Abstract:
A device for flowing a liquid on a surface comprises: a flow path. A first port supplies the liquid to one end of the flow path and applies a first port pressure for retaining the liquid when the flow path is remote from the surface. A second port receives the liquid from the other end of the flow path and applies a second port pressure such that the difference between the first and second negative port pressures is oriented to promote flow of the liquid from the first port to the second port via the flow path in response to the flow path being located proximal to the surface and the liquid in the device contacting the surface. The first and second port pressures are such that the liquid is drawn towards at least the second port in response to withdrawal of the flow path from the surface. Such devices may employ microfluidic technology and find application in surface patterning.

Description:
BACKGROUND OF THE INVENTION  
       [0001]     The present invention generally relates to a method and device for flowing a liquid on a surface.  
         [0002]     There are many applications in which it is desirable to flow a liquid on a surface. An example of such an application is in patterning or other processing of surfaces. Patterning and processing of surfaces with liquids is becoming increasingly important in a range of fields, including chemistry, biology, biotechnology, materials science, electronics, and optics. Patterning a surface by applying a liquid to the surface typically involves confinement of the liquid to defined regions of the surface.  
         [0003]     A surface is typically wettable by a liquid if the contact angle between a drop of the liquid and the surface is less than 90 degrees. A channel for carrying a liquid is typically wettable if the channel exerts a negative pressure on the liquid when partially filled. Such a negative pressure promotes filling of the channel by the liquid. In a channel having a homogeneous surface, a negative pressure arises if the contact angle between the liquid and the surface is less than 90 degrees. A surface is typically regarded as more wettable if the contact angle between the surface and the liquid is smaller and less wettable if the contact angle between the surface and the liquid is higher.  
         [0004]     One conventional surface patterning technique is lithography. In lithography, a mask is usually applied to the surface to be patterned. Apertures are formed in the mask to define regions of the surface to be exposed for treatment. Those areas of the surface remaining covered by the mask are protected from treatment. The mask is typically formed from a patterned layer of resist material. The surface carrying the mask is then typically immersed in a bath of chemical agents for treating the exposed regions of the surface. Lithography is a relatively expensive process to perform, involving multiple steps. With the possible exception of in situ synthesis of short DNA strands, lithography is generally unsuitable for handling and patterning biomolecules on surfaces. Lithography is also unsuitable for simultaneously processing surfaces with different chemicals in parallel, as described by Whitesides,  Annu. Rev. Biomed.  3 (2001), 335-373.  
         [0005]     There can be incompatibility between different process steps or chemicals used in lithography and between various surface layers processed by lithography.  
         [0006]     Another conventional surface patterning technique is drop delivery. Drop delivery systems, such as pin spotting systems, ink jet systems, and the like, typically project a relatively small volume of liquid onto a specific location on a surface. See Shena, M., “ Microarray biochip technology ”, Eaton Publishing 2000. However, these systems have limited resolution due to spreading of dispensed drops on the surface. Additionally, the quality of patterns formed by such systems is strongly limited by drying of the delivered liquid, as described by Smith, J. T., “ Spreading Diagrams for the Optimization of Quill Pin Printed Microarray Density”,  Langmuir, 18 (2002), p 6289-6293.  
         [0007]     These systems are not generally useful for dissolving or extracting materials from a surface. Additionally, these systems do not facilitate a flow of liquid over a surface. Furthermore, these systems are not suited to process a surface sequentially with several liquids.  
         [0008]     PCT WO 01/63241 A2 describes a surface patterning technique involving a device having a channel with a discharge aperture. A matching pillar is engaged with the discharge aperture to promote deposition of molecules on the top surface of the pillar. A disadvantage with this device is that it is not possible to vary patterning conditions for different pillars individually. Another disadvantage is that it is not capable of establishing a flow on a surface. Exposure of the surface to the liquid needs to be sufficiently long to allow reagents to reach the surface by diffusion. The method also requires a surface with pillars matching the aperture. Fabrication of such a surface requires expensive clean-room equipment and etching tools. This can increase cost per patterned surface. Precise alignment of the device with the pillars before engagement is required. Additionally, the pillars need pretreatment to ensure the confinement of the liquid. Spacing between the discharge aperture and the pillars needs external control.  
         [0009]     Yet another conventional surface patterning technique involves application of a microfluidic device to the surface. An example of such a device is described in U.S. Pat. No. 6,089,853. The device described therein can establish a flow of liquid over a surface. The flow can be created via capillary action in the device. The device can treat a surface with multiple different liquids in parallel. However, the device must be sealed to the surface in the interests of confining the liquid to the region of the surface to be treated. Such confinement allows the formation of patterns with relatively high contrast and resolutions. These are desirable qualities where biomolecules are patterned on a surface for biological screening and diagnostic purposes.  
         [0010]     In addition, the device must be placed on the surface to be treated and sealed around the processing regions before it can be filled with treatment liquid. If the flow is created by capillary action, other problems arise. For example, service ports in the device must be filled with treatment liquid for each patterning operation. In addition, only one liquid can be delivered to each channel in the device. The liquid cannot be flushed out of the or each channel before separation of the device from the surface. Furthermore, the treatment liquid tends to spread away from the regions of the surface to be treated during removal of the device from the surface.  
