Abstract:
The invention is directed to a method and device for routing, mixing, or reacting droplets or liquid microstreams along the surface of a flat substrate. The flow of liquid microstreams or microdroplets along designated pathways is confined by chemical surface patterning. Individually addressable heating elements, which are embedded in the substrate, can be used to generate flow via thermocapillary effects or to trigger or quench chemical reactions. The open architecture allows the liquid to remain in constant contact with the ambient atmosphere. The device can be used for microfluidic applications or as a surface reactor or biosensor, among other applications.

Description:
[0001]    This application claims priority of U.S. Provisional Application Serial No. 60/245,119 filed Nov. 2, 2000, U.S. Provisional Application Serial No. 60/248,860 filed Nov. 9, 2000 and U.S. Provisional Application Serial No. 60/248,861 filed Nov. 9, 2000 which are hereby incorporated by reference. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    The present invention relates to control of liquid flows on a microfluidic chip and in particular to routing, reacting and mixing liquid microstructures on the surface of a rigid or flexible substrate using a combination of one or more of the following: high resolution temperature control at individual addressable electronic elements for generating thermocapillary flow of the liquid; surface patterning for confining the liquid at one or more particular locations on the chip; obtaining heterogeneous surfaces with hydrophilic and hydrophobic regions; and retaining hydrophilicity of surfaces.  
           [0004]    2. Description of the Related Art  
           [0005]    Technological developments in the miniaturization and integration of multiple functionalities for chemical analysis and synthesis into a hand held device have generated interest in developing efficient methods for transporting ultra small volumes of liquid through networked arrays. Conventional techniques include micromechanical and electric field driven methods for manipulating and controlling flow including pneumatic actuation, electro-osmotic, electrophoretic or electrowetting techniques, centrifugation and magnetic field driven pumping.  
           [0006]    U.S. Pat. No. 6,124,138 describes a device for detecting or quantitating one or more of a plurality of different analytes in a liquid sample. The device includes a sample distribution network having a sample inlet, one or more detection chambers and a dead end fluid connection between the chambers and the inlet. A liquid sample is applied to the sample inlet and is drawn by vacuum action to deliver the sample to the detection chambers. The delivered sample reacts with at least one analyte specific reagent in each detection chamber under conditions effective to produce a detectable signal. A temperature controller can be used to heat or cool the detection chambers to facilitate reaction of the sample with the analyte detection reagents.  
           [0007]    U.S. Pat. No. 6,306,273 describes a method for transporting a liquid in a channel of a microfluidic system by electrokinetic action in which a liquid containing material comprises a plurality of charged chemical species. A voltage is applied from one point along the channel to a different point along the channel whereby the charged chemical species are transported along the channel. Fields in the range of 200-600 V/cm are typically used to control the electro-osmotic flow.  
           [0008]    One developed thermally based device uses thermocapillary pumping for pushing discrete liquid droplets through an enclosed microfabricated channel, as described in T. S. Sammarco and M. A. Burns, Thermocapillary Pumping of Discrete Drops in Microfabricated analysis devices [AIChE Journal45:350-366 (1999)]. This device allows discrete liquid plugs to advance through an interior channel by locally heating or cooling one of the droplet endcaps which induces a differential in capillary pressure. Micromechanical devices have the limitation that moving parts, such as miniature pumps and gears, often suffer leakage and degradation under wear. Electrokinetic and pneumatic techniques have the limitation that because the flow is confined to interior channels, particulates and aggregates in solution can block flow and destroy pumping action. Electrically based methods typically require external supply voltages of several kV. Each of the above-described devices also has the limitation of being capable of handling either continuous streams or discrete droplets but not both due to the flow mechanism on which they are based.  
           [0009]    The mixing of liquids in microscale devices is often difficult to attain due to the absence of turbulent phenomena. Many devices therefore rely on the action of diffusion and laminar flow. It is therefore desirable to provide a method and system for routing, reacting and mixing small volumes of liquid on the surface of a substrate, without the need for moving parts, high pressure or vacuum. It would also be advantageous to operate such devices using low voltages which are compatible with conventional integrated circuits.  
         SUMMARY OF THE INVENTION  
         [0010]    The invention is directed to a method and device for routing, mixing, or reacting droplets or liquid microstreams along the surface of a flat substrate. The flow of liquid microstreams or microdroplets along designated pathways is confined by chemical surface patterning. Individually addressable heating elements, which are embedded in the substrate, can be used to generate flow via thermocapillary effects or to trigger or quench chemical reactions. The open architecture allows the liquid to remain in constant contact with the ambient atmosphere. The device can be used for microfluidic applications or as a surface reactor or biosensor, among other applications.  
           [0011]    Thermocapillary actuation is based on the surface stress created by variations in surface tension at a gas-liquid or liquid-liquid interface. Variations in surface tension are created by temperature differences along such interfaces which can be directly applied by contacting the liquid to a differentially heated surface. For sufficiently thin liquid films in which the overlying fluid is a gas, the thermal map applied to the substrate is reproduced at the gas-liquid interface.  
           [0012]    In an embodiment of the present invention, a liquid is received on a patterned surface comprising one or more pathways. The patterned surface can be formed of one or more hydrophobic regions confining a hydrophilic surface in which the liquid flows along the hydrophilic surface. One or more of a plurality of heating elements are in registry with the patterned surface. The heating elements are individually activated under conditions effective for routing the fluid on the patterned surface. The activated heating elements form a thermal map. In an embodiment of the present invention, activation of the thermal map divides a liquid stream into one or more droplets. In another embodiment, activation of the thermal map initiates or quenches a reaction. In another embodiment, activation of the thermal map effects mixing of two or more streams or two or more droplets. Alternatively, activation of the thermal map traps or releases one or more droplets.  
