Apparatus and method for polymer synthesis using arrays
View Patent ↗A polymer synthesis apparatus ( 20 ) for building a polymer chain including a head assembly ( 21 ) having an array of nozzles ( 22 ) with each nozzle coupled to a reservoir ( 23 ) of liquid reagent ( 24 ), and a base assembly ( 25 ) having an array of reaction wells ( 26 ). A transport mechanism ( 27 ) aligns the reaction wells ( 26 ) and selected nozzles ( 22 ) for deposition of the liquid reagent ( 24 ) into selected reaction wells ( 26 ). A sliding seal ( 30 ) is positioned between the head assembly ( 21 ) and the base assembly ( 25 ) to form a common chamber ( 31 ) enclosing both the reaction well ( 26 ) and the nozzles ( 22 ) therein. A gas inlet ( 70 ) into the common chamber ( 31 ), upstream from the nozzles ( 22 ), and a gas outlet ( 71 ) out of the common chamber ( 31 ), downstream from the nozzles ( 22 ), sweeps the common chamber ( 31 ) of toxic fumes emitted by the reagents. Each reaction well ( 26 ) includes an orifice ( 74 ) extending into the well ( 26 ) which is of a size and dimension to form a capillary liquid seal to retain the reagent solution ( 76 ) in the well ( 26 ) for polymer chain growth therein. A pressure regulating device ( 82 ) is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well ( 26 ) and a second gas pressure exerted on an exit ( 80 ) of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution ( 76 ) is expelled from the well ( 26 ) through the orifice ( 74 ). A method of synthesis of a polymer chain in a synthesis apparatus ( 20 ) is also included.
1. A polymer synthesis apparatus for building a polymer chain by sequentially adding polymer units in a reagent solution, said apparatus comprising:
a head assembly having a plurality of nozzles mounted thereto in generally spaced-apart relation, each nozzle being coupled to a reservoir of liquid reagent for controlled delivery therethrough;
a base assembly having at least one reaction well; a transport mechanism coupled to at least one of said head assembly and said base assembly to produce relative movement therebetween to position said reaction well and a selected one nozzle in alignment for deposition of a liquid reagent into said reaction well for synthesis of a polymer chain; and
a sliding seal positioned between said head assembly and said base assembly forms a common chamber enclosing both said reaction well and said nozzles therein; wherein,
each said nozzle terminates proximate a substantially planar bottom surface of said head assembly, and said base assembly includes a substantially planar top surface in opposed relation to said head bottom surface.
2. The polymer synthesis apparatus as defined in claim 1 wherein,
said sliding seal is provided by a balloon seal having one end affixed to one of said head bottom surface and said base top surface, and an opposite end in sliding contact with the other of said base top surface and said head bottom surface.
3. A method of synthesis for building a polymer chain by sequentially adding polymer units to at least one solid support for growing and immobilizing a polymer chain thereon in a liquid reagent, said method comprising the steps of:
A) providing the apparatus of claim 1 ;
B) depositing a liquid reagent in a reaction well in contact with at least one solid support and at least one polymer unit of said polymer chain affixed to said solid support, said well having at least one orifice extending into said well, and being of a size and dimension to form a capillary liquid seal to retain said reagent solution in said well to enable polymer chain growth on said solid support; and
C) applying a first gas pressure to said reaction well such that a pressure differential between said first gas pressure and a second gas pressure exerted on an exit of said orifice exceeds a predetermined amount necessary to overcome said capillary liquid seal and expel said reagent solution from said well through said orifice.
4. The method of synthesis for building a polymer chain as described in claim 3 further comprising the step of:
controlling said pressure differential through a pressure regulating device for one of raising said pressure differential above said predetermined amount and lowering said pressure differential below said predetermined amount.
5. The method of synthesis for building a polymer chain as described in claim 3 further comprising the step of:
repeating steps A and B to form at least one continuous chain of polymer units.
6. The method of synthesis for building a polymer chain as described in claim 3 wherein, said predetermined amount is between about 1/100th psi to about 1/10th psi.
7. The method of synthesis for building a polymer chain as described in claim 3 wherein, said polymer chain is provided by a sequence of DNA monomer units.
8. The method of synthesis for building a polymer chain as described in claim 3 , further including the step of:
before said depositing step, placing a filter membrane over said orifice positioned at a bottom portion of said reaction well.
9. The method of synthesis for building a polymer chain as described in claim 3 wherein,
said depositing step is accomplished by droplet delivery of said liquid reagent solution in a vertical direction into said well.
10. The method of synthesis for building a polymer chain as described in claim 9 wherein,
said depositing step further includes the step of ejecting droplets from a nozzle at an ejection velocity sufficient to cause mixing in said well for synthesis of a polymer chain, and further being insufficient in velocity to cause splashing of said liquid reagent outside of said well upon delivery.
11. The method of synthesis for building a polymer chain as described in claim 3 wherein,
the reaction well is contained in a base assembly including a plurality of wells closely aligned in an array and enclosed in a common chamber.
12. The method of claim 3 , wherein said pressure differential is created by forming a vacuum.