Synthesis apparatus and method
Apparatus for biochemical synthesis having a reaction vessel, a temperature control device for the reaction vessel, a plurality of reservoirs for reaction components, and supply/withdrawal systems, e.g. reciprocating syringe pumps and switchable valves. Agitation of a reaction mixture is effected by withdrawing a part of the mixture from the reaction vessel and returning it thereto.
1. A synthesis apparatus comprising:
a reaction vessel having a first lower port and a second upper port;
a temperature control device for controlling the temperature of the reaction vessel;
a plurality of reservoirs for holding reaction components;
a plurality of conduits, each of the plurality of conduits connecting the second upper port of the reaction vessel with a respective one of the plurality of reservoirs;
a pressure sensor configured to measure pressure of content in a conduit external to said reaction vessel that connects an agitation device-to the reaction vessel;
a supply pump configured to selectively supply controlled amounts of reaction components held in the plurality of reservoirs to the reaction vessel at desired times; and
a controller configured to control the supply pump and the agitation device;
wherein the agitation device is configured to selectively withdraw an amount of content from the reaction vessel through the first lower port thereof and selectively return the withdrawn content to the reaction vessel through the first lower port thereof; and
wherein the pressure sensor is configured to send a signal to the controller, the signal being indicative of a pressure in the conduit connecting the agitation device to the reaction vessel that can be used to infer the viscosity of the mixed reaction components, and
wherein the controller is configured to control the rate of withdrawal from or return of reactants to the reaction vessel, using the agitation device, in response to a change in the signal received from the pressure sensor, thereby ensuring that a predefined pressure limit is not exceeded and that the mixed reaction components are not damaged by high shear forces.
2. The synthesis apparatus according to claim 1 wherein the reaction vessel is arranged so that it tapers towards its lowest point and has an inlet/outlet port at the lowest point.
3. The synthesis apparatus according to claim 1 wherein the aspect ratio of the reaction vessel is in the range of from 5:1 to 8:1.
4. The synthesis apparatus according to claim 1 wherein the temperature control device is arranged to control the temperature of the reaction vessel to follow a desired temperature profile upon the addition of reaction components and/or withdrawal of material.
5. The synthesis apparatus according to claim 1 further comprising a reservoir temperature control device arranged to control the temperature of a reaction component held in the plurality of reservoirs.
6. The synthesis apparatus according to claim 1 wherein the temperature control device comprises a thermocirculator, a Peltier heating/cooling device and/or a resistive heater.
7. The synthesis apparatus according to claim 1 wherein the supply pump and the agitation device comprise reciprocating syringe pumps.
8. The synthesis apparatus according to claim 1 wherein the supply pump comprises a multi-way valve arranged to selectively connect the supply pump to the first port of the reaction vessel or a reservoir.
9. The synthesis apparatus according to claim 1 wherein at least one reservoir comprises a glass or polypropylene removable syringe.
10. The synthesis apparatus according to claim 1 wherein the agitation device comprises a multi-way valve arranged to selectively connect the agitation device to the second port of the reaction vessel or a reservoir.