Devices and method for using centripetal acceleration to drive fluid movement in a microfluidics system with on-board informatics

Abstract

This invention relates to methods and apparatus for performing microanalytic and microsynthetic analyses and procedures. The invention provides a microsystem platform and a micromanipulation device for manipulating the platform that utilizes the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels. The microsystem platforms of the invention are also provided having system informatics and data acquisition, analysis and storage and retrieval informatics encoded on the surface of the disk opposite to the surface containing the fluidic components. Methods specific for the apparatus of the invention for performing any of a wide variety of microanalytical or microsynthetic processes are provided.

What is claimed is:  
     
         1 . A centripetally-motivated fluid micromanipulation apparatus that is a combination of 
 a microsystem platform, comprising a substrate having a first flat, planar surface and a second flat, planar surface opposite thereto, wherein the first surface comprises a multiplicity of microchannels embedded therein and a sample input means, wherein the sample input means and the microchannels are connected and in fluidic contact, and wherein the second flat, planar surface opposite to the first flat planar surface of the platform is encoded with an eletromagnetically-readable instruction set for controlling rotational speed, duration, or direction of the platform, and    a micromanipulation device, comprising a base, a rotating means, a power supply and user interface and operations controlling means, wherein the rotating means is operatively linked to the microsystem platform and in rotational contact therewith    wherein a volume of a fluid within the microchannels of the platform is moved through said microchannels by centripetal force arising from rotational motion of the platform for a time and a rotational velocity sufficient to move the fluid through the microchannels.    
     
     
         2 . A centripetally-motivated fluid micromanipulation apparatus that is a combination of 
 a microsystem platform, comprising a substrate having a first flat, planar surface and a second flat, planar surface opposite thereto, wherein the first surface comprises a multiplicity of microchannels, a reaction chamber and a reagent reservoir embedded therein, and a sample input means, wherein the sample input means, the microchannels, the reaction chamber and the reagent reservoir are connected and in fluidic contact, and wherein the second flat, planar surface opposite to the first flat planar surface of the platform is encoded with an eletromagnetically-readable instruction set for controlling rotational speed, duration, or direction of the platform, and    a micromanipulation device, comprising a base, a rotating means, a power supply and user interface and operations controlling means, wherein the rotating means is operatively linked to the microsystem platform and in rotational contact therewith    wherein a volume of a fluid within the microchannels of the platform is moved through said microchannels by centripetal force arising from rotational motion of the platform for a time and a rotational velocity sufficient to move the fluid through the microchannels.    
     
     
         3 . A centripetally-motivated fluid micromanipulation apparatus that is a combination of 
 a microsystem platform, comprising a substrate having a first flat, planar surface and a second flat, planar surface opposite thereto, wherein the first surface comprises a multiplicity of microchannels, a reaction chamber and a reagent reservoir embedded therein and a sample input means, wherein the sample input means, the microchannels, the reaction chamber and the reagent reservoir are connected and in fluidic contact, and wherein fluid motion from the microchannels, the reaction chamber and the reagent reservoir is controlled by microvalves connected thereto, and wherein the second flat, planar surface opposite to the first flat planar surface of the platform is encoded with an eletromagnetically-readable instruction set for controlling rotational speed, duration, or direction of the platform, and    a micromanipulation device, comprising a base, a rotating means, a power supply and user interface and operations controlling means, wherein the rotating means is operatively linked to the microsystem platform and in rotational contact therewith    wherein a volume of a fluid within the microchannels of the platform is moved through said microchannels by centripetal force arising from rotational motion of the platform for a time and a rotational velocity sufficient to move the fluid through the microchannels.    
     
     
         4 . The apparatus of    claim 1   , wherein the first flat, planar surface and second flat, planar surface of the microsystem platform form a disk.  
     
     
         5 . The apparatus of    claim 1   , wherein the first and second flat, planar surfaces of the microsystem platform define a centrally located aperture that is engaed to a spindle on the micromanipulation device, whereby rotational motion of the spindle is translated into rotational motion of the microsystem platform.  
     
     
         6 . The apparatus of    claim 1   , wherein the microsystem platform is constructed of an material selected from the group consisting of an organic material, an inorganic material, a crystalline material and an amorphous material.  
     