         [0011]     Also, the device is not suitable for processing a surface sequentially with several liquids. If the flow is created by external actuation, such as pressurization, electric fields, or the like, then other problems arise. For example, an individual connection from the actuator must be made to each channel in the device. Such connections to peripheral equipment limit the density of channels that can be integrated into the device and individually addressed. Pumping, valving, and control complexity increases as the number of channels increases. External connections create dead volume between the device and external actuators because of the intervening conduits.  
         [0012]     Another microfluidic device for localized processing of a surface is described in  IBM Technical Disclosure Bulletin reference RD n 446  Article  165  Page  1046. This device is similar to that described in U.S. Pat. 6,09,853. The device permits several liquids to be flushed in sequence over the same surface area without requiring separation of the device from the surface. Such a device is thus useful for chemical and biological reactions involving the sequential delivery of several liquids. A disadvantage associated with this device however is that it must be sealed around the region of the surface to be treated before filling. Another disadvantage is that the liquids cannot be filled prior to application on the device to the surface. Each additional step requires supplementary filling of the relevant liquid. Another disadvantage is that the device cannot be removed from the surface while the service ports contain liquid without liquid spreading over the surface beyond the region to be exposed.  
         [0013]     Another conventional device for confining liquids to a predefined pattern between a top and bottom surface without involving a seal is described in European Patent 0 075 605. This device is useful for performing optical analysis of a liquid trapped between the top and bottom surface. However, the device requires predefined topographical or chemical patterns on both the top and bottom surfaces. Also, the device, having no inlet or outlet ports, is not suitable for the transport of liquids.  
         [0014]     Another device for guiding liquids along a predetermined path is described in WO 99/56878. This device can flow several liquids simultaneously over a surface without involving seal to confine the liquids. However, a disadvantage of this device is that separation gaps between paths have to be capillary inactive. This limits path sizes to greater than  1  mm. Otherwise meniscus pressures produce uncontrolled spreading of liquid. Another disadvantage of this device is that liquid is not retained after separation and can instead spread over the surface. A further disadvantage of this device is that liquid delivery requires an external connection to each path. Cumbersome peripheral flow control devices are also required.  
         [0015]     Yet another method for guiding liquid along a surface without involving a seal is described in Zhao et al.,  Science,  Vol. 291 (2001), p. 1023-1026. Here, the surface is patterned with a wettability pattern. Specifically, two wettable paths mirroring each other are defined on otherwise non-wettable top and bottom surfaces. This produces “virtual” channels without lateral walls that can have micrometer width. A disadvantage of this method is that it requires wettability patterns on both the top and bottom surfaces. Additionally, the wettability contrast between the two patterns needs to be very high, and requires both non-wettable areas on the top and bottom surfaces and highly wettable areas within the virtual channel. Furthermore, the two patterns have to match each other exactly in shape and alignment. Capillary action can used to fill the channels, but the liquid cannot be removed or exchanged. This method is also susceptible to uncontrolled spreading of liquid because it is relatively difficult to produce sufficiently non-wettable surfaces. A external pump may be used to deliver the liquid, but if the pump pressure exceeds a relatively low level, liquid will overflow the defined flow path. Furthermore, external pumping requires external connections to each flow path, thus limiting integration. As indicated earlier, external connections create dead volume in pump connecting conduits.  
         [0016]     It would be desirable to provide a technique for flowing a liquid over a surface in a more versatile and convenient manner.  
       BRIEF SUMMARY OF THE INVENTION  
       [0017]     In accordance with the present invention, there is now provided a device for flowing a liquid on a surface, the device comprising: a flow path; a first port for supplying the liquid to one end of the flow path and for applying a first port pressure for retaining the liquid when the flow path is remote from the surface; a second port for receiving the liquid from the other end of the flow path and for applying a second port pressure such that the difference between the first and second negative port pressures is oriented to promote flow of the liquid from the first port to the second port via the flow path in response to the flow path being located proximal to the surface and the liquid in the device contacting the surface; and, the first and second port pressures being such that the liquid is drawn towards at least the second port in response to withdrawal of the flow path from the surface.  
         [0018]     The devices preferably comprises a protrusion extending into the flow path adjacent the first port for directing the liquid from the first port towards the surface. The protrusion may be formed from a resilient material to prevent damage to the device and/or surface. The device may comprise a peripheral flange surrounding the flow path for sealing the flow path to the surface when the device is proximal to the surface. In a preferred embodiment of the present invention, the device comprises: a first opening communicating between the first port and the flow path for applying a first opening pressure to the liquid in the first port, the first opening pressure being more negative than the first port pressure; and, a second opening communicating between the flow path and the second port for applying a second opening pressure to the liquid in the flow path, the second opening pressure being more negative than the first port pressure.  
