Systems and methods for high speed array printing and hybridization

Abstract

Novel and improved systems and methods for high speed arraying, hybridization, quantitative development and/or assaying are provided. Some embodiments provide a web based arraying format. Some other embodiments provide a sheet based arraying format. Some embodiments use a drop on drop assaying or hybridization mode. In some embodiments, a substantially inert substrate is utilized. In some other embodiments, an interactive substrate is utilized.

1 . A high speed array manufacturing system, comprising:
 a dispense module comprising a plurality of non-contact dispensers arranged in a predetermined configuration with a predetermined spacing for dispensing reagent drops onto a substrate medium;   a controller for providing relative motion between said dispensers and said substrate medium on which an array is formed to manufacture a substrate structure for assaying;   said array having reagent spots dispensed on said substrate medium with spacings that are less than the spacings between said dispensers to form a high density substrate structure.   
   
   
       2 . The system of  claim 1 , wherein said drops have a volume in the range from about 100 picoliters or less to about 1 microliter. 
   
   
       3 . The system of  claim 2 , wherein said drops have a volume in the range from about 20 picoliters to about 1 microliter. 
   
   
       4 . The system of  claim 1 , wherein said spots have a size in the range from about 50 microns to about 1 mm or greater. 
   
   
       5 . The system of  claim 1 , wherein said dispensers comprise solenoid actuated or piezo dispensers. 
   
   
       6 . The system of  claim 1 , wherein said substrate medium comprises an inert or passive substrate. 
   
   
       7 . The system of  claim 1 , wherein said substrate medium comprises an interactive or active substrate. 
   
   
       8 . The system of  claim 1 , wherein said substrate medium comprises a glass slide or a membrane. 
   
   
       9 . The system of  claim 1 , wherein said substrate medium comprises a film and said substrate structure comprises said film and a carrier arranged in a web format. 
   
   
       10 . The system of  claim 1 , wherein said substrate medium comprises a sheet format. 
   
   
       11 . The system of  claim 1 , wherein said dispense module comprises a motion positioner. 
   
   
       12 . The system of  claim 1 , wherein said system further comprises a laminate module. 
   
   
       13 . The system of  claim 1 , wherein said system further comprises a drying module. 
   
   
       14 . The system of  claim 1 , wherein said system further comprises a capstan module. 
   
   
       15 . The system of  claim 1 , wherein said system further comprises a take-up module. 
   
   
       16 . The system of  claim 1 , wherein said system further comprises a blocker spray or dip module immediately downstream of said dispense module. 
   
   
       17 . The system of  claim 1 , wherein said assaying comprises hybridization. 
   
   
       18 . A high speed assaying system, comprising:
 a dispense module comprising a dispense head and a motion positioner;   said dispense head comprising a plurality of non-contact dispensers arranged in a predetermined configuration with a predetermined spacing for dispensing reagent drops onto an array substrate with target spots formed thereon or therein such that said drops are precisely delivered at the position of the selected target spots;   a controller to monitor and control said dispensers and relative motion between said dispensers and said array substrate.   
   
   
       19 . The system of  claim 18 , wherein said dispensers comprise solenoid actuated or piezo dispensers. 
   
   
       20 . The system of  claim 18 , wherein said array substrate comprises an inert or passive substrate. 
   
   
       21 . The system of  claim 18 , wherein said substrate medium comprises an interactive or active substrate. 
   
   
       22 . The system of  claim 18 , wherein said array substrate comprises a glass slide or a membrane. 
   
   
       23 . The system of  claim 18 , wherein said array substrate comprises a film and a carrier arranged in a web format. 
   
   
       24 . The system of  claim 18 , wherein said array substrate medium comprises a sheet format. 
   
   
       25 . The system of  claim 18 , wherein said system further comprises at least one tandem motion system to achieve high throughput and substantially continuous operation. 
   
   
       26 . The system of  claim 18 , wherein said drops are dispensed at a velocity and/or momentum to provide enhanced mixing and/or reaction kinetics with the selected array spot. 
   
   
       27 . The system of  claim 18 , wherein said system further comprises a payout module. 
   
   
       28 . The system of  claim 18 , wherein said system further comprises a vision module. 
   
   
       29 . The system of  claim 18 , wherein said system further comprises an incubation module. 
   
   
       30 . The system of  claim 18 , wherein said system further comprises a reader module. 
   
   
       31 . The system of  claim 18 , wherein said system further comprises a take-up module. 
   
   
       32 . The system of  claim 18 , wherein said system further comprises an incubation module and a reader module, and wherein said system further comprises a blocker spray or dip module intermediate said incubation and reader modules. 
   
   
       33 . The system of  claim 30 , wherein said reader module comprises an optical detection device. 
   
   
       34 . The system of  claim 33 , wherein said optical detection device comprises a chemoluminescence, fluorescence, and/or absorption device. 
   
   
       35 . The system of  claim 18 , wherein said system further comprises a sample storage machine to store sample plates. 
   
   
       36 . The system of  claim 35 , wherein said sample plates comprise identifiers. 
   
   
       37 . The system of  claim 36 , wherein said identifiers comprise barcode, punch card, and/or Radio Frequency Identification Device (RFID) identifiers. 
   
   
       38 . The system of  claim 18 , wherein said assaying comprises hybridization. 
   
   
       39 . The system of  claim 18 , wherein said assaying comprises PCR assaying and said substrate comprises a PCR plate. 
   
   
       40 . The system of  claim 39 , wherein said spots comprise at least one oligonucleotide. 
   
   
       41 . The system of  claim 40 , wherein said oligonucleotide comprises a TaqMan® probe. 
   
   
       42 . The system of  claim 39 , wherein said reagent drops are dispensed through a layer of oil covering said spots. 
   
   
       43 . The system of  claim 42 , wherein said reagent drops comprise a sample and/or a master mix. 
   
   
       44 . The system of  claim 43 , wherein said system further comprises a thermal cycling module to process said PCR plate. 
   
   
       45 . The system of  claim 44 , wherein said system further comprises a read module downstream of said thermal cycling module. 
   
   
       46 . The system of  claim 18  in combination with the system of  claim 1  to form a array manufacturing and assaying system.