Patent Publication Number: US-2009218412-A1

Title: Non-contact dispensing of liquid droplets

Description:
TECHNICAL FIELD 
     The present invention relates generally to the displacement of droplets of liquid from the end of needles, tubes or other liquid transportation media, and is more particularly concerned with the non-contact dispensing of liquid droplets. 
     BACKGROUND OF THE INVENTION 
     The opposing forces of gravity and surface tension determine a droplet&#39;s shape and, in combination with the size of the orifice, the volume of the droplet. Typically, a liquid with high surface tension will remain at an orifice to form a droplet of several microliters before it breaks from the orifice and falls onto a substrate. If there is a requirement to dispense droplets of a volume less than the “free fall” volume, around 3 μl for aqueous media and other liquids that exhibit similar surface tension, one known approach is to use contact dispensing. Contact dispensing involves the process of bringing the droplet and substrate in close proximity so that the droplet touches the substrate and is released from the orifice and preferentially spreads onto the substrate. Hence, to achieve accurate and repeatable contact dispensing it is necessary to use precision actuators to bring the droplet and substrate in close proximity. Any inaccuracy is cumulative and before long results in either physical contact between the tip at the orifice and the substrate, or failure of the droplet to contact the substrate. 
     An alternative to contact dispensing is non-contact dispensing. Various non-contact dispensing means exist including pressure-dependent solenoid-activated valves (for example the Lee Co.&#39;s miniature solenoid valves and Innovadyne&#39;s low volume pipetting technology), a piezoelectric activated drop-on-demand ink-jet dispenser (for example MicroFab Technologies), aerosol dispensing (Bio-Dot&#39;s Air Jet Quanti) and charged electrostatic dissociation. There is also a known system in which a set volume of liquid is blown out of a capillary by an air pulse in the capillary. 
     In another system, described in U.S. Pat. No. 6,270,019, a sheath of pressurised air directed from an annular opening about the droplet orifice surrounds the dispensed droplet during its flight to an adjacent substrate. The principal purpose of this air sheath is to contain satellite portions that break away from the droplet within the discharged sheath to prevent them from falling onto areas of the substrate outside the desired zone, a problem that commonly arises in the absence of the sheath. 
     The choice of which non-contact dispensing means to use is influenced by what features are required for droplet displacement—for example the volume of the droplet, the density of droplets in an array, the speed of droplet dispensing. 
     Most of the non-contact dispensing systems are fully integrated and dedicated automated systems requiring significant capital expenditure and training of personnel for their routine operation. There is a need in the market for a simplified device that preferably can be adapted for addition to a typical contact dispensing system to offer the user a non-contact dispensing mode. 
     It is an object of the invention to provide an improved apparatus and method to carry out non-contact dispensing of liquid droplets. 
     DISCLOSURE OF THE INVENTION 
     The present invention provides for the dispensing of droplets from an orifice by means of a shock wave that displaces the droplet from the orifice, without any requirement for the droplet to contact a substrate prior to its displacement from the orifice. 
     The present invention provides, in a first aspect, apparatus for dispensing droplets of a liquid that comprises structure providing a passage along which the liquid may be delivered to form a droplet at an orifice. The structure is configured to propagate a shockwave to impact the droplet and thereby to displace the droplet from the orifice, whereby the droplet is dispensed. 
     In a second aspect, the invention provides apparatus for dispensing droplets of a liquid that comprises structure providing an elongate passage to longitudinally receive a syringe needle positionable with its tip, and the orifice at the tip, at or adjacent on open end of the passage. One or more needle guides locate the needle in the passage, which is of greater cross-section than the needle at the open end. A seal arrangement substantially seals the passage about the needle at a position displaced from the open end of the passage, whereby to define a chamber between that position and the open end. The apparatus is configured to deliver to the chamber a shockwave that is propagated from the chamber at the open end to impact a droplet of the liquid at the orifice and thereby to displace the droplet from the orifice, whereby the droplet is dispensed. 
     In a third aspect, the invention provides a method for dispensing a droplet of a liquid, including:
         delivering the liquid along a passage to form a droplet at an orifice that opens from the passage; and   generating a shockwave and propagating it to impact said droplet and thereby displace it from the orifice, whereby the droplet is dispensed.       