         [0019]     The device preferably, comprises sides less wettable by the liquid and sides more wettable by the liquid, wherein the flow path is located on a more wettable side surrounded by less wettable sides. In a particularly preferred embodiment of the present invention, the device comprises a body housing the first port and the second port and an extension protruding from the body to form the flow path, the first and second openings being disposed at opposite ends of the extension. Sides of the extension surrounding the flow path are preferably less wettable to the liquid than the flow path. The flow path is thus defined by and located at the extremity of the extension. A surface placed proximal and facing the extremity can form surface channel within the intervening gap. Liquid can be confined and guided within such a surface channel via interfacial tension without a physical seal. This effectively prevents trapping of bubble in the flow path. Entrapment of bubbles can adversely affect the flow rate of liquid. The flow path may be straight or curved.  
         [0020]     The first port may comprise a first capillary network for applying the first port pressure. The first capillary network may comprise at least one of a plurality of parallel capillary members, a mesh, a porous material, and a fibrous material. The second port may comprise a second capillary network for applying the second port pressure. The second capillary network may comprise at least one of a plurality of parallel capillary members, a mesh, a porous material, and a fibrous material. The device may comprise a plurality of first ports each coupled to the flow path. Similarly, the device may comprise a plurality of second ports each coupled to the flow path. The flow path may have a curved cross section.  
         [0021]     Alternatively, the flow path may have a rectangular cross section. Devices embodying the present invention may be of unitary construction and may be formed from any one of elastomer, silicon, SU-8, photoresist, thermoplastic, ceramic, and metal. Alternatively, devices embodying the present invention may be of layered construction, wherein each layer is formed from one of elastomer, silicon, SU-8, photoresist, thermoplastic, metal, and ceramic. In a particularly preferred embodiment of the present invention, the flow path is approximately 100 micrometers in length and approximately 100 micrometers in width, the volumes of first and second ports are 500 nanoliters each, and, in use, the protrusion defines a spacing between the device and the surface in region of between 5 and 10 micrometers. The first and second port pressures may be such that the liquid is drawn towards the first port and the second port in response to withdrawal of the flow path from the surface. The present invention also extends to an array of applicator devices each as herein before described.  
         [0022]     Viewing the present invention from another aspect, there is now provided a method for flowing a liquid on a surface, the method comprising: supplying the liquid from a first port of an applicator device to one end of a flow path of the device; applying to the liquid a first port pressure via the first port; receiving the liquid from the other end of the flow path in a second port of the device; applying to the liquid via the second port a second port pressure different to the first port pressure; promoting, via the difference between the first and second port pressures, flow of the liquid from the first port to the second port via the flow path in response to the flow path being located proximal to the surface and the liquid therein contacting the surface; and, drawing, via the first and second port pressures, the liquid towards at least the second port in response to withdrawal of the flow path from the surface.  
         [0023]     The method may comprise, following withdrawal of the flow path from the surface, relocating the device at another position on the surface. Equally, the method may comprise, following withdrawal of the flow path from the surface, relocating the device on another surface. In a preferred embodiment of the present invention, the method comprises contacting the surface with the device and thereafter spacing the device from the surface to define a surface channel between the surface and the flow path for passage of the liquid from the first port to the second port. The method may comprise locating the device in a humid environment to initialize the flow of the liquid from the first port to the second port. The method may also comprise cooling the surface and/or the device to initialize the flow of the liquid via condensation. Alternatively, the method may comprise applying an electric field between the device and the surface to initialize the flow of the liquid from the first port to the second port. Equally, the method may comprise applying a pressure pulse to the liquid to initialize the flow of the liquid from the first port to the second port. Alternatively, the method may comprise applying a heat pulse to the liquid to initialize the flow of the liquid from the first port to the second port via vaporization of the liquid.  
         [0024]     In a preferred embodiment of the present invention, the method comprises reversing the direction of flow of the liquid by reversing the pressure difference between the first port and the second port. The method may also comprise drawing, via the first and second port pressures, the liquid towards the first and second ports in response to withdrawal of the flow path from the surface.  
         [0025]     In a particularly preferred embodiment of the present invention, there is now provided a device for flowing a liquid over a surface. The device comprises: a flow path; a first port for supplying the liquid to the flow path; a first opening communicating between the first port and one end of the flow path; a second port for receiving the liquid from the flow path; and, a second opening communicating between the other end of the flow path and the second port. In operation, engagement of the device with a surface initiates flow of the liquid from the first port to the second port via the flow path. The flow of liquid is curtailed by disengaging the device from the surface. Thus, the flow of liquid from the first port to the second port can be started and stopped by engaging and disengaging the device with the surface. The flow path acts as an operational fluidic channel when the device is engaged with the surface. This technology is hereinafter referred to as Surface Assisted Liquid Transfer technology or SALT technology. Accordingly, devices and modules based on this technology may be hereinafter referred to as SALT devices. The operational fluidic channel created by engaging the device with the surface will hereinafter be referred to as a surface channel.  
         [0026]     In SALT devices embodying the present invention, pressures in the first and second ports need not be varied during operation of the device. This is because engagement of the device with the surface creates a condition in which liquid automatically flows between the first and second ports. This condition can be freely disrupted by disengaging the device from the surface, again without requiring further control of the pressure in either of the first and second ports.  