           [0013]    In one aspect of the present invention, an airborne material is absorbed in liquid received on the device. The airborne material is detected in the liquid. In a further aspect, a method is described for fabrication of the device. In another aspect, a method is described for forming refreshable hydrophobic and hydrophilic surfaces. The refreshable surfaces can be used with the device of the present invention. In another aspect a method is provided for storing the device.  
           [0014]    The invention will he more fully described by reference to the detailed description when read in light of the following drawings. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0015]    [0015]FIG. 1 is a cross section of one embodiment of the thermal fluidic device in accordance with the teachings of the present invention.  
         [0016]    [0016]FIG. 2 is a schematic diagram of an embodiment of an arrangement of heating elements in an active-matrix array including an electronic addressing scheme.  
         [0017]    [0017]FIG. 3 is a schematic diagram of one embodiment of a heater cell in an active-matrix array.  
         [0018]    [0018]FIG. 4 a  is a diagram of an electronically controlled thermal map for providing flow of a continuous stream of fluid by application of a linearly decreasing temperature profile.  
         [0019]    [0019]FIG. 4 b  is a diagram of an electronically controlled thermal map for dividing a continuous stream of liquid into droplets by application of a zig-zag shaped temperature profile.  
         [0020]    [0020]FIG. 4 c  is a diagram of an electronically controlled thermal map for droplet isolation and trapping and subsequent heating or cooling.  
         [0021]    [0021]FIG. 4 d  is a diagram of an electronically controlled thermal map for moving a previously trapped droplet.  
         [0022]    [0022]FIG. 5 is a plan view of a possible network of hydrophilic surface pathways.  
         [0023]    [0023]FIG. 6 a  is a schematic diagram of an initial conformation of two liquids to be mixed which are supported on a differentially heated substrate.  
         [0024]    [0024]FIG. 6 b  is a schematic diagram of thermocapillary driven mixing of two fluids enforced by an electronically controlled differentially heated substrate.  
         [0025]    [0025]FIG. 7 a  is a schematic diagram of a square shaped hydrophilic reservoir.  
         [0026]    [0026]FIG. 7 b  is a schematic diagram of a circular shaped hydrophilic reservoir.  
         [0027]    [0027]FIG. 7 c  is a schematic diagram of a diamond shaped hydrophilic reservoir.  
         [0028]    [0028]FIG. 8 a  is a schematic diagram of a network comprising a linear pathway connecting a source and target reservoir.  
         [0029]    [0029]FIG. 8 b  is a schematic diagram of a network of a plurality of linear pathways connecting a source and target reservoir.  
         [0030]    [0030]FIG. 8 c  is a schematic diagram of a sinuous pathway connecting a source and target reservoir.  
         [0031]    [0031]FIG. 9 a  is a schematic diagram of a network including a plurality of vertical pathways having a plurality of reservoirs interconnected to a horizontal pathway.  
         [0032]    [0032]FIG. 9 b  is a schematic diagram of a network comprising rectilinear intersecting pathways.  
         [0033]    [0033]FIG. 9 c  is a schematic diagram of a network comprising a radial arrangement of pathways.  
         [0034]    [0034]FIG. 9 d  is a schematic diagram of a network including a plurality of vertical pathways intersecting a horizontal pathway.  
         [0035]    [0035]FIG. 9 e  is a schematic diagram of a plurality of horizontal pathways connected by an intersecting sinuous pathway.  
         [0036]    [0036]FIG. 10 is a schematic diagram of various dispensing geometries for introducing fluid onto hydrophilic pathways.  
         [0037]    [0037]FIG. 1 a  is a plan view of one embodiment of the thermal fluidic device as a gas sensor or biosensor.  
         [0038]    [0038]FIG. 11 b  is a bottom view of one embodiment of the thermal fluidic device as a gas sensor or biosensor.  
         [0039]    [0039]FIG. 12 is a flow diagram of an exemplary process for fabrication of the device.  
         [0040]    [0040]FIG. 13 is a flow diagram of a method for forming a refreshable hydrophobic surface pattern. 
     
    
     DETAILED DESCRIPTION  
       [0041]    The following terms and phrases as used herein are intended to have the meanings below. The term “surface pathways” refers to either a flat topology with chemical patterning or an indentation, ridge or groove optionally having chemical patterning. The term “hydrophilic pathways” refers to hydrophilic lanes surrounded by hydrophobic regions such that an appropriate liquid sample will remain confined to the hydrophilic portions. The hydrophilic pathways can be flush with the hydrophobic layer or include ridges or grooves.  
         [0042]    The term “hydrophilic” refers to a surface which is either completely or partially wetted by the liquid sample, in contrast to a hydrophobic surface on which the liquid assumes a contact angle exceeding ninety degrees. The contact angle is defined at the interior tangent angle of the air-liquid interface at the three phase boundary consisting of the gas, liquid and solid phases.  
         [0043]    Reference will now be made in greater detail to embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numerals will be used throughout the drawings and the description to refer to the same or like parts.  
         [0044]    [0044]FIG. 1 illustrates a cross-sectional view of an exemplary device  10  in accordance with the teachings of the present invention. Device  10  includes substrate  12 . Substrate  12  can be formed of any solid material whether rigid or flexible which is suitable for use in combination with components described below. Exemplary suitable materials for substrate  12  include various plastic polymers and copolymers, such as polypropylene, polystyrenes, polyimides and polycarbonates. Substrate  12  can also be formed of inorganic materials such as glass, metal or silicon. Substrate  12  can be formed from a single material or from a plurality of materials.  