     In a fourth aspect, the invention provides apparatus for dispensing droplets of liquid, including a syringe drive device, having a head adapted to be coupled to a syringe and means to operate the syringe to dispense droplets by free-fall from the syringe tip orifice, and structure adapted to be selectively coupled to the head and/or to a syringe carried thereby. The structure is configured to propagate a shockwave to impact a droplet at the orifice that is too small to freefall, and thereby to displace the droplet from the orifice, whereby the droplet is dispensed. 
     Preferably, the shockwave is a pulse of a gas, most conveniently a pulse of air. 
     Preferably, the pulse is propagated to impact the droplet from adjacent the orifice so that the droplet is displaced in a direction directly away from the orifice. In an embodiment, the shockwave is arranged to displace the droplet in a direction generally along the axis of the passage. Typically in use, this axis will be generally vertical so that the orifice is at the lower end of the passage and/or syringe needle. 
     In a practical embodiment, the syringe drive device has a motorised drive for aspirating and dispensing liquid at said orifice. 
     Advantageously, the surface of the passage and/or syringe needle is treated adjacent the orifice to facilitate droplets forming at the orifice. 
     The volume of each droplet is preferably in the range 5 nanoliters to 5 microliters. A droplet size of particular interest is around 50 nanoliters. 
     Means is preferably provided to generate the shockwave and to deliver it to said structure. This means may typically include a solenoid drive and a controller which allows selective modification of the solenoid operation and thereby of the form of the shockwave. 
     To maintain integrity of the droplet shape, the droplet is typically displaced within a distance of 0.5 mm to 5 mm of the substrate. The shockwave air pulse generation system is preferably configured to allow a sufficient impact force to be applied with a minimal amount of turbulence resulting in the vicinity of the droplet landing area. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention will now be further described, by way of example only, with reference to the accompanying drawings, in which: 
         FIG. 1  is a schematic view of a syringe drive device in which the syringe is coupled to an embodiment of apparatus for the non-contact dispensing of droplets in accordance with the concepts of the present invention; 
         FIG. 2  is an axial cross section of the droplet dispensing apparatus depicted in  FIG. 1 ; 
         FIG. 3  is a view similar to  FIG. 2 , but with the needle in situ; and 
         FIG. 4  is an axial cross section of the shockwave generator for generating a shockwave to displace the droplet from the dispensing orifice in the arrangement depicted in  FIG. 1 . 
     
    
    
