Abstract:
A method of washing an array of pipette tips ( 94 ) with residual biological material includes lowering the array of pipette tips ( 94 ) into a wash basin ( 20 ) that includes an array of flush ports ( 22 ). A vacuum is generated such that the residual biological material in the array of pipette tips ( 94 ) is evacuated through the array of flush ports ( 22 ). A wash cycle is performed that includes raising the array of pipette tips ( 94 ) from the wash basin ( 20 ), filling the wash basin ( 20 ) with a primary wash fluid, lowering the array of pipette tips ( 94 ) into the wash basin ( 20 ), miming a pipette tip cleansing cycle, and generating a vacuum such that the primary wash fluid in the array of pipette tips ( 94 ) and the wash basin ( 20 ) is evacuated through the array of flush ports ( 22 ).

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
       [0001]    This application claims priority from U.S. Provisional Application No. 61/818,099, filed May 1, 2013 for “PIPETTE WASH” by Chad Steven Smith et al. 
     
    
     BACKGROUND 
       [0002]    The present invention relates to inline sample processing on Douglas Scientific&#39;s Nexar® platform, and more specifically relates to a pipette wash for a dispensing system. 
         [0003]    Advances in the biosciences industry have created a demand for high throughput biological sample processing and detection systems. For example, Astle, U.S. Pat. No. 6,632,653, discloses a high throughput method of performing biological assays using a tape with a matrix of wells. In a high throughput system, the source and assay are transferred from microplates into the tape, the tape is sealed, and the tape is accumulated on spools. The tape containing samples, such as biological samples, is then transferred to a water bath product and a reaction may be performed, such as polymerase chain reaction (PCR) using thermocycling. Subsequently, the tape may be loaded onto a detection instrument, which detects presence of a desired analyte, such as nucleic acid presence in a biological sample. 
         [0004]    Pipette tips for sample dispensing in such high throughput systems are commonly used once to transfer a biological sample into the tape wells due to the risk of cross contamination associated with reusing pipette tips. Consumable materials like pipette tips increase costs associated with high throughput systems due to the cost of the pipette tips and waste disposal. With a push towards increasing reaction speeds to process even more samples at an ever faster rate, pipette tip costs could become prohibitively expensive. 
       SUMMARY 
       [0005]    A method of washing an array of pipette tips with residual biological material includes lowering the array of pipette tips into a wash basin that includes an array of flush ports. A vacuum is generated such that the residual biological material in the array of pipette tips is evacuated through the array of flush ports. A wash cycle is performed that includes raising the array of pipette tips from the wash basin, filling the wash basin with a primary wash fluid, lowering the array of pipette tips into the wash basin, running a pipette tip cleansing cycle, and generating a vacuum such that the primary wash fluid in the array of pipette tips and the wash basin is evacuated through the array of flush ports. 
         [0006]    In another embodiment, a system for washing an array of pipette tips with residual biological material includes a wash basin with an array of flush ports for receiving the array of pipette tips, a primary pump for filling the wash basin with a primary wash fluid, and a vacuum generator for generating a vacuum such that the primary wash fluid and residual biological material in the array of pipette tips and the wash basin is evacuated through the array of flush ports. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0007]      FIG. 1  is a partial perspective and partial exploded view of a pipette wash system. 
           [0008]      FIG. 2  is an exploded view of the pipette wash sub assembly of the pipette wash system of  FIG. 1 . 
           [0009]      FIG. 3  is a perspective view of the pipette wash sub assembly of the pipette wash system of  FIG. 1  and a dispensing jet system. 
           [0010]      FIG. 4A  is a top view of the pipette wash sub assembly of  FIG. 3  with vacuum ports. 
           [0011]      FIG. 4B  is a cross-sectional view of the pipette wash subassembly of  FIG. 4A  along line  4 B- 4 B. 
           [0012]      FIG. 5A  is a top view of the pipette wash sub assembly of  FIG. 3  with a vacuum halo. 
           [0013]      FIG. 5B  is a cross-sectional view of the pipette wash subassembly of  FIG. 5A  along line  5 B- 5 B. 
           [0014]      FIG. 6A  is a top view of the pipette wash sub assembly of  FIG. 3  with a vacuum shroud. 
           [0015]      FIG. 6B  is a cross-sectional view of the pipette wash subassembly of  FIG. 6A  along line  6 B- 6 B. 