     
         7 . The apparatus of    claim 6   , wherein the microsystem platform is further comprises a material selected from the group consisting of silicon, silica, quartz, a ceramic, a metal or a plastic.  
     
     
         8 . The apparatus of    claim 4   , wherein the microsystem platform is a disk having a radius of about 1 to 25 cm.  
     
     
         9 . The apparatus of    claim 1   , wherein the microsystem platform has a thickness of about 0.1 to 100 mm, and wherein the cross-sectional dimension of the the microchannels between the first and second flat, planar surfaces is less than 500 μm and from 1 to 90 percent of said cross-sectional dimension of the platform.  
     
     
         10 . The apparatus of    claim 10   , wherein the microsystem platform has a thickness of about 0.1 to 100 mm, and wherein the cross-sectional dimension of the reaction chamber or the reagent reservoir between the first and second flat, planar surfaces is from 1 to 75 percent of said thickness of the platform.  
     
     
         11 . The apparatus of    claim 1   , wherein the microsystem platform is rotated at a rotational velocity of about 1 to about 30,000 rpm.  
     
     
         12 . The apparatus of    claim 1   , wherein the microsystem platform comprises a multiplicity of sample input means, reagent reservoirs, reaction chambers and microchannels connected thereto and embedded therein, wherein a volume of a fluid containing a sample is moved on the disk from the sample input means into and out from the reaction chambers, and a volume of a reagent is moved from the reagent reservoirs into and out from the reaction chambers, by centripetal force arising from rotation of the microsystem platform.  
     
     
         13 . The apparatus of    claim 1   , wherein the microsystem platform comprises a detecting chamber embedded within the first planar surface of the platform and connected to a microchannel, and wherein the micromanipulation device comprises a detecting means, whereby the detecting chamber is assayed by the detecting means to yield an assay output.  
     
     
         14 . The apparatus of    claim 13   , wherein the detecting means on the device is brought into alignment with the detection chamber on the platform by rotational motion of the microsystem platform.  
     
     
         15 . The apparatus of    claim 13   , wherein the detecting means comprises a light source and a photodetector.  
     
     
         16 . The apparatus of    claim 15   , wherein the light source illuminates the detection chamber wherein light is reflected transversely through the detection chamber and detected by a photodetector.  
     
     
         17 . The apparatus of    claim 16   , wherein the detection chamber on the microsystem platform is optically transparent.  
     
     
         18 . The apparatus of    claim 14   , wherein the detecting means is stationary and samples the detection chamber at a frequency equal to the frequency of rotation of the platform or multiples thereof.  
     
     
         19 . The apparatus of    claim 18   , wherein the detecting means comprises a stroboscopic light source.  
     
     
         20 . The apparatus of    claim 19   , wherein the detecting means is a monochromatic light source.  
     
     
         21 . The apparatus of    claim 13   , wherein the detecting means detects absorbance, fluorescence, chemiluminescence, light-scattering or radioactivity.  
     
     
         22 . The apparatus of    claim 1   , further comprising a temperature controlling element in thermal contact with the microplatform.  
     
     
         23 . The apparatus of    claim 1    further comprising a thermal detecting unit in thermal contact with the microplatform.  
     
     
         24 . The apparatus of    claim 1   , wherein the microsystem platform comprises a filtering means linked to a microchannel.  
     
     
         25 . The apparatus of    claim 1   , wherein the microsystem platform comprises a mixing element connected to a reaction reservoir or a microchannel.  
     
     
         26 . The apparatus of    claim 25   , wherein the microsystem platform comprises a static mixer comprising a textured surface of a reaction reservoir or microchannel.  
     
     
         27 . The apparatus of    claim 3   , wherein the microsystem platform comprises a multiplicity of microvalves operatively linked to the microchannels, reaction reservoirs, reagent chambers, sample input means and sample outflow ports, wherein fluid flow on the microsystem platform is controlled by opening and closing the microvalves.  
     
     
         28 . The apparatus of    claim 27   , wherein the microsystem platform comprises a capillary microvalve connected to a reaction chamber or microchannel.  
     
     
         29 . The apparatus of    claim 1   , wherein the microsystem platform comprises a multiplicity of air channels, exhaust air ports and air displacement channels.  
     
     
         30 . The apparatus of    claim 1   , wherein the rotating means of the device is an electric motor.  
     