         [0027]     The surface channel initially provides capillary action that transports the liquid from the first opening to the second opening. Thereafter, a pressure difference between first and second ports generates a flow of liquid from the first port to the second port. This effect is suppressed when the device is disengaged from the surface. Thus, the flow of liquid between first and second ports is curtailed. In a preferred embodiment of the present invention, the first port applies a negative pressure, P 1 &lt;0, to the liquid. Similarly, the second port applies a negative pressure to the liquid, P 2 &lt;0, P 2 &lt;P 1 . The pressure is thus such that the liquid flows from the first port to the second port when the surface channel is active. In a particularly preferred embodiment of the present invention, P 1  and P 2  are generated by capillary active structures or “capillary pumps”. The capillary pumps may comprise capillary networks as herein before described. The volumes of the first and second ports may be commensurate.  
         [0028]     An advantage associated with SALT devices is that they can be pre-filled with processing liquids for subsequent repetitive application and removal from areas of surfaces to be processed. Surface processing can be repeated multiple times from the same SALT device without refilling and thus delay. Another advantage associated with SALT devices is that they can deliver a series of different liquids and control the flow of each more easily than in conventional delivery techniques. Yet another advantage associated with SALT devices is that they can be swiftly mass produced via conventional microfabrication techniques. A further advantage of SALT devices is that they can include shallow conduits in processing areas to speed up mass-transport limited chemical reactions. An additional advantage of SALT devices is that they can employ minute amounts of processing reagents without depletion because the flow can be interactively controlled to renew the reagents as necessary.  
         [0029]     In typical applications, a SALT device can be placed at an arbitrary location on a surface and process parameters can be controlled via channel dimensions and contact time. Arrays of SALT devices are relatively easy to fabricate. In preferred embodiments of the present invention, flow control is integrated into each SALT device. Such arrays can comprise multiple independent fluidic zones to facilitate parallel processing of multiple areas of a surface with different liquids.  
         [0030]     SALT devices may be employed in many applications. For example, SALT devices can be employed to deposit biomolecules in selected regions of a surface to make bio-arrays, thus facilitating mass fabrication of bio-chips. SALT devices can be equally employed in subjecting selected areas of a surface to other processes, such as processes for: repairing pattern defects on a surface; etching specific areas of a surface; depositing metal on a surface; localizing an electrochemical reactions on a surface; depositing catalytic particles for electroless deposition of metals, deposition glass or latex beads or other particles on a surface; passivating specific areas of a surface; patterning proteins, DNA, cells, or other biological entities on a surface; making assays; staining cells; collecting cells, proteins, or other particles from a surface; retrieving analytes or specifically bound biomolecules from arrays on a surface; extracting DNA, proteins, or other molecules from gels; and, coupling collected cells or molecules to an analysis system.  
         [0031]     Examples of such an analysis system include liquid chromatography or electrophoresis systems. Devices embodying the present invention may be employed to flow the products of such an analysis system one or more areas of a surface. In other applications, the surface and/or the device may be transparent to permit optical monitoring of the flow and/or optical detection of molecules. In further applications, the surface may contain sensing systems, such as electrodes, membranes, wave guides, and associated transducers to permit detection of molecules in the liquid flowing over the surface. Other processes benefiting from SALT technology will be apparent. SALT devices can also be employed in the delivery of small volumes of samples to test regions formed in a surface. It will thus be appreciated that SALT technology may be employed in the detection of diseases and/or pollutants through the processing of specific areas of a surface.  
         [0032]     In accordance with another aspect of the present invention, there is now provided a device for applying a liquid to a surface, the device comprising a well for carrying the liquid, an opening in the well for communicating liquid from the well to the surface via a conduit having outer sides of limited wettability to the liquid. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0033]     Preferred embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:  
         [0034]      FIG. 1  is a cross sectional side view of a SALT applicator device embodying the present invention carrying a liquid;  
         [0035]      FIG. 2  is a cross sectional side view of the device in contact with a surface with flow of the liquid initiated;  
         [0036]      FIG. 3  is a cross sectional side view of the device during flow of the liquid;  
         [0037]      FIG. 4  is a cross sectional end view of the device during flow of the liquid  
         [0038]      FIG. 5  is a cross sectional side view of the device on removal from the surface;  
         [0039]      FIG. 6  is a cross sectional end view of an example of a first port for a SALT device embodying the present invention;  
         [0040]      FIG. 7  is a plan view of another example of a SALT device embodying the present invention;  
         [0041]      FIG. 8  is a cross sectional end view of a flow path for a SALT device embodying the present invention;  
         [0042]      FIG. 9  is a cross sectional end view of a flow path for a another SALT device embodying the present invention;  
         [0043]      FIG. 10  is a cross sectional side view of another SALT device embodying the present invention;  
         [0044]      FIG. 11 , is a cross sectional side view of a SALT device embodying the present invention used in combination with a patterned surface;  
         [0045]      FIG. 12 , is a cross sectional end view of the device used in combination with the patterned surface;  
         [0046]      FIG. 13  is a cross sectional side view of yet another SALT device embodying the present invention;  
         [0047]      FIG. 14  is a cross sectional side view of the device shown in  FIG. 13  in operation;  
         [0048]      FIG. 15  is a cross sectional end view of the device shown in  FIG. 13  in operation;  
         [0049]      FIG. 16  is a cross sectional side view of a further SALT device embodying the present invention;  
         [0050]      FIG. 17  is a cross sectional side view of a SALT array embodying the present invention;  
         [0051]      FIG. 18  is a cross sectional end view of the SALT array; and,  
         [0052]      FIG. 19  is a cross section side view of an interconnected SALT array embodying the present invention.  