       
    
    
     DETAILED DESCRIPTION 
       [0016]    The present disclosure includes a fully automated pipette wash that provides tip cleaning functionality to a dispensing system, allowing pipette tips to be reused with minimal cross contamination. A dispensing system is used to aspirate samples from sample plates and dispense samples into a tape with a matrix of wells. To ensure that the desired amount of biological sample is dispensed into the tape, the dispensing system aspirates more sample than necessary. When the sample is dispensed into the tape, residual sample material, including the volume overage, remains in the pipette tips of the dispensing system. When pipette tips are reused, the pipette wash reduces the potential for residual material from a previous dispensing cycle to be deposited into the tape in a later dispensing cycle. 
         [0017]      FIG. 1  is a partial perspective and partial exploded view of pipette wash system  10 . Pipette wash system  10  includes pipette wash sub assembly  12  with pump  14 , wash fluid check valve  16 , venturi adapter  18 , and discrete tip wash basin  20  with flush array  22 . Pipette wash system  10  further includes vacuum pump  24  with air line fitting  26 , valve bracket  28  with valve  30  and fasteners  32 , wash mounting plate  34 , electrical enclosure  36  with cable/cord port  38 , air cylinder valve/fitting assembly  40 , vacuum pump valve  42 , pump  44 , wash fluid fittings  46  and  48 , carboy  50 , and jug  52 . 
         [0018]    Valve  30  is mounted to valve bracket  28 , and fasteners  32  attach valve bracket  28  to mounting plate  34 . Electrical enclosure  36  with cable/cord port  38  is mounted on mounting plate  34  and contains all of the electronics to control pipette wash system  10 . Air cylinder valve/fitting assembly  40  is attached to electrical enclosure  36 . Vacuum pump valve  42  is mounted to mounting plate  34  and turns vacuum pump  24  on and off. Vacuum pump  24  passes through an opening in mounting plate  34  and connects pipette wash sub assembly  12  to carboy  50 . Air line fitting  26  connects an air line to vacuum pump  24 . Pump  44  and pipette wash sub assembly  12  are also mounted on wash mounting plate  34 . Wash fluid fittings  46  and  48  connect wash fluid lines to pump  44 . 
         [0019]    Pipette wash sub assembly  12  is the portion of pipette wash system  10  that comes into contact with pipette tips from a dispensing system in order to clean the pipette tips. Pipette wash sub assembly  12  includes discrete tip wash basin  20 , which may be, for example, made of noryl or any other suitable material that is well suited for alkalines and acids. In an alternative embodiment, discrete tip wash basin  20  may be, for example, made of a clear material that allows ultraviolet light to travel through discrete tip wash basin  20  to treat pipette tips as they are lowered into discrete tip wash basin  20 . Discrete tip wash basin  20  includes flush array  22 , an array of ports for evacuating liquid and biological waste during operation of pipette wash system  10 . Flush array  22  may include an array of 384 ports, for example. In an alternative embodiment, flush array  22  may include an array of 96 ports. 
         [0020]    Pump  44  pumps a wash fluid, such as a cleaning solution of bleach containing 6% sodium hypochlorite, for example, from jug  52 , through wash fluid check valve  16 , and into discrete tip wash basin  20  to flood discrete tip wash basin  20 . Pump  44  pumps a wash fluid, such as water, for example, through wash fluid check valve  16  into discrete tip wash basin  20 . 
         [0021]    Discrete tip wash basin  20  is designed to work with vacuum pump  24  to create a discrete vacuum on each pipette tip of a dispensing system, subsequently maximize the suction effect around each pipette tip, and finally reduce or eliminate any remaining or residual wash fluid. Venturi adapter  18  receives vacuum pump  24 , which is a material conveying pump that provides a large volume of air flow to pipette wash sub assembly  12  in order to provide a uniform vacuum for evacuating material from discrete tip wash basin  20  through flush array  22 . Vacuum pump  24  is configured to provide a uniform vacuum such that there is a vacuum draw on every open port of flush array  22 . If the pressure is right and the draw is thorough from vacuum pump  24 , flush array  22  may be an array of any number of ports. In one embodiment, flush array  22  may include a single (one) port. In an alternative embodiment, flush array  22  may include 96 ports. In an alternative embodiment, flush array  22  may include 384 ports. Carboy  50  receives material evacuated from discrete tip wash basin  20  through flush array  22 . 
         [0022]      FIG. 2  is an exploded view of pipette wash sub assembly  12 . Pipette wash sub assembly  12  includes venturi adapter  18 , discrete tip wash basin  20  with flush array  22 , screw set  54 , drain hose fittings  55 , wash stands  56 , wash tub  58 , fasteners  60 , wash fluid hose fittings  62 , air cylinder  64 , air cylinder fittings  66 , fasteners  68 , wash base  70 , washers  72 , wash valve plate  74 , mount block  76 , fastener  78 , mount spacer  80 , fasteners  82 , wash jets  84 , washers  86 , and fasteners  88 . 