         [0045]    Surface  11  of substrate  12  is coupled to heat sink  13 . Heat sink  13  can be formed of any heat transfer device capable of removing heat from device  10 . For example, heat sink  13  can be a Peltier cooler device or a metal block cooled by a steady internal flow of coolant.  
         [0046]    Passivation layer  9  can be optionally coupled to surface  15  of substrate  12  to provide a reproducible surface for subsequent processing steps or to improve the mechanical adhesion of subsequently deposited layers.  
         [0047]    Insulator layer  14  can be optionally coupled to surface  15  of substrate  12  or passivation layer  9 . Insulator layer  14  can be formed of a material suitable for providing thermal and/or electrical insulation. Alternatively, if substrate  12  is formed of a material with low thermal conductivity, insulator layer  14  is not required. Examples of suitable materials for insulator layer  14  include polyimides or other polymeric or organic materials, as well as organic or inorganic porous materials.  
         [0048]    A plurality of heating elements  16  are deposited onto insulator layer  14  or directly onto substrate  12 , if insulator layer  14  is not used. Planarization and electrical insulation layer  8  is deposited over heating elements  16  and exposed surfaces of insulation layer  14  or substrate  12 . Heating elements  16  are embedded in insulation layer  8 . Patterned surface layer  18  is in registry with heater elements  16 . Patterned surface layer  18  can include hydrophobic portions patterned on a hydrophilic layer. Optionally planarization aspect of layer  8  can be deposited on top of heater elements  16  if a flat surface topology is desired for subsequent processing or device operation. For cases in which the liquid being transported is volatile, the device can be encapsulated with an overlying glass or plastic containing surface  17  whose interior region may be saturated to reduce evaporation.  
         [0049]    Liquid microstructures contact the hydrophilic regions of patterned surface layer  19  as described in more detail below. Suitable liquids include, but are not limited to water, glycerol, tetra(ethylene glycol), polydimethylsiloxane, organic solvents, cell cultures, animal or human bodily fluids, solutions comprising suspended particles, solutions comprising biological molecules, cellular cytoplasm, cellular extracts, cellular suspensions, solutions of labeled particles or biological molecules, solutions comprising liposomes, encapsulated material, or micelles, etc. In another embodiment of the invention, the liquid can further contain solid particulates or other droplets, as in a liquid emulsion. By way of example, but not by way of limitation, particulates are any polymer particle, such as polystyrene particles or beads, metal colloids (e.g., gold colloidal particles), magnetic particles, dielectric particles, nanocrystals of materials, and bioparticles, such as spores, pollen, cellular oclusions, precipitates, intracellular crystals, etc. In possible embodiments of the invention, the particles are in the nanometer and/or micrometer size range, for example, but not limited to, from about 1 nm to about 100 μm.  
         [0050]    In still another embodiment of the invention, the liquid contains biological molecules, such as but not limited to, polynucleotides such as DNA and RNA, polysaccharides, polypeptides, proteins, lipids, and any other cellular components.  
         [0051]    In an embodiment of the invention, the liquid comprises viruses, such as but not limited to, viruses capable of infecting any organisms including microorganisms, plants or animals, in particular, mammals and especially humans. Further viruses in the categories of viruses with or without coat and viruses categorized as DNA or RNA viruses, either double stranded or single stranded are encompassed by the present invention.  
         [0052]    In yet another embodiment, liquid further comprises one or more biological cells which are capable of being routed, mixed or reacted with species present on device  10 . The biological cells are either procaryotic and/or eucaryotic cells. Examples of procaryotic cells include, but are not limited to, bacteria, microorganisms, etc. Examples of eucaryotic cells are, but not limited to, fungal, plant and animal cells for instance mammalian cells or human cells. In more particular embodiments, the mammalian or human cells may be cells for example, from blood, liver, kidney, lung or any other tissue or organ. In another preferred embodiment, the cells are tumor or cancer cells, which can be either benign or malignant cancer cells.  
         [0053]    In a typical embodiment of the thermal fluidic device, the width of the patterned hydrophilic pathways will range from a few micrometers to hundreds of micrometers. Liquid samples deposited onto the reservoirs or hydrophilic pathways can range from less than a microliter to tens of microliters. The liquids flowing along the hydrophilic pathways can range in thickness from about a micron to tens or hundreds of microns, depending on the degree of hydrophobicity of the surrounding material. The more hydrophobic is the surrounding surface to the hydrophilic liquid, the thicker the liquid stream or droplet that can be confined by the chemical patterning. A range of thermal gradients can be applied to the chemcially patterned surface so long as the liquid does not substantially evaporate or boil. Typical thermal gradients can range from a few degrees per centimeter to tens of degrees per centimeter. The speed of the flowing liquid depends on material properties like the liquid surface tension, the variation of surface tension with temperature and the liquid viscosity. The speed also depends on the magnitude of the applied thermal variation with distance (i.e. the local or global thermal gradient), as well as geometric features of the device like the surface area of the reservoir (which controls the volume of sample deposited), the width, length and shape of the hydrophilic pathway connecting source to target. Studies with liquids like tetraethylene glycol can produce speeds in the range of 600 micrometers per second. Designs with geometric and chemical patterning techniques that allow thicker films to flow onto a hydrophilic pathway can produce speeds of the order of a millimeter per second.  
