Chemical synthesis using solvent microdroplets
AssigneeUniversity of Washington
InventorAlan P. Blanchard
Life of this patent
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Abstract
The present invention relates to microdroplets of a solution comprising a solvent having a boiling point of 150° C. or above, a surface tension of 30 dynes/cm or above, and a viscosity of 0.015 g/(cm)(sec). Such microdroplets are useful for the synthesis of chemical species, particularly biopolymers such as oligonucleotides and peptides, as well as arrays of chemical species. Preferably, the solvent has the formula (I): wherein A=O or S; X=O, S or N (C1-C4 alkyl) Y=O, S, N(C1-C4 alkyl) or CH2; and R=C1-C20 straight or branched chain alkyl.
Claims95
An automated system capable of processing one or more substrates, comprising:
- an inkjet print head for spraying a microdroplet comprising a chemical species on a substrate;
- a scanning transport for scanning the substrate adjacent to the print head to selectively deposit the microdroplet at specified sites;
- a flow cell for treating the substrate on which the microdroplet is deposited by exposing the substrate to one or more selected fluids;
- a treating transport for moving the substrate between the print head and the flow cell for treatment in the flow cell, wherein said treating transport and said scanning transport are different elements;
- and
- an alignment unit for aligning the substrate correctly relative to the print head each time when the substrate is positioned adjacent to the print head for deposition.
An automated system for synthesizing oligonucleotides on a substrate, said automated system capable of processing one or more substrates, comprising:
- an inkjet print head for spraying a solution comprising a nucleoside or activated nucleoside on a substrate;
- a scanning transport for scanning the substrate adjacent to the print head to selectively deposit the nucleoside at specified sites;
- a flow cell for treating the substrate on which the monomer is deposited by exposing the substrate to one or more selected fluids;
- a treating transport for moving the substrate between the print head and the flow cell for treatment in the flow cell, wherein said treating transport and said scanning transport are different elements;
- and
- an alignment unit for aligning the substrate correctly relative to the print head each time when the substrate is positioned adjacent to the print head for deposition.
A method of controlling a system for synthesizing a biopolymer on a substrate, said system capable of processing one or more substrates, using a computer having a memory for storing a control program and data, wherein the system comprises an inkjet print head for spraying a microdroplet on the substrate, a scanning transport for scanning the substrate adjacent to the print head to selectively deposit the microdroplet, an alignment unit for detecting misalignment of the substrate with respect to the print head at each deposition step, a flow cell for treating the substrate, and a treating transport for moving the substrate between the printer head and the flow cell, wherein said treating transport and said scanning transport are different elements, the method comprising the steps of:
- (a) aligning the substrate relative to the print head by processing data from the alignment unit and by sending a signal to the scanning transport to move the substrate so as to correct misalignment of the substrate;
- (b) selectively depositing a microdroplet on the substrate by sending a signal to the print head to spray the microdroplet and by sending a signal to the scanning transport to move the substrate adjacent to the print head so that the microdroplet can be deposited at specified loci on the substrate;
- and
- (c) controlling treatment of the substrate by sending a signal to the treating transport to move the substrate to the flow cell and by sending a signal to the flow cell to control operation of the flow cell.
A method of controlling a system for synthesizing oligonucleotides on a substrate, said system capable of processing one or more substrates, using a computer having a memory for storing a control program and data, wherein the system comprises an inkjet print head for spraying a solution comprising a nucleoside or activated nucleoside, on the substrate, a scanning transport for scanning the substrate adjacent to the print head to selectively deposit the solution, an alignment unit for detecting misalignment of the substrate with respect to the print head at each deposition step, a flow cell for treating the substrate, and a treating transport for moving the substrate between the printer head and the flow cell, wherein said treating transport and said scanning transport are different elements, the method comprising the steps of:
- (a) placing the substrate with respect to the print head and establishing marks on the substrate;
- (b) selectively depositing the solution on the substrate by sending a signal to the print head to spray the solution and by sending a signal to the scanning transport to move the substrate adjacent to the print head so that the solution can be deposited at specified loci on the substrate;
- (c) controlling treatment of the substrate by sending a signal to the treating transport to move the substrate to the flow cell and by sending a signal to the flow cell to control operation of the flow cell;
- and
- (d) placing the substrate adjacent to the print head and aligning the substrate with respect to the print head by processing data from the alignment unit and by sending a signal to the scanning transport to move the substrate so as to correct misalignment of the substrate.