         [0023]    Wash stands  56  are connected to wash tub  58  with fasteners  60 . Wash tub  58  holds wash base  70 , wash valve plate  74 , and discrete tip wash basin  20 . Wash fluid hose fittings connect wash fluid supplies to wash tub  58 . Wash jets  84  port wash fluid into discrete tip wash basin  20 . Discrete tip wash basin  20  stacks on top of wash valve plate  74 , which stacks on top of wash base  70 . Mount block  76 , fastener  78 , mount spacer  80 , and fasteners  82  connect wash valve plate  74  to air cylinder  64 . Fasteners  68  connect air cylinder  64  to wash tub  58 . Air cylinder fittings  66  connect air cylinder to an air supply. 
         [0024]    Wash valve plate  74  includes an array of valves that line up with the array of ports in flush array  22  of discrete tip wash basin  20 . In one embodiment, wash valve plate  74  may include an array of  384  valves. In another embodiment, wash valve plate  74  may include an array of  96  valves. In another embodiment, wash valve plate  74  may include a single (one) valve. Wash valve plate  74  works with vacuum pump  24  in order to control vacuum timing. Air cylinder valve/fitting assembly  40  turns air cylinder  64  on to shift wash valve plate  74  in order to allow fluid evacuation from discrete tip wash basin  20 . When wash valve plate  74  shifts, all wash fluids are evacuated from discrete tip wash basin  20  within seconds. 
         [0025]      FIG. 3  is a perspective view of pipette wash sub assembly  12  and dispensing jet system  92 . Pipette wash sub assembly  12  includes wash tub  58 , air cylinder  64 , wash jets  84 , and discrete tip wash basin  20  with flush array  22  and fingers  90 . Dispensing jet system  92  includes pipette tips  94 . Pipette tips  94  may be arranged in an array of  384  tips. In an alternative embodiment, pipette tips  94  may be arranged in an array of  96  tips. In an alternative embodiment, pipette tips  94  may include a single (one) pipette tip. The ports of flush array  22  are aligned with pipette tips  94  in order to evacuate material from pipette tips  94 . Fingers  90  of discrete tip wash basin  20  reduce surface area on which wash fluid can sit, allowing effective evacuation of wash fluid through flush array  22 . Fingers  90  form an undulating surface to create a non-planar surface with minimal surface area at any one point. This facilitates fast and complete evacuation of a wash solution from wash basin  20  and reduces the amount of residual wash solution in wash basin  20 . 
         [0026]    Referring now to  FIGS. 1-3 , in a high throughput system dispensing jet system  92  aspirates a predetermined volume of biological material, such as genetic fluid from soy or corn, for example, into each of pipette tips  94  at the same time. The volume aspirated includes a volume overage in order to ensure dispensing accuracy. Upon completion of this aspiration step, dispensing jet system  92  shifts over to an array tape into which dispensing jet system  92  dispenses a predetermined amount of biological material. Dispensing jet system  92  then shifts over to pipette wash system  10  and lowers pipette tips  94  down into discrete tip wash basin  20 , dispensing the remaining biological material while a flush cycle simultaneously begins. Dispensing jet system  92  may, for example, include a vibration system in order to assist in dislodging biological material from pipette tips  94 . 
         [0027]    In the flush cycle, vacuum pump  24  creates a vacuum such that the remaining biological material in pipette tips  94  is evacuated through flush array  22  and wash valve plate  74 , and disposed of in carboy  50 . Dispensing jet system  92  rises while pipette wash system  10  finishes the flush cycle. Pipette wash system  10  then begins a fill cycle by filling discrete tip wash basin  20  with a wash solution. In one embodiment, pump  44  pumps a primary fluid into discrete tip wash basin  20  to fill discrete tip wash basin  20 . Depending on the biological material, a secondary fluid, such as bleach, may be needed to clean pipette tips  94 . Therefore, in an alternative embodiment pump  14  pumps a secondary fluid, such as bleach, for example, into discrete tip wash basin  20  and adds a primary fluid, such as water to obtain a desired percentage of secondary fluid in discrete tip wash basin  20 . During each fill cycle, discrete tip wash basin  20  is filled with approximately 90 mL of water. 
         [0028]    As discrete tip wash basin  20  is filled with the wash solution, dispensing jet system  92  lowers pipette tips  94  back down and begins a series of dispensing pipette piston cycles, aspirating and dispensing the wash solution in pipette tips  94 . In an alternative embodiment, pipette tips  94  may be detachable such that pipette tips  94  are released onto discrete tip wash basin  20  and a secondary head of dispensing system  92  flows wash fluid through pipette tips  94 . The number of dispensing pipette piston cycles may range from 1 to 24 cycles, varying depending on application optimization. 