         [0054]    [0054]FIG. 2 illustrates an arrangement of heating elements  16  in array  19 . Array  19  comprises a plurality of cells  20  arranged in a matrix configuration. As shown in FIG. 3, each individual cell  20  can be an integrated circuit comprising one or more transistors  21 , capacitors  21   b  and microheating elements  16 . Each heating element  16  sets the temperature of a respective cell  20 . Each cell  20  is addressed by thin film transistor switch  21   a . Transistor  21   a  switches power to capacitor  21   b  and transistor  23 . Voltage on transistor  23  sets current through capacitor  23  thereby regulating its temperature heating element  16 . In this embodiment, the matrix configuration is a  3 -by- 3  matrix. It will be appreciated that alternate size matrices can be used depending on the size of device  10  or the desired configuration of a thermal map associated with the matrix configuration. Heating elements  16  are selected to have a predetermined size dependent on the desired size of device  10  and the desired positional resolution of the temperature profile. For example, heating elements  16  typically can have a width in the range of about 1 micron to about 5 mm. VDD is a power supply voltage to cell  20 . Liquid streams or droplets can be moved from one cell  20  to another cell  20  with a speed determined by the applied thermal map, the liquid viscosity, the surface tension and the variation in surface tension with temperature. Cells  20  can be activated at a rate faster than the rate of fluid motion in order to establish the temperature of each cell  20  ahead of the fluid response. Liquid  24  responds by flowing from cells at higher temperature to cells at lower temperature.  
         [0055]    Alternative thermal maps can be applied to effect conformational changes to a liquid stream controlled by device  10  as shown schematically in FIGS. 4 a - d . The vertical axis is the temperature at a particular location (x,y) on the surface of device  10 . FIG. 4 a  describes the type of thermal map which will provide continuous streaming of a liquid rivulet or droplet across a series of cells  20 . FIG. 4 b  describes the action of a saw-tooth temperature profile which will divide a liquid rivulet into a series of discrete droplets. These droplets may be monodisperse or not depending on the particular thermal pattern applied and the lateral extent of the heating elements. FIG. 4 c  describes a thermal map for isolating and trapping a discrete droplet and subsequent heating and cooling to initiate or quench a chemical reaction. After the droplet has been appropriately manipulated, the thermal map shown in FIG. 4 d  can be applied for release and further migration onto another cell  20 , a reservoir or exit port from the device.  
         [0056]    In one embodiment of the present invention, surface layer  18  is patterned with network  29  of intersecting pathways, as shown in FIG. 5. Surface layer  18  can be formed of a hydrophilic material for forming hydrophilic pathways between hydrophobic regions.  
         [0057]    Horizontal pathways  30   a - 30   c  extend respectively between reservoirs  31   a - 31   c  and reservoirs  32   a - 32   c . Vertical pathways  33   a - 33   c  extend respectively between reservoirs  34   a - 34   c  and reservoirs  35   a - 35   c . Each of horizontal pathways  30   a - 30   c  intersects vertical pathways  33   a - 33   c . A matrix of cells can be in registry with horizontal pathways  30   a - 30   c  and vertical pathways  33   a - 33   c  for controlling flow from respective reservoirs (not shown). First reagent  36   a  is dispensed into reservoir  34   b  and second reagent  36   b  is dispensed from reservoir  34   c . First reagent  36   a  can be the same or different than second reagent  36   b . Third reagent  36   c  is dispensed from reservoir  30   a . Each of first reagent  36   a , second reagent  36   b  and third reagent  36   c  flows toward fluid reservoir  35   c . First reagent  36   a  and third reagent  36   c  flow in pathway  30   a  and are mixed with one another to form a homogeneous composition. Second reagent  36   b  flows into pathway  33   c  and is mixed with the mixture of first reagent and third reagent  36   c  flowing in pathway  33   c  toward reservoir  35   c  to form a homogeneous composition. A chemical reaction between two or more of reagents  36   a -  36   c  or an entity such as a molecule, particle or droplet immobilized in one of channels  30   a ,  33   c  or reservoir  35   c  can occur spontaneously or can be induced by activation of one or more heating elements in registry with pathways  30 - 30   c  and  33   a - 33   c . It will be appreciated that various reagents can be dispensed from one or all of the pathways in network  29 .  
         [0058]    Liquid mixing can be achieved by placing liquid in contact with a differentially heated substrate. FIG. 6 a  is a cross sectional view illustrating the mixing of two liquids,  40  and  42 , residing on a hydrophilic region. Liquids  40  and  42  represent cross-sectional views of a discrete droplet or a liquid rivulet. In the absence of a lateral thermal gradient on substrate  44 , liquid  40  and  42  can only mix by interdiffusion. In the presence of a lateral thermal gradient on substrate  44 , liquids  41  and  42  mix by thermocapillary induced forcing to produce the mixing pattern shown in FIG. 6 b . For the case of a liquid made to flow by application of an additional thermal gradient perpendicular to the first, the spiral pattern shown will evolve into a helical one. The creation of additional interfacial area between liquids  40  and  42  produces significantly faster mixing. Reservoirs containing liquids to be dispensed can be patterned into a variety of shapes as illustrated in FIGS. 7 a - 7   c . Exemplary shapes include a square, circle or diamond. These can also be combined to produce rectangles, polygonal or curvilinear shapes.  
         [0059]    Alternative geometric layouts for surface pathways connecting two reservoirs are illustrated in FIGS. 8 a - 8   c . Network  50  represents a linear pathway  52  connecting reservoir  51  to  53 . Network  54  includes three linear pathways  52   a - 52   c  connecting reservoir  51  to  53 , as shown in FIG. 8 b . Network  55  consists of a sinuous pathway  56  connecting reservoir  51  to  53 , a shown in FIG. 8 c . Networks can comprise a source and a target reservoir connected by one or more pathways. The pathways can be rectilinear or curvilinear. The subsurface heater elements  16  are placed in registry with the network to achieve the desired flow pattern. The minimum number of heater elements required for controlling the flow of liquid into or out of a reservoir connected to N pathways equals N+1. One heater element is used for uniformly heating or cooling the reservoir pad while the remaining N heater elements function as valves to prevent or promote migration along the N pathways. The number of heater elements  16  used for controlling the flow of liquid along a pathway depends on the length L of the pathway and the desired spatial resolution D.  