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0053]     Referring first to  FIG. 1 , an example of a SALT applicator device embodying the present invention comprises a body  10  formed from a material such as PDMS, silicon, SU-8, photoresist, plastics, and metals. A first port  20  and a second port  30  are formed on one side of the body  10 . On the other side of the body  10  is narrow extension. A flow path  40  is defined is defined by the base  130  of the extension. The flow path may be straight or curved. A first opening  50  communicates between the first port  20  and one end of the flow path  40 . Similarly, a second opening  60  communicates between the second port  30  and the other end of the flow path  40 . The flow path  40  thus extends between the first port  20  and the second port  30 . In operation, the first port  20  acts as a fill port and the second port  30  acts as a flow promotion port. The liquid  70  is initially introduced to the first port  20 .  
         [0054]     The first port  20  holds the liquid  70  at pressure P 1 . P 1  is preferably negative. P 1 &lt;0. This contributes to retaining the liquid  70  in the first port  20 . The first opening  50  is wettable to the liquid and provides a capillary or meniscus pressure. This pressure exerts a negative first opening pressure OP 1 &lt;0 on the liquid  70  in the first port  20 . OP 1 &lt;P 1 . Therefore, OP 1  sucks the liquid from the first port  20  into the first opening  50  towards the flow path  40 . The first opening  50  widens at its intersection with the flow path  40 . The capillary pressure provided by the first opening  50  is therefore suppressed at this point. A protrusion  90  extends out of the body  10  into the flow path  40  adjacent the first opening  50 . The protrusion  90  is wettable by the liquid  70 . In operation, the protrusion sucks up the liquid  70  to its tip by capillary force. The protrusion may be resilient to prevent damage to the device or the surface  80 . In other embodiments of the present invention, there may be multiple protrusions  90  spaced along the flow path  40  to ensure that the surface channel  100  has uniform depth along its length.  
         [0055]     In some cases P 1  may vary and may be greater than or equal to  0 . This can arise, for example, when the first port  20  is overfilled with the liquid  70 . This leads to the liquid  70  having a convex surface. Such a surface is a source of positive pressure albeit of relatively low magnitude. In such a case, the opening  50  is filled with the liquid  70  up to the intersection with the flow path  40  and the protrusion  90 . Relatively small dimensions of both the opening  50  and the protrusion  90  are desirable for forming relatively high curvatures in the surface of the liquid  70 . By virtue of tension between the liquid and the surrounding medium, such curvatures produce relatively high pressures that confine the liquid  70  within the first port  20  and the opening  50  despite a positive pressure head.  
         [0056]     Initiation of flow from the first port  20  to the second port  30  will now be described with reference to  FIG. 2 . Engagement of the device with the surface  80  creates a surface channel  100  corresponding to the flow path  40 . The protrusion  90  abuts the surface  80  to define the size of the surface channel  100 , together with the flow path  40 . The surface channel  100  provides a capillary pressure, CP, that propels the liquid  70  from the first opening  50  to the second opening  60 . CP&lt;P 1  and CP&lt;0. The magnitude of CP is determined by the surface tension of the liquid  70 , the contact angles of the liquid  70  with the flow path  40  and the surface  80 , and the size of the gap formed between the flow path  40  and the surface  80 . It is thus possible to tune CP by varying the size of the gap between the surface  80  and the device. The smaller the gap, the higher the magnitude of CP. The larger the gap, the smaller the magnitude of CP.  
         [0057]     The surface  80  need not be completely flat, but can be rough, corrugated, porous, fibrous, and/or chemically inhomogeneous. It should also be appreciated that the flow path  40  can be filled with the liquid  70  even if the device is slightly tilted relative to the surface  80 . It may be possible to operate the device facing upwardly towards a downwardly facing surface. This may be possible especially where the operational dimensions of the device are very small, such that forces in the liquid interface exceed inertial forces. Gravity does not affect operation of such a device. It may be possible therefore to use such devices in reduced gravity environments.  
         [0058]     Confinement of the liquid  70  on the surface  80  is achieved via geometry and wettability of the device. The base  130  of the extension facing the surface  80  is made more wettable by the liquid  70 . However, side walls  110 - 120  of the extension are made less wettable by the liquid  70 . The liquid  70  does not spread out because of the right angle between the side walls  110 - 120  and the surface  80  and because of the less wettable properties of the side walls  110 - 120 . This confines the liquid  70  on the surface  80  to an area roughly corresponding to the area of the flow path  40 . Surfaces  200  and  210  of the base  130  are preferably made as small as practical in the interests of minimizing the area of the surface channel  100  which is not subject to flow of the liquid  70 .  