         [0029]    Once the dispensing pipette piston cycles are complete, vacuum pump  24  creates a vacuum such that the wash solution is evacuated from discrete tip wash basin  20  and pipette tips  94  through flush array  22  and wash valve plate  74 , and disposed of in carboy  50 . Dispensing jet system  92  rises while pipette wash system  10  finishes the flush cycle. The fill and flush cycles make up one complete wash cycle. The wash cycle is repeated until pipette tips  94  are satisfactorily cleaned. The number of wash cycles is typically 3-4 cycles, but may vary from 1-6 cycles depending on application optimization. The entire wash process lasts just over one minute. 
         [0030]    In an alternative embodiment, pipette wash system  10  may include, for example, an ultraviolet light apparatus in discrete tip wash basin  20  to aid in neutralizing biological material from pipette tips  94 . The ultraviolet light apparatus could be a ring light, point light, or another other suitable light apparatus that would aid in neutralizing biological material from pipette tips  94 . In another alternative embodiment, pipette wash system  10  and dispensing system  92  may include a shroud that surrounds the pipette head of pipette tips  94 , pipette tips  94  and discrete tip wash basin  20 . Ultraviolet light may be shone into the shroud in order to assist in neutralizing biological material from pipette tips  94 . 
         [0031]      FIG. 4A  is a top view of pipette wash sub assembly  12 .  FIG. 4B  is a cross-sectional view of pipette wash subassembly  12  along line  4 B- 4 B. Pipette wash sub assembly  12  includes discrete tip wash basin  20  with flush array  22 , wash tub  58 , wash jets  84 , vacuum ports  96 , and wash basin drain ports  97 . Vacuum ports  96  are located within wash tub  58 . Vacuum ports  96  are connected to vacuum source  98 . Vacuum source  98  may be vacuum pump  24 , as shown in  FIGS. 1-3 . Wash basin drain ports  97  are located within discrete tip wash basin  20  and drain excess wash fluid during a wash cycle. During a wash cycle, vapors may form above pipette wash sub assembly  12  due to the presence of chemicals such as sodium hypochlorite in the wash fluid. Vacuum source  98  creates a vacuum to evacuate the vapors through vacuum ports  96 . Vacuum source  98  may be used to evacuate the vapors at any point during or after a wash cycle. 
         [0032]      FIG. 5A  is a top view of pipette wash sub assembly  12 .  FIG. 5B  is a cross-sectional view of pipette wash subassembly  12  along line  5 B- 5 B. Pipette wash sub assembly  12  includes discrete tip wash basin  20  with flush array  22 , wash tub  58 , and air cylinder  64 , and vacuum halo with vacuum ports  102 . Conduit  104  connects vacuum halo  100  to vacuum source  106 . Filter  108  may be inserted in conduit  104 . Vacuum halo  100  is hollow and is located on top of wash tub  58 . During a wash cycle, vapors may form above pipette wash sub assembly  12  due to the presence of chemicals such as sodium hypochlorite in the wash fluid. Vacuum source  106  creates a vacuum to pull the vapors through vacuum ports  102  of vacuum halo  100  into vacuum halo  100  and evacuate the vapors through conduit  104 . Filter  108  filters vapors passing through conduit  104 . Filter  108  may be a coalescing filter. Vacuum source  106  may be used evacuate the vapors at any point during or after a wash cycle. 
         [0033]      FIG. 6A  is a top view of pipette wash sub assembly  12 .  FIG. 6B  is a cross-sectional view of pipette wash subassembly  12  along line  6 B- 6 B. Pipette wash sub assembly  12  includes discrete tip wash basin  20  with flush array  22 , wash tub  58 , and air cylinder  64 , and vacuum shroud  110 . Conduit  112  connects vacuum shroud  110  to vacuum source  114 . Filter  116  may be inserted in conduit  112 . Vacuum shroud  110  is hollow. Vacuum shroud  110  surrounds wash tub  58  and extends above wash tub  58 . During a wash cycle, vapors may form above pipette wash sub assembly  12  due to the presence of chemicals such as sodium hypochlorite in the wash fluid. Vacuum source  114  creates a vacuum to pull the vapors into vacuum shroud  110  and evacuate the vapors through conduit  112 . Filter  116  filters vapors passing through conduit  112 . Filter  116  may be a coalescing filter. Vacuum source  114  may be used to evacuate the vapors at any point during or after a wash cycle. 
         [0034]    While the invention has been described with reference to an exemplary embodiment(s), it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment(s) disclosed, but that the invention will include all embodiments falling within the scope of the appended claims.