         [0060]    [0060]FIGS. 9 a - 9   e  represent schematic diagrams of possible network variants connecting sets of reservoirs. FIG. 9 a  illustrates a network including a plurality of vertical pathways having a plurality of reservoirs interconnected to a horizontal pathway. FIG. 9 b  illustrates a schematic diagram of a network comprising rectilinear intersecting pathways. FIG. 9 c  illustrates a network comprising a radial arrangement of pathways. FIG. 9 d  illustrates a network including a plurality of vertical pathways intersecting a horizontal pathway. FIG. 9 e  illustrates a plurality of horizontal pathways connected by an intersecting sinuous pathway. It will be appreciated that networks can be arranged in alternative patterns or any combination of patterns for defining a desired flow of liquid in device  10  in accordance with the teachings of the present invention.  
         [0061]    Liquid samples can be introduced onto device  10  by using a variety of contact or non-contact dispensing techniques. In addition, the liquid sample can be placed onto a reservoir or injected directly onto a pathway. One non-contact dispensing method is ink-jetting. Contact dispensing methods include pin tool spotting, pressurized capillary tubes or syringe tips. FIG. 10 a  illustrates a sample deposition tool  60  delivering material onto a circular reservoir pad  61 . FIGS. 10 b - e  represent liquid deposition directly onto respective pathways  62   b - e . The pathways can have square, round or tapered edge termination.  
         [0062]    [0062]FIGS. 11 a - 11   b  illustrate an exemplary use of device  100  in accordance with the teachings of the present invention for detecting airborne chemicals in gaseous, particulate or aerosol form by absorption onto a liquid surface. Device  100  comprises network  102  which comprises rectilinear pathways  104   a - 104   c  between respective source reservoirs  105   a - 105   c  and target reservoirs  106   a - 106   c.    
         [0063]    Input  107  dispenses one or more reagents to one or more of source reservoirs  105 - 105   c . For example, input  107  can be a microsyringe. Network  102  resides on surface  108 . Liquids received on network  102  can absorb airborne chemical species  109  while flowing on pathways  104   a - 104   c . The liquid flow is enforced via differential heating from source reservoir  105  to target reservoir  106 . This differential heating is accomplished through heat source  111 , which is coupled to bottom surface  112  at edge  114 , and heat sink  113  located at edge  116  of device  100 . Heat sink  113  can be formed by flowing coolant substance  117  through interior  115  of metal tube  118 . If substrate  122  is formed of silicon or a metal, a linear temperature profile can be made to develop along pathways  104   a - 104   c . Other temperature profiles are possible in accordance with the teachings of the present invention.  
         [0064]    Heat source  111  is placed in registry with source reservoirs  105   a - 105   c . Heat source  111  can be a single activated heat source such as a flexible metal heater insulated with Kapton foil (e.g. Omega Engineering Inc. model KHLV-0502/10-P). Heat source  111  can be attached to bottom surface  112  of substrate  122  by means of glue or adhesive material. Alternatively, for transport along more curvilinear pathways  104 , the differential heating can be accomplished through a plurality of cells  20  or heater elements  16  which are located beneath pathways  104  and individually electronically activated.  
         [0065]    Device  100  and device  10  can be utilized with a number of detection schemes. One such method can include deposition of various inhibited fluorescent liquid compounds onto reservoirs  105   a - c  which when contacted by an airborne agent either emit light directly or can be made fluorescent by further optical excitation. The fluorescence can be detected by optical sensors  120 . A suitable optical detector assembly  120  comprise a laser diode, optical filters and a light detector probing target reservoirs  106   a - 106   c . Alternatively, optical sensors can be positioned along one or more of pathways  104   a - 104   c . Other detection methods can include monitoring color changes(with or without fluorescence), electrical conductivity, refractive index, light absorption, or temperature. Electrochemical detectors can also be used. It will be appreciated that alternative methods for detecting airborne species could be used in accordance with the teachings of the present invention. The species can be introduced onto device  100  by passive absorption or by convective gas streams running perpendicular to pathways  104   a - c.    
         [0066]    [0066]FIG. 12 is a flow diagram of an exemplary process for fabrication of device  10  and corresponding results of each of the steps. In this description of the fabrication process flat topologies are used. The initial cleaning of substrate  12  is shown in block  70 . The particular cleaning procedure is dependent on the substrate material. For instance, glass can be cleaned by ultrasonic agitation in organic solvents and immersion in sulphuric acid and hydrogen peroxide. Block  71  represents the optional deposition of a passivation or adhesion layer  9 . This can be accomplished, for example, by spin coating a thin layer of spin-on glass or chemical vapor deposition of silicon nitride. This layer serves to promote adhesion of insulation layer  14  to substrate  12  or to create a reproducible and well characterized (i.e. passivated) surface on top of which subsequent layers can be deposited. Block  72  represents an optional thermal and insulation layer which, for example, can be accomplished by spin coating a thin layer of polyimide which is then baked for imidization. This layer reduces the power input required to maintain a desired temperature distribution and prevents electrical contact between heating elements  16  and substrate  12 . Block  73  depicts the deposition of heating elements  16 . Heating elements  16  can be micropatterned including current leads for power input. Heating elements  16  can be formed of a conductive metal such as titanium, platinum, gold or chromium, or a non-metallic conductor such as silicon or indium tin oxide Heating elements  16  can be deposited by photolithographic patterning of a photoresist layer and subsequent pattern transfer into the resistive heating material. Alternatively, heating elements  16  can be deposited by thermal evaporation of the metallic or non-metallic conductor or by other deposition methods.  