         [0059]     Confinement of the liquid  70  on highly wettable surfaces is enhanced by positioning the flow path  40  on the extension from the body  10 . Further enhancement in liquid confinement is achieved by maximizing the contrast in wettability between the more wettable and less wettable sides of the device. Where applications of interest involve only moderately wettable surfaces, the extension alone may achieve liquid confinement and accordingly the aforementioned wettability contrast may be reduced or omitted. Alternatively, in some applications, the extension from the body  10  may be omitted and liquid confinement achieved by the wettability contrast alone.  
         [0060]     Referring to  FIG. 3 , the second opening  60  provides a capillary or meniscus pressure. This pressure exerts a negative second opening pressure OP 2 &lt;0 on the liquid  70  in the flow path  40 . OP 2 &lt;P 1 . Thus, when the liquid  70  reaches the second opening  60 , it is drawn into the second opening  60  and propelled toward the second port  30 . In turn, the second port  30  exerts a negative pressure P 2 &lt;0 on the liquid  70 . P 2 &lt;P 1 . Thus, P 2  supports a flow of the liquid  70  from the first port  20  to the second port  30 . The flow rate is a function of the ratio (P 1 −P 2 )/Fr, where Fr is the flow resistance of the liquid  70  flowing from the first port  20  to the second port  30 .  
         [0061]      FIG. 4  shows a cross section through the device in a direction orthogonal to the flow path  40 . Similarly to side walls  110 - 120 , side walls  140 - 150  are less wettable to prevent spreading of the liquid  70  beyond the surface channel  100 . The capillary pressure retains the liquid  70  in the surface channel  100 .  
         [0062]     Referring to  FIG. 5 , if the gap increases, the magnitude of CP reduces. Eventually, CP reaches a threshold value. Below the threshold value, the liquid in the surface channel  100  drains first into the second port  30  and, provided that P 1 &lt;0, into the first port  20  shortly thereafter. The drainage causes disruption of the flow of liquid  70  from the first port  20  to the second port  30 . The flow of the liquid  70  from the first port  20  to the second port  30  can be curtailed simply by disengaging the device from the surface  80 . It is thus possible to initiate flow of liquid  70  from the first port  20  to the second port  30  by engaging the device with the surface  80  and to stop the flow by disengaging the device from the surface  80 .  
         [0063]     In a particularly preferred embodiment of the present invention, the flow path  40  is around 100 micrometers long and 100 micrometers wide, and the surface channel defining protrusion  90  extends from the base of the device by between 1 and 10 micrometers. The volumes of the first port  20  and the second port  30  are 500 nanoliters each. The depth of the surface channel  100  cannot exceed the width of the surface channel  100 . The maximum depth of the surface channel  100  is equal to the width of the surface channel  100 . It will appreciated that, in other embodiments of the present invention, SALT devices may have different dimensions.  
         [0064]     The liquid  70  may contain treatment agents for processing a particular area of the surface  80 . Engaging the device with the surface  80  causes the treatment agent to flow over the region of the surface  80  facing the flow path  40  from the first port  20  to the second port  30 . The region of the surface  80  facing the flow path  40  is thus exposed to the treatment agents.  
         [0065]     The process herein before described with reference to FIGS.  1  to  5  can be repeated multiple times to treat different regions of the surface  100  or different surfaces. The flow of liquid  70  restarts each time the device engages the surface  80  and stops each time the device is disengaged from the surface  80 . The supply of liquid  70  can be replenished as necessary via the first port  20 .  
         [0066]     The aforementioned treatment agents may be molecules. SALT devices embodying the present invention are thus useful in the bio-patterning of surfaces. However, SALT devices embodying the present invention are not limited in application to delivery of molecules or the like to defined regions of a surface. Other types of liquid may be employed depending on the surface processing desired. SALT devices may be employed to sequentially deliver different treatments to a defined region of a surface. Examples of possible liquids include etchants and the like for producing localized chemical reactions on a surface. Such SALT devices may be reused repetitively, replenishing the supply of liquid as necessary. Process parameters associated with the treatment of the surface can be controlled via pressure difference, liquid viscosity, dimensions of the openings  50  and  60 , surface channel dimensions, and contact time.  
         [0067]     Referring to  FIG. 6 , in a preferred embodiment of the present invention, a first flow controller  130  is provided in the first port  20 . In operation, the first flow controller  190  assists in establishing P 1 . The first flow controller may have many forms. However, in a particularly preferred embodiment of the present invention, the first flow controller  190  comprises a plurality of a capillary members extending into the first port  20 . In operation, the capillary members form a capillary network contributing to P 1  by exerting capillary action on the liquid  70 .  
         [0068]     A second flow controller, similar in form to the first flow controller  190 , is likewise provided in the second port  30 . In operation, the second flow controller assists in establishing P 2 . The second flow controller may have many forms. However, in a particularly preferred embodiment of the present invention, the second flow controller also comprises a plurality of capillary members extending into the second port  30 . The aforementioned capillary members may have circular, hexagonal, square, or rectangular cross sections. Other cross sectional shapes are equally possible.  
