Process and apparatus for sequential synthesis of biological polymers
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Publication Number
US-12239950-B2
Publication Date
2025-03-04
Expiration Date
Abstract
A method and apparatus for nucleic acid synthesis. The method employs a device including at least one deprotection unit to carry out a step of deprotection, at least one coupling unit to carry out a step of coupling, at least one oxidation/thiolation unit to carry out a step of oxidation or thiolation, at least one capping unit to carry out a step of capping, and at least one washing unit to carry out a step of washing. A plurality of reaction vessels for nucleic acid synthesis are moved to the units in accord with a synthesis scheme for a desired nucleic acid sequence and at least two reaction vessels are simultaneously acted upon at several of the units in series.
Core Innovation
A device is used for multi-stage synthesis in which a plurality of reaction vessels are moved to units according to a synthesis scheme for a desired nucleic acid sequence. The device includes at least one deprotection unit, at least one coupling unit, at least one oxidation/thiolation unit, and at least one washing unit. At least two reaction vessels are simultaneously acted upon at several of the units in series, and material introduced from one unit into a first reaction vessel is subsequently received in a second reaction vessel.
The synthesis scheme is carried out with parallel operation of stations and with multiple reaction vessels simultaneously acted upon at several units in series. The motion and processing are coordinated with timing relationships using a set period of time (T) and a longest time (R), and reaction vessels with reaction time less than R are kept at their units for a multiple of T. A start-up mode is included in which vessels are moved after a period of reaction time that is a fraction of T until at least one vessel is associated with each station.
For multi-stage synthesis as an apparatus, fluid reservoirs, valve elements, and fluid delivery devices provide feed streams to the plurality of reaction vessels. Monitoring devices monitor chemical composition of effluent from a plurality of vessels, and a conveyor with a programmed pattern transports the vessels sequentially from fluid engagement with one reservoir to a subsequent reservoir according to the programmed pattern. At least two reaction vessels receive a fluid from at least one fluid reservoir simultaneously, and the fluid is introduced into a first vessel and then into a second vessel of the simultaneously receiving vessels.
Claims Coverage
The provided claim set includes two independent claims: a method claim for nucleic acid synthesis and an apparatus claim for multi-stage synthesis of organic molecules. Across these independent claims, the inventive features focus on multi-stage unit operations with simultaneously acted-upon vessels in a serial unit sequence, and an apparatus architecture that couples reservoir-to-vessel fluid engagement with programmed conveyor transport and effluent monitoring.
Simultaneously acted-upon reaction vessels in multi-stage nucleic acid synthesis
A method of nucleic acid synthesis using a device comprising at least one deprotection unit, at least one coupling unit, at least one oxidation/thiolation unit, and at least one washing unit, wherein a plurality of reaction vessels are moved to the units in accord with a synthesis scheme for a desired nucleic acid sequence, and wherein at least two reaction vessels are simultaneously acted upon at several of the units in series such that material introduced from one of the several units into a first of the at least two reaction vessels is subsequently received in a second of the at least two reaction vessels from the first.
Programmed conveyor multi-stage synthesis apparatus with reservoir-to-first-to-second vessel fluid introduction
An apparatus for the multi-stage synthesis of organic molecules comprising a plurality of reaction vessels, a plurality of fluid reservoirs, valve elements associated with said fluid reservoirs, fluid delivery devices providing a feed stream from the fluid reservoirs to said vessels, monitoring devices for chemical composition of effluent from a plurality of said vessels, and a conveyor having a programmed pattern suitable for transporting the vessels from fluid engagement with one fluid reservoir to a subsequent fluid reservoir sequentially according to the programmed pattern, wherein at least two reaction vessels receive a fluid from at least one of the fluid reservoirs simultaneously and wherein the fluid from the at least one of the fluid reservoirs is introduced into a first reaction vessel and from the first reaction vessel into a second reaction vessel of the at least two reaction vessels.
The independent claims jointly cover nucleic acid synthesis performed by moving multiple reaction vessels through deprotection, coupling, oxidation/thiolation, and washing units according to a synthesis scheme while at least two vessels are simultaneously acted upon across units in series, and a multi-stage synthesis apparatus with reservoir/valve/feed-stream architecture, effluent monitoring, and a programmed conveyor pattern enabling simultaneous reservoir-fed introduction into a first vessel and subsequent introduction into a second vessel.
Stated Advantages
Documented Applications
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