         [0067]    In block  74 , electrical insulator layer  17  is deposited over heating elements  16  and insulating layer  14  or substrate  12 . For example, electrical insulator layer  17  can be deposited as a layer of silicon oxide. An additional planarization and/or passivation layer  8  can be introduced to provide a smooth, flat and reproducible surface for subsequent hydrophilic/hydrophobic surface patterning. Electrical insulator layers  17  and/or passivation layer  8  provide additional protection of device  10  from moisture invasion. An exemplary method for performing planarization is by depositing a material such as a polymeric material or spin on glass onto heating elements  16  and insulator layer  14  or substrate  12 . An implementation of a passivation layer includes plasma enhanced deposition of a silicon nitride passivation layer. In an alternate method, the fabrication method starts with substrate  12  including cells comprising transistors  21  and leads for a matrix addressing scheme of cells  20 . Before deposition of heating elements  16 , contacts through insulator layer  14  and electrical insulation layer  17  are formed. Alternatively, heating elements  16  can be formed below insulator layer  14 .  
         [0068]    Block  75  depicts a chemical patterning step of surface  18 . In one embodiment surface  18  is first prepared to be completely hydrophobic. Thereafter, surface  18  is then selectively patterned to reveal hydrophilic regions such as reservoirs  105  and  106  or pathways  104 . The chemical patterning step, however, need not be subtractive, as described below. An additive method in which the hydrophilic layer  18  is selectively stamped with hydrophobic material to produce a surface of mixed wettability. Surfaces of mixed wettability comprising hydrophilic and hydrophobic regions are used to confine and direct liquids on substrates such as glass, silicon, Kapton and other polymeric materials. In one embodiment, hydrophilic or hydrophobic surface patterns are used to form networks in device  10 . Hydrophilic and hydrophobic surface patterns can be fabricated to be refreshable for re-establishing the coating after it has been removed, such as by mechanical abrasion or chemical attack induced by repeated use.  
         [0069]    Conventional methods for creating hydrophobic surfaces include silanization or thiolization. Treatment with organic solutions containing octadecyltrichlorosilane or perfluorinated compounds, such as fluorinated trichlorosilane, produce strongly hydrophobic surfaces on which water droplets assume contact angles in excess of about  90  degrees. FIG. 13 illustrates a hydrophobizing scheme which uses alkylthiol compounds on gold. An attractive feature of this method is that undesired abrasion or chemical attack resulting from repeated use of the device can be healed by simply refreshing the hydrophobic portions of surface  18  comprising the gold coated regions. Only these regions attract and bind the thiolized solution. Patterning of the hydrophobic layer can be performed by photolithography, reactive ion etching in an oxygen plasma or exposure to ultraviolet light.  
         [0070]    The flow diagram shown in FIG. 13 can in practice also be used independently of device  10  for uses requiring liquid sample confinement on a substrate containing no heating elements. It can also be used on surfaces which are uniformly heated or cooled as in a microreactor plate. The flow diagram illustrates the method for fabricating refreshable hydrophilic and hydrophobic surface patterns. These process steps can also be performed on top of layer  17  following the process step shown in block  74 .  
         [0071]    In block  200 , surfaces of the material on substrate  12  are cleaned. In an embodiment of the device, substrate  12  is a silicon wafer or glass plate. The material on substrate  12  can be immersed in sulfuric acid, hydrogen peroxide and deionized water at elevated temperatures. Cleaning of polymeric materials requires reagents compatible with the chemical resistance of the material on substrate  12 . In block  201 , a layer of Cr is evaporated. The layer of Cr can have a thickness between about 1 and about 10 nanometers. In block  202 , a layer of Au is evaporated. This layer of Au can have a thickness between about 1 to about 500 nm. In block  203 , photoresist is spin coated onto the Au coated surface. In block  204 , the photoresist is patterned by application of a mask and photolithographic processing for developing the exposed photoresist. In block  205 , a pattern is etched into the Au layer. A suitable etching technique can be wet chemical etching (TFA from Transene Comp. Inc). In block  206 , any remaining photoresist is removed. In block  207 , the Au surface is coated with a hydrophobic material. Suitable hydrophobic substances include alkylthiols like hexadecanethiol. A monolayer of this material can be applied by immersion of the Au surface into a solution of alkylthiol in ethanol. The thiol molecules are known to bond selectively to Au surfaces. The thiol molecules will not bond to substrates such as glass, silicon or Kapton. In block  208 , if any of the hydrophobic material is removed by mechanical abrasion or chemical attack, the gold surface can then be reimmersed into the hydrophobic solution for material selective refreshing of the hydrophobic coating.  
         [0072]    In an alternate method of fabricating refreshable surface patterns, blocks  201 - 205  can be substituted with a lift off process in which a layer of photoresist is patterned before the metal coating is evaporated. Alternatively, titanium can be used in step  201  and evaporated by the use of an electron beam evaporator.  
         [0073]    The hydrophilicity of a chemcially patterned substrate can be maintained by storing it in glycerol (C 3 H 5 (OH) 3 , 1,2,3-propanetriol). The glycerol can be applied by brushing, dipcoating or other coating technique. Once coated with a layer of glycerol, device  10  can be stored without degradation or organic contamination of the hydrophilic regions for extended periods of time. Upon use, the glycerol coating can be removed by washing the surface with deionized water and drying by a filtered gas stream like dry nitrogen. Glycerol does not adhere to hydrophobic coatings and does not readily evaporate at room temperature. If the glycerol coated substrates are placed in a refrigerated environment, the glycerol will thicken to produce a gel-like protective coating. Since glycerol is hygroscopic, storage in an airtight container is preferable.  