         [0069]     In embodiments of the present invention herein before described, the first and second flow controllers each comprise capillary members. However, in other embodiments of the present invention, the first and second flow controllers may each comprise a different form of capillary network, such as a network formed from mesh, porous, or fibrous material. Vacuum pumps may be alternatively employed to develop either or both of P 1  and P 2  in the first port  20  and the second port  30  respectively. Pumps can also permit interactive tuning of the flow of liquid  70  in singular SALT devices or in arrays of SALT devices collectively, individually, or in groups. However, such pumps add complexity to the device.  
         [0070]     In a preferred embodiment of the present invention, the direction of flow of the liquid  70  can be selectively reversed by selectively reversing the pressure difference between the first port  20  and the second port  30 . Specifically, the P 1  can be selectively made greater in magnitude than P 2 . This can be achieved by, for example, selectively increasing the density of capillary members in the first port  20  by adding additional capillary members or by compressing the first port  20 . Alternatively, where P 1  and P 2  are generated via pumps, the pump pressures can be selectively reversed. Other techniques for reversing the pressure difference between the first port  20  and the second port  30  will be apparent to those skilled in the art.  
         [0071]     In the preferred embodiments of the present invention herein before described, there is a single first port  20  and a single second port  30 . However, referring to  FIG. 7 , in other embodiments of the present invention, there may be multiple first ports  160 - 170  coupled to a single second port  30  via a common flow path  40 . Different reactive agents may introduced to each of the first ports  160 - 170  for reaction within the flow path. The flow path  40  may thus act as a reaction chamber activated by proximity of the surface  80 . Similarly, there may be a single first port  20  coupled to multiple second ports via a common flow path  40 . Equally, there may be multiple first ports coupled to multiple second ports via a common flow path  40 .  
         [0072]     Referring to  FIG. 8 , in a particularly preferred embodiment of the present invention, the flow path  40  has a curved cross section to prevent unwanted liquid retention, and residual flows between the first port  20  and the second port  30 .  
         [0073]     With reference to  FIG. 9 , in another preferred embodiment of the present invention, the flow path  40  has a rectangular cross section. This may lead to residual flow along corners of the flow path  40  when separated from the surface  80 . Such residual flows may prevent concentration of reagents by evaporation of the liquid  70  from the opening  50 . The capillary pressure of the flow path  40  when remote from the surface  80  can be optimized by tuning wettability and geometry together with P 1  and P 2  to prevent unwanted liquid retention and to limit the residual flow to a desired value.  
         [0074]     Referring now to  FIG. 10 , in a modification of the preferred embodiment of the present invention herein before described with reference to  FIG. 1 , the flow path  40  is bounded by a peripheral flange  180 . In operation, the flange  180  seals to the surface to further prevent the liquid spreading from the flow path  40 . The flange  180  also serves to define the thickness of the surface channel  100  formed when the device is engaged with the surface  80 . The interior of the flange  180  may be wettable to facilitate contact between the liquid  70  in the first opening  50  and the surface  80  an thus to initiate flow of the liquid  70  between the first port  20  and the second port  30 . In such circumstances, the flange  180  performs the function performed by the protrusion  90  in the  FIG. 1  embodiment. The protrusion  90  may thus be retained or omitted from the  FIG. 9  embodiment. Alternatively, the flange  180  may be held at a small distance from the surface  80  once flow is established for example.  
         [0075]     In the preferred embodiments of the present invention herein before described, features defining the surface channel  100 , such as the protrusion  90  and the flange  180  are integrated into the device. It will be appreciated however that, in other embodiments of the present invention, features defining the surface channel  100  may be provided by formations of the surface  80 .  
         [0076]     With reference to  FIGS. 11 and 12  in combination, in a preferred embodiment of the present invention, a device as herein before described may be aligned with a surface  80  patterned with more wettable areas  81  surrounded by less wettable areas  85 - 88 . The flow path  40  and the more wettable area  81  are matched in size and aligned with each other to define the surface channel  100 . The less wettable areas  85 - 88  help confine the liquid  70  in the surface channel  100 , which is the region perpendicular to the flow path  40 . It will be appreciated that defining the surface channel  100  by more wettable areas  81  that match and can be aligned with the flow path  40  increases flexibility in design of the device and relaxes constraints of the level of wettability contrast.  
         [0077]     In the preferred embodiments of the present invention herein before described, flow initialization is effected by the protrusion  90  or by the flange  180 . However, in other embodiments of the present invention, flow of the liquid  70  along the flow path  40  may be initialized by other techniques. For example, in another embodiment of the present invention, the device has no protrusion  90  or flange  180  adjacent the first opening  40 . To initialize flow of the liquid  70 , the base of the device is first brought into contact with the surface  80  so that the liquid  70  in the first opening contacts and wets the surface  80 . The device is then withdrawn from the surface to a distance equal to the desired depth of the surface channel  100 . Capillary pressure in the surface channel  100  then transports liquid from the first port  20  to the second port  30  until the liquid reaches the second port  30 , whereupon the pressure difference between the first port  20  and second port  30  maintains the flow.  
         [0078]     Referring to  FIG. 13 , this technique is particularly useful for flowing the liquid over a raised area of the surface  80 .  
