High throughput radiochemistry system
A radiosynthesis system is disclosed that leverages droplet microfluidic radiosynthesis and its inherent advantages including reduction of reagent consumption and the ability to achieve high molar activity even when using low starting radioactivity. The radiosynthesis system enables the parallel synthesis of radiolabeled compounds using droplet-sized reaction volumes. In some embodiments, a single heater is used to create multiple reaction or synthesis sites. In other embodiments, separate heaters are used to create independently-controlled heating conditions at the multiple reaction or synthesis sites. In one embodiment, a four-heater setup was developed that utilizes a multi-reaction microfluidic chip and was assessed for the suitability with high-throughput radiosynthesis optimization. Replicates of several radiochemical operations including the full synthesis of various PET tracers revealed the platform to have high repeatability (e.g., consistent fluorination efficiency). The system may also be used for synthesis optimization.
1 . A high throughput radiochemistry system comprising:
a frame including a base plate;
a heater platform disposed on the base plate and containing a plurality of heaters therein and defining a flat upper surface configured to hold a plurality of microfluidic chips or substrates thereon, wherein the plurality of microfluidic chips or substrates have a plurality of reaction sites formed thereon, the heater platform containing a plurality of controllable heaters each coupled to heater control circuitry;
one or more cooling devices in thermal contact with the heater platform;
a robotic system for reagent dispensing and product collecting/sampling, the robotic system comprising a robotic moveable gantry configured to move in the x, y, and z direction and having a head secured to the moveable gantry, the head having a plurality of dispensers and a pipette cone disposed therein, wherein the pipette cone is secured to an actuator via a bracket and configured to move the pipette cone in the z direction independent of the robotic moveable gantry;
a controller programed to manipulate the moveable gantry, the plurality of dispensers, and actuator; and
one or more microwell storage areas and at least one or more pipette tip racks disposed in respective nests disposed on the base plate.
2 . The system of claim 1 , wherein the heater control circuitry comprises a temperature sensor associated with each of the plurality of heaters and respective relays.
3 . The system of claim 1 , wherein the actuator comprises a pneumatic actuator.
4 . The system of claim 1 , wherein the one or more cooling devices comprises one or more of: a fan, a heat sink, a heat pipe, a liquid cooler, evaporative cooler, and a thermoelectric cooler.
5 . The system of 1 , further comprising a priming sensor, the priming sensor comprising a notch or partial opening and a light beam emitter and receiver disposed across the notch or partial opening.
6 . The system of claim 1 , wherein the system comprises a base plate containing a nest for holding one or more TLC plate holders.
7 . The system of claim 6 , wherein each of the TLC plate holders comprises a plurality of TLC plates stacked in a staggered configuration.
8 . The system of claim 1 , further comprising a pipette removal fork disposed on the base plate.
9 . The system of claim 1 , wherein the heater platform comprises a ceramic holder having the plurality of heaters potted in the ceramic holder.
10 . The system of claim 1 , wherein the heater platform comprises at least four heaters.
11 . The system of claim 1 , further comprising a chromatography system for analysis or purification of radiochemicals obtained from the reaction sites.
12 . The system of claim 1 , the frame further comprising a top, sides, and back braces.
13 . The system of claim 1 , wherein the plurality of dispensers comprise non-contact dispensers.
14 . The system of claim 1 , wherein the heater platform is supported on the base plate by a plurality of stands and wherein the one or more cooling devices comprise respective fans disposed beneath the plurality of heaters.
15 . The system of claim 14 , wherein the respective fans are mounted to a base secured to the heater platform, wherein the base further comprises a plurality of exhaust vents.