     
         31 . The apparatus of    claim 1   , wherein the device comprises a rotational motion controlling means for controlling the rotational acceleration and velocity of the microsystem platform.  
     
     
         32 . The apparatus of    claim 1   , wherein the device includes a user interface comprising a monitor and an alphanumeric keypad.  
     
     
         33 . The apparatus of    claim 1   , wherein the device comprises an alternating current or direct current power supply.  
     
     
         34 . The apparatus of    claim 1   , wherein the microsystem platform includes an electrical connector in contact with an electric connector connected to the micromanipulation device.  
     
     
         35 . The apparatus of    claim 1   , wherein the device comprises a microprocessor and a memory connected thereto.  
     
     
         36 . The apparatus of    claim 1   , wherein the device comprises a reading or writing means.  
     
     
         37 . The apparatus of    claim 36   , wherein the reading means is a compact disk laser reading means.  
     
     
         38 . The apparatus of    claim 36   , wherein the writing means is a compact disk writing means.  
     
     
         39 . The apparatus of    claim 1   , wherein the second flat, planar surface of the microsystem platform is encoded with machine language instructions.  
     
     
         40 . The apparatus of    claim 39   , wherein the machine language instructions control operation of the platform, data acquisition or analysis from the platform, data storage and retrieval, communication to other devices, or direct apparatus performance diagnostics.  
     
     
         41 . The apparatus of    claim 1   , wherein the micromanipulation device includes a read-only memory or permanent storage memory that is encoded with machine language instructions.  
     
     
         42 . The apparatus of    claim 41   , wherein the machine language instructions control operation of the platform, data acquisition or analysis from the platform, data storage and retrieval, communication to other devices, or direct apparatus performance diagnostics.  
     
     
         43 . The apparatus of    claim 1    further comprising first and second microsystem platforms in contact with one another across one planar surface of each microsystem platform.  
     
     
         44 . The apparatus of    claim 1   , wherein the microsystem platform is rotated at a velocity of from about 1 to about 30,000 rpm.  
     
     
         45 . The apparatus of    claim 1   , wherein fluid on the microsystem platform is moved within the microchannels of the platform with a fluid velocity of from about O.lcm/sec to about 1000 cm/sec.  
     
     
         46 . An apparatus according to    claim 1    for measuring the amount of an analyte in a biological sample, wherein the microsystem platform comprises 
 a multiplicity of sample inlet ports, arranged concentrically around the center of the platform, wherein each of the sample inlet ports is operatively linked to  
 a multiplicity of microchannels arrayed radially away from the center of the platform, said microchannels being operatively linked to  
 a multiplicity of reagent reservoirs containing a reagent specific for the analyte to be measured, wherein release of the reagent from each of the reservoirs is controlled by a microvalve, and wherein the multiplicity of microchannels is also operatively linked to  
 a multiplicity of analyte detection chambers arranged peripherally around the outer edge of the microplatform,  
 wherein movement of the biological sample from the sample inlet port and through the microchannel, and movement of the reagent from the reagent reservoir and through the microchannel, is motivated by centripetal force generated by rotational motion of the microsystem platform.  
 
     
     
         47 . The apparatus of    claim 46    wherein the biological sample is blood, urine, cerebrospinal fluid, plasma, saliva, semen, or amniotic fluid.  
     
     
         48 . The apparatus of    claim 46    wherein the analyte detection chambers are opticallytransparent.  
     
     
         49 . The apparatus of    claim 46    further comprising electrical wiring between each of the microvalves and an electrical controller unit, wherein valve opening and closing is controlled by electrical signals from the controller unit.  
     
     
         50 . The apparatus of    claim 46    wherein the microchannels are arrayed linearly from the center of the platform to the periphery.  
     
     
         51 . The apparatus of    claim 46    wherein the mirochannels are arrayed concentrically from the center of the platform to the periphery.  
     
     
         52 . The apparatus of    claim 46    wherein the micromanipulation device comprises a detecting means.  
     
     
         53 . The apparatus of    claim 46    wherein the detecting means is stationary and samples the analyte detection chamber output at a frequency equal to the frequency of rotation of the platform or multiples thereof.  
     
     
         54 . The apparatus of    claim 46    wherein the detecting means comprises a stroboscopic light source.  
     