     EMBODIMENTS OF THE INVENTION 
     The syringe drive device  10  schematically shown in  FIG. 1 , which may, for example, be a multi-axis auto sampler, includes a carriage  100  translatable (by means not detailed) in all three X, Y and Z dimensions for selectively picking up syringes  200  from a syringe stand  700 , and then, by means of the drive  150 , operating the picked up syringe to aspirate sample liquid at one station and then dispense droplets at another station. The dispensing station is represented by a substrate  600  with multiple sample recesses  602  in which a droplet of the sample liquid is deposited in turn. Where the required droplet size is greater than the freefall volume, typically about 3 μl for aqueous media and other liquids having a similar surface tension, droplets can be dispensed directly by freefall from the orifice at the tip  205  of the needle  202 . 
     For the purpose of dispensing smaller droplets, there is provided a non-contact dispenser device  400  that comprises an embodiment of apparatus incorporating concepts of the present invention. Non-contact dispenser device  400  is also designed to be held at the syringe stand  700  and to be picked up by syringe drive device  100  by being coupled to the lower end of syringe  200  and then moved into position at the dispensing station above substrate  600 , as illustrated in  FIG. 1 . 
     Associated with non-contact dispenser device  400  is a shockwave generator  300  which is mounted on the translator carriage  100  and is operable by a controller to deliver shockwaves in the form of pulses of air to device  400  via an air tube or other communication means  500 . 
     In a typical operation, syringe drive  150  will be operated to pick up, from syringe stand  700 , a syringe  200  of known volume per known stroke length, and then to displace the syringe to a sample vial (not shown). Syringe drive  150  is then operated to drive the syringe needle tip, including an orifice at the tip, through septa into the vial, after which the syringe plunger is driven to aspirate the desired volume of sample into syringe  200  via the orifice in needle  202 . The syringe needle is then withdrawn from the sample vial via the septa which wipes any sample from the orifice. The translator system now moves the syringe drive and the syringe  200  to pick up a non-contact dispenser device  400  from syringe holder  700  and the air line  500  is connected to the dispenser ready for dispensing of droplets onto substrate  600 . 
     With particular reference to  FIG. 2 , non-contact dispenser device  400  has an elongate generally cylindrical barrel  410  with an axially extending passage  412  that opens at both ends of the barrel. In the case of the lower end, the open end  415  of the passage is in a flat face forming the tip  403  of a conical end portion  413  of barrel  410 . Passage  412  is dimensioned to receive needle  202  of syringe  200  such that there is some space about the needle ( FIG. 3 ), and in particular passage  412  is of greater cross-section than the needle at open end  415 . This needle is located, indeed centered, in passage  412 , and in the open bottom end  415  of the passage, by a pair of axially spaced O-rings  402  that serve as needle guides. O-rings  402  are accommodated in cavities  417  formed by dividing barrel  410  into three interlocking segments  420 ,  425 ,  430 , as illustrated in  FIG. 2 . 
     A counterbore enlargement of passage  412  in tip barrel segment  420  forms a co-axial, axially symmetrical plenum chamber  422  to which air pulses are delivered via communication line  500  and a fixed tube  404  that opens radially into chamber  422  at its rear end. O-ring  402  at the lower end forms a seal arrangement to substantially seal passage  412  about the needle at a position displaced from open end  415 , whereby to define plenum chamber  422  between this position and open end  415 . 
     For easy coupling to dispenser device  400 , the syringe  200  is fitted with a connector  407  having a threaded socket  406  by which it is mounted to the outer end of the syringe barrel. A male part  434  of connector  407  engages a mating socket  432  on the rearmost barrel segment  430  of dispenser  400 . Disengagable coupling of the parts is latched by a spring clip  405  on barrel segment  430 . It can be seen from  FIG. 2  that the male part  434  of connector  407  includes a central bore  436  aligned with passage  412 . 
     Shockwave generator  300  is a solenoid actuated device and is illustrated in detail in  FIG. 4 . A 12-volt solenoid  306  axially drives a plunger  307  that is coupled in turn to a push rod  308 . The tip of push rod  308  internally engages piston  304  but is not actively connected to the piston. Piston  304  is in turn slideable within a cylinder  302  but biased outwardly and upwardly in the cylinder chamber  310  by a light helical compression spring  301 . The piston  304  is sealed to the chamber wall by a labyrinth seal  305 , while chamber  310  has an outlet passage  312  co-axial with the chamber and opposite the piston. The outlet passage  312  has a relatively small cross section, leading to a tip  303  of the cylinder at which passage  312  is connected to communication line  500 . 
     Shockwave generator  300  outputs air pulses at tip  303  as follows. A controller (not shown) transmits 12-volt pulses to solenoid  306 . The consequent rapid movement of the push rod  308  forces piston  304  sharply to the end of cylinder chamber  310 . The speed with which the piston travels, in conjunction with the labyrinth seal  305 , causes a rapid rise in pressure in chamber  310 . This pressure generates a shockwave in the form of a pulse of air that exits the generator at the tip  303  and travels down the communication line  500  to plenum chamber  422  of dispenser  400 . The piston  304  is held against the end of chamber  310  for the duration of the solenoid activation pulse. When the pulse ceases, the piston returns to its original position due to the minimal force applied by the return spring  301 . 
     The operation of dispenser  400  will now be described in greater detail. Once the syringe drive with its coupled syringe  200  and dispenser  400  is in the correct position over substrate  600 , the aforementioned controller sends signals to syringe drive  150  to move the syringe plunger a known length to displace a known volume of sample from the orifice  800  of the needle  202 , which forms a droplet  900  ( FIG. 1 ) at orifice  800  just below the end  415  of passage  412 . Typically, this volume is less than the freefall volume, for example 50 to 100 nanoliters, and so the droplet  900  is retained by surface tension effects on the exterior of the orifice. 
     The controller now sends the aforementioned pulse signal to the solenoid  306  of the shockwave generator  300 , and an air pulse shockwave is delivered to plenum chamber  422 . The shockwave is propagated about the needle along passage  412  to impact the droplet  900  ( FIG. 1 ) on the end of the needle. By selective operation of piston  304 , the shockwave is arranged to be sufficient to displace the droplet from the orifice, and to thereby dispense it onto substrate  600 , but with an impact force such that no satellites form from the droplet and there is substantially no fragmentation of the droplet. Moreover, it is desirable that the air pulse is such that there is no or very little turbulence in the vicinity of the droplet landing area. 
     It may be advantageous, depending on the liquid being dispensed, to treat the surface of the needle  202  adjacent its orifice  800  to create the correct environment for droplet formation. Typically, this treatment might involve polysiloxane chemistry to prepare the surface for creating the preferred contact angle between the liquid and the surface. 
     It has been found that the illustrated apparatus is capable of dispensing droplets of the order of 50 to 70 nanoliters at high repetition rates with high volume accuracy and no or minimal droplet fragmentation. Displacement of droplets as small as 5 to 10 nanoliters is thought to be achievable.