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Nucleic Acid Synthesizers

a technology of nucleic acid and synthesizer, applied in the field of nucleic acid synthesizer, can solve the problems of reducing or losing the synthesis efficiency, normal operation, and emitted undesirable gaseous or liquid materials, and achieve the effect of reducing or preventing the flow of fumes and emissions

Inactive Publication Date: 2009-02-12
THIRD WAVE TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]The present invention relates to nucleic acid synthesizers and methods of using and modifying nucleic acid synthesizers. For example, the present invention provides highly efficient, reliable, and safe synthesizers that find use, for example, in high throughput and automated nucleic acid synthesis, as well as methods of modifying pre-existing synthesizers to improve efficiency, reliability, and safety. The present invention also relates to synthesizer arrays for efficient, safe, and automated processes for the production of large quantities of oligonucleotides.
[0016]In some embodiments, the systems of the present invention comprise an integrated ventilation system, e.g., a fume hood, wherein the fume hood is configured to draw gaseous emissions away from an instrument operator. In some embodiments, the integrated fume hood comprises side panels and a front panel, wherein said side and front panels create a ventilated workspace having negative air pressure when compared with the ambient environment. In preferred embodiments, the side and front panels create the ventilated workspace when the synthesizer is opened, e.g., for operator access to the reaction enclosure. In some embodiments, the panels fold or slide into recesses in the synthesizer body upon closing of the instrument, such that the instrument can be closed without removal of the panels.
[0021]In some embodiments, the synthesizer further comprises providing energy, such as heat, to the synthesis columns. Heating of the synthesis column finds use, for example, in decreasing the coupling time during a nucleic acid synthesis. It can also broaden the range of the chemical protocols that can be used in high throughput synthesis, e.g. by improving the efficiency of less efficient chemistries, such as the phosphate triester method of oligonucleotide synthesis. In other embodiments, the synthesizer further comprises a mixing component, such as an agitator, configured to agitate the synthesis columns (e.g., to mix reaction components, and to facilitate mass exchange between the reaction medium and the solid support).
[0026]In some embodiments, the present invention provides a nucleic acid synthesizer comprising a plurality of synthesis columns and an energy input component that imparts energy to said plurality of synthesis columns to increase nucleic acid synthesis reaction rate in said plurality of synthesis columns. In some embodiments, said energy input component comprises a heating component. In preferred embodiments, said heating component provides substantially uniform heat. In some embodiments, said energy input component provides heated reagent solutions to said plurality of synthesis columns. In other embodiments, said energy input component comprises a heating coil. In yet other embodiments, said energy input component comprises a heat blanket. In yet other embodiments, said heating component comprises a resistance heater, a Peltier device, a magnetic induction device or a microwave device. In still other embodiments, said energy input component comprises a heated room. In further embodiments, said energy input component provides energy in the electromagnetic spectrum. In yet other embodiments, said energy input component comprises an oscillating member. In some embodiments, said energy input component provides a periodic energy input, and in other embodiments, said energy input component provides a constant energy input.

Problems solved by technology

A problem with currently available synthesizers is the emission of undesirable gaseous or liquid materials that pose health, environmental, and explosive hazards.
Such emissions result from both the normal operation of the instrument and from instrument failures.
Emissions that result from instrument failures cause a reduction or loss of synthesis efficiency and can provoke further failures and / or complete synthesizer failure.

Method used

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Examples

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example 1

The Northwest Engineering 48-Column Oligonucleotide Synthesizer

[0305]The Northwest Engineering 48-Column Oligonucleotide Synthesizer (NEI-48, Northwest Engineering, Inc., Alameda, Calif.) is an “open system” synthesizer in that the dispensing tubes for the delivery of reagents are not affixed to each synthesis vial or column for the entire term of the synthesis process. Instead, movement of a round cartridge containing the columns allows each dispensing tube to serve multiple columns. In addition, when a synthesis column is positioned to receive reagent, the dispenser is not even temporarily affixed to the vial with a sealed coupling. The reagent dispensed to the vial has open contact with the surrounding environment of the chamber. The chamber containing the synthesis vials is isolated from the ambient environment by a top plate. The general design and operation of the NEI instrument is described in WO 99 / 656602.

[0306]The NEI-48 synthesizer includes external mounting points for var...

example 2

The Applied Biosystems 3900 Oligonucleotide Synthesizer

[0318]The Applied Biosystems 3900 Oligonucleotide Synthesizer (Applied Biosystems, Foster City, Calif.) is similar in design and function to the NEI-48, described above. The 3900 is an “open system” synthesizer utilizing a round cartridge containing the columns. The receiving holes of the cartridge are essentially cylindrical, and, as with the NEI-48, proper function of the instrument relies on an airtight seal between the columns and cartridge.

[0319]The 3900 synthesizer includes recessed areas for the external mounting of reagent bottles. When mounted on the instrument, the reagent bottles do not protrude beyond the outside edges of the instrument; they are completely recessed, (as, e.g., the reagent reservoirs 72 are recessed in base 2, diagrammed in FIG. 13A). As with the NEI-48, the reagent feeding is done under pressure from an argon gas source.

[0320]The performance of the 3900 synthesizer is improved using the modification...

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Abstract

The present invention relates to nucleic acid synthesizers and methods of using and modifying nucleic acid synthesizers. For example, the present invention provides highly efficient, reliable, and safe synthesizers that find use, for example, in high throughput and automated nucleic acid synthesis, as well as methods of modifying pre-existing synthesizers to improve efficiency, reliability, and safety.

Description

[0001]This application is a Continuation of application Ser. No. 10 / 054,023, filed on Nov. 13, 2001, which issued on Oct. 14, 2008 as U.S. Pat. No. 7,435,390 and which is incorporated herein by reference, which is a Continuation-in-Part of application Ser. No. 10 / 002,251, filed Oct. 26, 2001, now abandoned, which is a Continuation-in-Part of application Ser. No. 09 / 782,702, filed Feb. 13, 2001, now abandoned, which is a Continuation-in-Part of application Ser. No. 09 / 771,332, filed Jan. 26, 2001, which issued on Aug. 23, 2005 as U.S. Pat. No. 6,932,943.FIELD OF THE INVENTION[0002]The present invention relates to nucleic acid synthesizers and methods of using and modifying nucleic acid synthesizers. For example, the present invention provides highly efficient, reliable, and safe synthesizers that find use, for example, in high throughput and automated nucleic acid synthesis, as well as methods of modifying pre-existing synthesizers to improve efficiency, reliability, and safety. The ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): B01J19/18B01J19/00G06Q10/00G06Q30/00
CPCG06Q30/06G06Q10/087B01J19/0046
Inventor CRACAUER, RAYMOND F.ZIARNO, WITOLD A.
Owner THIRD WAVE TECH
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