         [0074]    It is to be understood that the above-described embodiments are illustrative of only a few of the many possible specific embodiments which can represent applications of the principles of the invention. Numerous and varied other arrangements can be readily devised in accordance with these principles by those skilled in the art without departing from the spirit and scope of the invention.  
         [0075]    The thermal fluidic device described above can be used for applications involving functional genomics and recombinant DNA methods. It can also be used for microarray immunoassays in microfluidic triage protein chips.  
         [0076]    The invention described is also broadly applicable as a diagnostic and/or synthetic tool. Unlike other microfluidic technologies, its design enables manipulation, transport, and analysis of both droplets and continuous streams. It also uses only one single mechanism (i.e. an addressable thermal matrix array) to enforce precise dosing, transport, mixing and chemical reactions. Allowing multiple and parallel reactions, the chip is ideally suited to the synthesis and screening of specialized inorganic, organic or genomic materials in the nano- to picoliter range by spatial and temporal multi-step manipulation of droplets. The manipulation and control of liquid samples can be used for fundamental studies, like the interrogation and modification of rate constants, molecular activity and macromolecular conformation and phase changes in ultraconfined geometries in a completely automated manner producing quantities in the nano- to picoliter range. The device can also be used as a micro or nano-synthesis plate in which multiple organic or inorganic materials can be combined to form novel materials.  
         [0077]    The invention described can also be used in combination with more traditional lab-on-a-chip devices which typically use pneumatic or electrokinetic mechanisms for flowing, sorting, sizing and quantitating biological material like nucleic acids. It also lends itself to high throughput applications.  
       EXAMPLE  
     Example I  
       [0078]    Prototypes for the sensor device depicted in FIGS. 11 a  and  11   b  have been fabricated using the following process steps:  
         [0079]    1. Cutting of silicon wafers into 2-by-2 inch pieces.  
         [0080]    2. Cleaning of silicon samples by rinsing with or ultrasonication in tetrachlorethylene, acetone and isopropanol.  
         [0081]    3. Further cleaning of silicon samples by immersion into a mixture of sulfuric acid, hydrogen peroxide and deionized water at a temperature of 80° C. for 20 minutes.  
         [0082]    4. Deposition of a 120 nm thick layer of silicon dioxide by plasma enhanced chemical vapor deposition using a Plasmatherm 790 at a temperature of 250° C.  
         [0083]    5. Deposition of a 120 nm thick layer of silicon nitride by plasma enhanced chemical vapor deposition using a Plasmatherm 790 at a temperature of 250° C.  
         [0084]    6. Deposition of a 120 nm thick layer of silicon dioxide by plasma enhanced chemical vapor deposition using a Plasmatherm 790 at a temperature of 250° C.  
         [0085]    7. Spin coating of a layer of photoresist (AZ5214 at 4000 rpm for 40 seconds), exposure to UV radiation in a Karl Suess MJB3 mask aligner with a photolithographic mask for the heating electrodes and development of photoresist using a Clariant 400k developer  
         [0086]    8. Evaporation of 5 nm thick layer of titanium, a 120 nm thick layer of Au and a 5 nm thick layer of Cr using a Denton electron beam evaporator.  
         [0087]    9. Removal of resist by immersion into acetone, which leaves the desired metal heater and contact pads on the surface.  
         [0088]    10. Deposition of a 600-800 nm thick silicon dioxide layer by plasma enhanced chemical vapor deposition using a Plasmatherm 790 at a temperature of 250° C. with electrical contacts masked.  
         [0089]    11. Spin-coating of a layer of photoresist (AZ5214 at 4000 rpm for 40 seconds), exposure to UV radiation in a Karl Suess MJB3 mask aligner with a photolithographic mask for straight parallel hydrophilic channels and development of the photoresist using Clariant 400k developer.  
         [0090]    12. Immersion of sample in a dilute (1 mM) solution of 1H,1H,2H,2H-perfluorooctyltrichlorosilane in dodecane for 5 min.  
         [0091]    13. Removal of sample from solution and sonication of sample in dodecane for 1-5 minutes.  
         [0092]    14. Sample dried in stream of filtered nitrogen gas followed by a water rinse.  
         [0093]    15. Rinsing of sample with acetone to remove photoresist.  
         [0094]    16. Immersion of sample in Bakerstrip 1000 at a temperature of 60° C. for 5 minutes.  
         [0095]    17. Rinsing of sample with acetone and isopropanol.  
         [0096]    18. Removal of silicon dioxide and chromium on top of contact pads using chromium etchant CR-7  
         [0097]    19. Soldering of contact pads with In-solder.  
         [0098]    20. Cleaning of hydrophilic regions with a dilute solution of sulfuric acid and hydrogen peroxide in deionized water.  
         [0099]    21. Powering heating resistor with DC-power supply.  
         [0100]    22. Placing edge of sample opposite to heater wire on water cooled brass block.  
         [0101]    23. Deposition of hydrophilic liquid on the hydrophilic regions produces controllable and predictable liquid flow.  
       Example II  
       [0102]    Another prototype for the sensor device depicted in FIG. 1 b  and  1   c  has been fabricated using the following process steps:  
         [0103]    1. Cutting of silicon wafers in 2-by-2 inch pieces  
         [0104]    2. Cleaning of silicon samples by rinsing with or ultrasonication in tetrachlorethylene, acetone and isopropanol  
         [0105]    3. Further cleaning of silicon samples by immersion into a mixture of sulfuric acid, hydrogen peroxide and deionized water at a temperature of 80° C. for 20 minutes.  