An automated system for synthesizing oligonucleotides on a substrate, said automated system capable of processing one or more substrates, comprising:
- an inkjet print head having an array of pumps for depositing a nucleoside or activated nucleoside at specified loci on the substrate;
- a first translational stage having at least two axes of movement;
- a first substrate chuck mounted for movement by the translational stage, the first substrate chuck being adapted to hold the substrate and move adjacent to the print head;
- a flow cell that receives the substrate and that exposes the substrate to one or more selected fluids;
- a second translational stage that has at least two axes of movement, wherein said first translational stage and said second translational stage are different elements;
- a second substrate chuck mounted for movement by the second translational stage, the second substrate chuck being adapted to hold the substrate and move between the print head and the flow cell;
- control logic connected to control movement of the first and second translational stages;
- a marker positioned adjacent to the print head that can be activated to mark particular loci on the substrate for positionally calibrating the substrate with respect to the print head;
- and
- a camera positioned adjacent to the print head to positionally calibrate the substrate with respect to the print head, wherein the camera is connected to provide images to the control logic.
An apparatus programmed for controlling a system for synthesizing a biopolymer on a substrate, said system capable of processing one or more substrates, wherein the system comprises an inkjet print head for spraying a microdroplet on the substrate, a scanning transport for scanning the substrate adjacent to the print head to selectively deposit the microdroplet, an alignment unit for detecting misalignment of the substrate with respect to the print head at each deposition step, a flow cell for treating the substrate, and a treating transport for moving the substrate between the printer head and the flow cell, wherein said treating transport and said scanning transport are different elements, the controller comprising:
- (a) means for controlling alignment of the substrate relative to the print head by processing data from the alignment unit and by sending a signal to the scanning transport to move the substrate so as to correct misalignment of the substrate;
- (b) means for controlling selective deposition of a microdroplet on the substrate by sending a signal to the print head to spray the microdroplet and by sending a signal to the scanning transport to move the substrate adjacent to the print head so that the microdroplet can be deposited at specified loci on the substrate;
- and
- (c) means for controlling treatment of the substrate by sending a signal to the treating transport to move the substrate to the flow cell and by sending a signal to the flow cell to control operation of the flow cell.
The apparatus of claim wherein said solvent is propylene carbonate.
An apparatus programmed for controlling a system for synthesizing a biopolymer on a substrate, said system capable of processing one or more substrates, wherein the system comprises an inkjet print head for spraying a microdroplet on the substrate, a scanning transport for scanning the substrate adjacent to the print head to selectively deposit the microdroplet, an alignment unit for detecting misalignment of the substrate with respect to the print head at each deposition step, a flow cell for treating the substrate, and a treating transport for moving the substrate between the printer head and the flow cell, wherein said treating transport and said scanning transport are different elements, said apparatus comprising one or more computer systems programmed for:
- (a) controlling alignment of the substrate relative to the print head by processing data from the alignment unit and by sending a signal to the scanning transport to move the substrate so as to correct misalignment of the substrate;
- (b) controlling selective deposition of a microdroplet on the substrate by sending a signal to the print head to spray the microdroplet and by sending a signal to the scanning transport to move the substrate adjacent to the print head so that the microdroplet can be deposited at specified loci on the substrate;
- and
- (c) controlling treatment of the substrate by sending a signal to the treating transport to move the substrate to the flow cell and by sending a signal to the flow cell to control operation of the flow cell.
Dependencies are inferred from the claim text.