         [0079]     Referring to  FIGS. 14 and 15  in combination, in this embodiment of the present invention, the side walls  220 - 230  and  260 - 280  of the raised area and the surrounding region  240 - 250  of the surface  80  are non-wettable by the liquid  70 . Thus, the raised area of the surface channel  80  together with the flow path  40  of the device define the surface channel  100 . It will be appreciated that a protrusion may be provided on the raised area of the surface  80  to help initiate flow. Comparing this embodiment of the present invention with that herein before described with reference to  FIG. 1 , it will be appreciated defining the surface channel via a raised area of the surface increases flexibility in design of the device.  
         [0080]     With reference now to  FIG. 16 , in a preferred embodiment of the present invention, the first port  20  and/or second port  30  of the device may be loaded and/or unloaded with the liquid  70  from below via the openings  50  and  60 . Lids may be provided to close the first port  20  and the second port  30 . The lids may be permanently sealed so that liquid can be introduced to the device via the openings  50  and  60  alone. The openings  50  and  60  may likewise be provided with lids to prevent evaporation during periods of nonuse. A reservoir device  510  comprising a reservoir  520  for the liquid  70  may be provided for filling, refilling, and draining the applicator device. The reservoir device facilitates loading and unloading of the first port  20  and the second port  30  of the applicator device independently without requiring removal of the lid. In operation, the reservoir device  510  forms a flow path  101  between the reservoir  520  and the first port  20  or the second port  30  depending on location of the reservoir device  510  relative to the applicator device.  
         [0081]     Embodiments of the present invention have been described herein with reference to a SALT applicator device having less wettable and more wettable surfaces. The initiation and confinement of the flow of the liquid  70  is achieved and controlled via synchronization of pressures exerted on the liquid  70  at different locations, such as in the first and second ports  20 - 30 , in the opening  50 - 60 , and along the flow path  40 . The confinement of the liquid  70  by interfacial tension is a function of surface wettability and geometrical parameters in combination. The confinement pressure involved can be achieved by only a small wettability difference between faces of the device, or, in some cases, with zero wettability difference. This is possible because the geometry of the device and/or surface can be employed to confine the liquid  70 . Preferable confinement conditions can be obtained by superposing a wettability pattern on top of the geometry. The confinement conditions can be calculated analytically by taking into account contact angles of the liquid  70  with the faces, surface tension in the liquid, pressures and flow rates.  
         [0082]     In another embodiment of the present invention, flow initialization is achieved by located the device proximal to the surface  80  in a humid environment. In this arrangement, the device and/or the surface may be initially cooled down to promote condensation, thereby further stimulating flow. Alternatively, an electric field may be applied between the device and the surface in the interests of stimulating the liquid  70  in the first opening  50  to contact the surface  80 . Similarly, a pressure pulse may be applied to the liquid  70  in the first opening  50  likewise to stimulate contact with the surface  80 . Alternatively, a heat pulse may be applied to the liquid  70  to initialize the flow of the liquid from the first port  20  to the second port  30  via vaporization of the liquid  70 .  
         [0083]     Preferred embodiments of the present invention have been herein before described with reference to a single SALT device. However, it will be appreciated that many such devices may integrated to form a SALT array. Referring to  FIGS. 17 and 18  for example,  12  such SALT devices may be integrated into a single 3×4 SALT array of devices. It will be appreciated that many different configurations of SALT array are possible, involving different numbers of SALT devices.  
         [0084]     Referring now to  FIG. 19 , in yet another embodiment of the present invention, the ports of several SALT devices  370 - 390  are interconnected t form a cascade of SALT devices. By generating a less negative pressure in port  420  and a most negative pressure in port  432 , liquid flows from port  420  via a first surface channel to port  421 , and from port  421  via an interconnection to port  430 . From port  430 , the liquid flows via a second surface channel to port  431 , and from port  431  the liquid flows via a third surface channel to port  432 . In a particularly preferred embodiment of the present invention, each of the ports  420 - 432  forms a reaction chamber in which the liquid reacts. The product of such reactions may be analyzed in each of the ports  421  and  431  or in the final port  432  on completion of the reaction. Alternatively, the product of such reactions may be analyzed on the surfaces  370 - 390 . In another alternative, the products of such reactions may be used to treat or react with the surfaces  370 - 390 .  
         [0085]     Preferred embodiments of the present invention have been herein before described with reference to a SALT device having a body  10  formed from an elastomeric or rigid material. Such materials can be shaped by well-known microfabrication techniques, such as photolithography, etching, injection molding and the like. Embodiments present invention based on such materials may be of unitary construction However, it will also be appreciated that the present invention may be implemented by an assemblage of multiple parts. For example, embodiments of the present invention may also be of a layered assembly. Each layer may formed from a different material such as elastomer, silicon, SU-8, photoresist, thermoplastics, ceramic, and metal.  
         [0086]     Placement of a device embodying the present invention relative to a surface may be achieved via a manipulator. Such a manipulator may be manually controlled or automatically controlled via a programmable computer or similar electronic control system. Such a manipulator may act upon the device, the surface or both, providing control of in plane and/or out of plane translational and/or rotational motions. Such manipulators may permit an increase in frequency with which one or more applicator devices embodying the present invention may be engaged with a surface concurrently.