     
         55 . The apparatus of    claim 46   , wherein the detecting means is a monochromatic light source.  
     
     
         56 . The apparatus of    claim 46   , wherein the detecting means detects fluorescence, chemiluminescence, light-scattering or radioactivity.  
     
     
         57 . A method for measuring the amount of an analyte in a biological sample, the method comprising the steps of 
 applying the biological sample to a sample inlet port of the Microsystems platform of    claim 46   ,    placing the Microsystems platform in a micromanipulation device,    providing rotational motion to the Microsystems platform for a time and at a velocity sufficient to motivate the biological sample containing the analyte from the sample inlet port through the microchannel,    opening each of the microvalves controlling release of the reagent from the reagent reservoirs by generating a signal from the controlling unit, at a time and for a duration whereby the reagent moves into the microchannel and is mixed with the biological sample,    observing the mixture of the biological sample and the reagent in the analyte detection chamber, whereby a detector comprising the device detects a signal proportional to the amount of the analyte present in the biological sample, and    recording the measurement of the amount of the analyte in the biological sample.    
     
     
         58 . The method of    claim 57   , wherein the biological sample is blood, urine, cerebrospinal fluid, plasma, saliva, semen, or amniotic fluid.  
     
     
         59 . The method of    claim 57   , wherein the measurment of the amount of analyte in the sample is recorded in the device, on the microplatform, or both.  
     
     
         60 . The method of    claim 57   , wherein the analyte detection chamber on the microsystem platform is optically transparent.  
     
     
         61 . The method of    claim 57   , wherein the signal detected is the analyte detection chamber is detected at a frequency equal to the frequency of rotation of the platform ot multiplesd thereof.  
     
     
         62 . The method of    claim 57   , wherein the signal detected is a monochromatic light signal.  
     
     
         63 . The method of    claim 62   , wherein the signal detected is a fluorescence signal, a chemiluminescence signal or a calorimetric signal.  
     
     
         64 . An apparatus according to    claim 1    for detecting gas or particles comprising an environmental sample, wherein the microsystem platform comprises 
 a multiplicity of sample inlet ports, arranged concentrically around the center of the platform, wherein the sample ports comprise an air intake vent and connecting funnel channel, wherein each of the sample inlet ports is operatively linked to  
 a multiplicity of microchannels arrayed radially away from the center of the platform, said microchannels being operatively linked to  
 a multiplicity of reagent reservoirs containing a reagent specific for the gas or particles to be detected, wherein release of the reagent from each of the reservoirs is controlled by a microvalve, wherein the microvalves are in electrical contact with a controller unit, and wherein the multiplicity of microchannels is also operatively linked to  
 a multiplicity of gas or particle detectors arranged peripherally around the outer edge of the microplatform,  
 wherein movement of the environmental sample from the sample inlet port and through the microchannel, and movement of the reagent from the reagent reservoir and through the microchannel, is motivated by centripetal force generated by rotational motion of the microsystem platform.  
 
     
     
         65 . The apparatus of    claim 64   , wherein the environmental sample comprises air, water, soil, or disrupted biological matter.  
     
     
         66 . The apparatus of    claim 64   , wherein the detector comprises a gas sensor chip.  
     
     
         67 . The apparatus of    claim 64   , wherein the detector comprises an optically-transparent particle collection chamber.  
     
     
         68 . The apparatus of    claim 67   , wherein the detector also comprises a coherent light source.  
     
     
         69 . The apparatus of    claim 68   , wherein the particles are detected by light scattering.  
     
     
         70 . The apparatus of    claim 64   , wherein the detector comprises a particle collection chamber operatively connected by a microchannel to a reagent reservoir comprising a reagent for chemically testing the particles.  
     
     
         71 . A method for detecting gas or particles comprising an environmental sample, wherein the method comprises the steps of 
 contacting the environmental sample with a sample inlet port of the microsystems platform of    claim 64   ,    placing the Microsystems platform in a micromanipulation device,    providing rotational motion to the Microsystems platform for a time and at a velocity sufficient to motivate the gaseous or pariculate environmental sample from the sample inlet port through the microchannel,    opening each of the microvalves controlling release of the reagent from the reagent reservoirs by generating a signal from the controlling unit, at a time and for a duration whereby the reagent moves into the microchannel and is mixed with the environmental sample,    detecting the mixture of the environmental sample and the reagent or the gaseous or particulate component of the environmental sample directly in the gas or particle detection chamber, whereby the detector detects a signal proportional to the amount of the gas or particulate present in the environmental sample, and    recording the measurement of the amount of the gas or particulate in the environmental sample.    
     
