprising: a microfluidic card having first and second opposed major surfaces, a plurality of microchannels formed between the major surfaces, each microchannel having ports extending to the first major surface of the microfluidic card, thereby forming an array of ports;
an optical head compliantly disposed in a holder, said head adjacent to the second major surface of the microfluidic card and in sliding contact relation with the second opposed major surface of said card.
24. The apparatus of claim 23 wherein said optical head includes a nose protruding from said head and said nose is in a sliding contact relation with the second major surface of said card.
25. The apparatus of claim 23 further comprising ball bearings wherein said bearings rigidly mount said head in a lateral direction within said holder.
26. The apparatus of claim 24 further comprising an air cylinder providing vertical movement to said head.
27. A microfluidic analytical apparatus comprising: a microfluidic card having first and second opposed major surfaces, a plurality of microchannels formed between the major surfaces, each microchannel having ports extending to the first major surface of the microfluidic card, thereby forming an array of ports;
a circuit. card in moveable proximity to the microfluidic card having first and second opposed major surfaces, an array of conductive pins projecting from said second surface and disposed adjacent to and projecting toward the first major surface of the card in a removably receivable relation with selected ports thereof; and
a circuit cardholder, wherein said circuit card is disposed within said holder and said holder rests against said microfluidic card when said card receives said conductive pin, thereby forming a seal between said circuit card and said microfluidic card.
28. The apparatus of claim 27 wherein said circuit cardholder includes a stop and said stop suspends said conductive pins within said ports.
29. An optical head for collecting optical signals from a microfluidic card, the optical head comprising:
a lens mounted in a holder capable of lateral movement with respect to a surface of a microfluidics card, the holder providing a compliant mounting with respect to the surface of the microfluidic card such that the lens undergoes vertical movement responsive to deformities in the surface of the microfluidics card, the vertical movement maintaining the lens at a constant vertical distance from the surface of the microfluidic card.
30. The optical head of claim 29 wherein said compliant mounting comprises a cylindrical spacer coaxially disposed between said lens and said surface of said microfluidic card, and forcing means for holding the cylindrical spacer in contact with said surface.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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US10/496,684 US20040257638A1 (en) | 2001-12-17 | 2002-12-06 | Microfluidic analytical apparatus |
US11/761,350 US7811523B2 (en) | 2001-12-17 | 2007-06-11 | Microfluidic analytical apparatus |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US34166401P | 2001-12-17 | 2001-12-17 | |
US10/496,684 US20040257638A1 (en) | 2001-12-17 | 2002-12-06 | Microfluidic analytical apparatus |
PCT/US2002/041651 WO2003052821A1 (en) | 2001-12-17 | 2002-12-06 | Microfluidic analytical apparatus |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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US11/761,350 Division US7811523B2 (en) | 2001-12-17 | 2007-06-11 | Microfluidic analytical apparatus |
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US20040257638A1 true US20040257638A1 (en) | 2004-12-23 |
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Family Applications (2)
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US11/761,350 Expired - Lifetime US7811523B2 (en) | 2001-12-17 | 2007-06-11 | Microfluidic analytical apparatus |
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US11/761,350 Expired - Lifetime US7811523B2 (en) | 2001-12-17 | 2007-06-11 | Microfluidic analytical apparatus |
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US (2) | US20040257638A1 (en) |
AU (1) | AU2002360822A1 (en) |
WO (1) | WO2003052821A1 (en) |
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DE102018218047A1 (en) * | 2018-10-22 | 2020-04-23 | Robert Bosch Gmbh | Shielding device for a chip laboratory analyzer, chip laboratory analyzer and method for operating a chip laboratory analyzer |
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US10214772B2 (en) | 2015-06-22 | 2019-02-26 | Fluxergy, Llc | Test card for assay and method of manufacturing same |
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CN108265003A (en) * | 2016-12-30 | 2018-07-10 | 广州康昕瑞基因健康科技有限公司 | Multichannel gene sequencing reaction cell and multichannel gene sequencing reaction device |
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Also Published As
Publication number | Publication date |
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US7811523B2 (en) | 2010-10-12 |
AU2002360822A1 (en) | 2003-06-30 |
WO2003052821A1 (en) | 2003-06-26 |
US20070264160A1 (en) | 2007-11-15 |
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