         [0106]    4. Spin-coating of a layer of photoresist (AZ5214 at 4000 rpm for 40 seconds), exposure to UV radiation in a Karl Suess MJB3 mask aligner with a photolithographic mask for straight parallel hydrophilic channels and development of the photoresist using Clariant 400k developer  
         [0107]    5. Immersion of sample in a dilute (1 mM) solution of 1H,1H,2H,2H-perfluorooctyttrichlorosilane in dodecane for 5 ml.  
         [0108]    6. Removal of sample from solution and sonication of sample in dodecane for 1-5 minutes.  
         [0109]    7. Sample dried in filtered nitrogen gas stream followed by a water rinse.  
         [0110]    8. Rinsing of sample with acetone to remove photoresist.  
         [0111]    9. Immersion of sample in Bakerstrip 1000 at a temperature of 60° C. for 5 minutes  
         [0112]    10. Rinsing of sample with acetone and isopropanol  
         [0113]    11. Removal of silicon dioxide and Cr on top of contact pads using chromium etchant CR-7  
         [0114]    12. Soldering of contact pads with In-solder  
         [0115]    13. Cleaning of hydrophilic regions with a dilute solution of sulfuric acid and hydrogen peroxide in deionized water  
         [0116]    14. Place one edge of sample on heated, temperature controlled brass block.  
         [0117]    15. Place opposite edge of sample on water cooled brass block.  
         [0118]    16. Deposition of hydrophilic liquid on the hydrophilic regions produces controllable and predictable liquid flow. Proof of concept of this device was accomplished with a surface network consisting of a parallel set of rectilinear hydrophilic stripes each connecting two diamond shaped reservoirs. Only one resistive heater was patterned on the underside of a silicon substrate. The resistive heater assumed the shape of a long narrow stripe which ran perpendicular to the flow direction. The heater stripe warmed the surface at the point where the liquid exits the reservoir and enters the hydrophilic stripe. Various hydrophilic liquid samples (e.g. polydimethylsiloxane, glycerol, or tetraethylene glycol) were each deposited onto a different reservoir pad and the liquids spread in a predictable and controllable fashion. The liquid speed was found to be well correlated to the power applied to the resistor (which determines the temperature difference between the heated and the cooled sample edge), the width of the hydrophilic stripe and the volume of liquid deposited. Higher power inputs, wider hydrophilic stripes, thicker rivulets and larger sample volumes produced faster flow rates. Liquids with lower viscosity or stronger variation of surface tension, y with temperature T (i.e. higher dγ/dT) produced correspondingly faster speeds.  
       Example III  
       [0119]    A prototypes for the microfluidic routing device depicted in FIG. 1 a  has been fabricated using the following process steps:  
         [0120]    1. Cleaning of a 2-by-2 inch piece of Corning 1737 glass with a thickness of 0.7 mm by rinsing with (or ultrasonication in) tetrachlorethylene, acetone and isopropanol.  
         [0121]    2. Further cleaning by immersion into a mixture of sulfuric acid, hydrogen peroxide and deionized water at a temperature of 80° C. for 20 minutes.  
         [0122]    3. Spin coating of a layer of photoresist (AZ5214 at 4000 rpm for 40 seconds), exposure to UV radiation in a Karl Suess MJB3 mask aligner with a photolithographic mask for the heating electrodes and development of photoresist using Clariant 400k developer.  
         [0123]    4. Evaporation of 120 nm thick layer of Ti, a 100 nm thick layer of Au and a 5 nm thick layer of Cr using a Denton electron beam evaporator  
         [0124]    5. Removal of resist by immersion into acetone, which leaves the desired metal heater and contact pads on the surface.  
         [0125]    6. Deposition of a 600-800 nm thick silicon dioxide layer by plasma enhanced chemical vapor deposition using a Plasmatherm 790 at a temperature of 250° C. with electrical contacts masked.  
         [0126]    7. Spin-coating of a layer of photoresist (AZ5214 at 4000 rpm for 40 seconds), exposure to UV radiation in a Karl Suess MJB3 mask aligner with a photolithographic mask for straight parallel hydrophilic channels and development of the photoresist using Clariant 400k developer.  
         [0127]    8. Immersion of sample in a dilute (1 mM) solution of 1H,1H,2H,2H-perfluorooctyltrichlorosilane in dodecane for 5 min.  
         [0128]    9. Removal of sample from solution and sonication of sample in dodecane for 1-5 minutes.  
         [0129]    10. Drying of sample in filtered nitrogen stream following by a water rinse.  
         [0130]    11. Rinsing of sample with acetone to remove photoresist.  
         [0131]    12. Immersion of sample in Bakerstrip 1000 at a temperature of 60° C. for 5 minutes.  
         [0132]    13. Rinsing of sample with acetone and isopropanol.  
         [0133]    14. Removal of silicon dioxide and Cr on top of contact pads using chromium etchant CR-7.  
         [0134]    15. Optional soldering of contact pads with In-solder.  
         [0135]    16. Cleaning of hydrophilic regions with a dilute solution of sulfuric acid and hydrogen peroxide in deionized water.  
         [0136]    17. Powering heater resistor with DC-power supply and alligator clips attached to the device.  
         [0137]    18. Sample placed on water cooled brass block which acts as heat sink.  
         [0138]    It is to be understood that the above-described embodiments are illustrative of only a few of the many possible specific embodiments which can represent application of the principles of the invention. Numerous and varied other arrangements can be readily devised in accordance with these principles by those skilled in the art without departing from the spirit and scope of the invention.