     
         72 . The method of    claim 71   , wherein the environmental sample comprises air, water, soil, or disrupted biological matter.  
     
     
         73 . The method of    claim 71   , wherein a gas is detected by a gas sensor chip.  
     
     
         74 . The method of    claim 71   , wherein a particle is detected in an optically-transparent particle collection chamber.  
     
     
         75 . The method of    claim 71   , wherein the particle is detected by coherent light scattering.  
     
     
         76 . The method of    claim 71   , wherein a particle is detected in a particle collection chamber operatively connected by a microchannel to a reagent reservoir comprising a reagent for chemically testing the particles, wherein the particulate is mixed and reacted with the reagent in the microchannel after release of the reagent by activation of a micvrovalve and rotation of the platform.  
     
     
         77 . An apparatus according to    claim 1   , wherein the microsystem platform is comprised of a stacked layer of thin film disks comprising microchannels, sample inlet ports, reactant reservoirs, reaction chambers and sample outlet ports, wherein each of the stacked film disks is self-contained and provides a platform of the invention.  
     
     
         78 . An apparatus of    claim 1    for determining a hematocrit value from a blood sample, wherein the microsystem platform is comprised of a radial array of microchannels having a diameter of about 100 μm wherein the microchannels are treated with heparin to prevent coagulation, and wherein the microchannels are open at one end proximal to the center of ths disk, the apparatus also comprising a coherent light source and a recording means operatively connected thereto comprising the micromanipulation device, and wherein movement of the blood sample through the microchannel is motivated by centripetal force generated by rotational motion of the microsystem platform.  
     
     
         79 . An apparatus of    claim 78   , wherein the coherent light source is mounted on a movable track arrayed radially from the center of rotation of the platform.  
     
     
         80 . An apparatus of    claim 78    further comprising a Clarke electrode operatively connected to each of the microchannels of the microsystem platform, wherein the electrode is in contact with a blood sample within the microchannel.  
     
     
         81 . An apparatus of    claim 78    further comprising a Severing electrode operatively connected to each of the microchannels of the microsystem platform, wherein the electrode is in contact with a blood sample within the microchannel.  
     
     
         82 . A method for determining a hematocrit value from a blood sample, the method comprising the steps of 
 applying the blood sample to the proximal end of a microchannel of the Microsystems platform of    claim 78   ,    placing the Microsystems platform in a micromanipulation device,    providing rotational motion to the Microsystems platform for a time and at a velocity sufficient to motivate the red blood cells comprising the blood sample to move along the extent of the microchannel,    scanning the microchannel along its length with the coherent light source,    detecting a change in light scatter at a position along the microchannel that defines a boundary between the red blood cells and blood plasma,    recording the position of the boundary for each microchannel, and    comparing the position of this boundary for each microchannel with a standard curve relating hematocrit values to the position of the boundary, and recording the hematocrit determined thereby.    
     
     
         83 . A method for determining a blood oxygenation value from a blood sample, the method comprising the steps of 
 applying the blood sample to the proximal end of a microchannel of the Microsystems platform of    claim 80   ,    placing the Microsystems platform in a micromanipulation device,    providing rotational motion to the Microsystems platform for a time and at a velocity sufficient to motivate the blood sample to come in contact with the Clarke electrode connected to the microchannel,    detecting a blood oxygenation value for he blood sample, and    recording the blood oxygenation value determined thereby.    
     
     
         84 . An apparatus of    claim 1   , wherein the microsystem platform comprises a multiplicity of sample input means, reactant reservoirs, reaction chambers, microvalves and microchannels operatively connected thereto and embedded therein, wherein the microsystem platform is comprised of a stacked array of layers wherein a first layer comprises the sample input means, reactant reservoirs, reaction chambers and microchannels, a second layer comprises the microvalves, a third layer comprises electrical connections from the microvalves to an electrical controller unit, and the fourth layer comprises a sealing layer, wherein the layers are stacked on top of the solid substrate of the Microsystems platform and fused thereto.