Abstract: A microfluidic chip device for the purification of radiochemical compounds includes a chip having an injection channel and intersecting branch channels with a plurality of valves are located along the injection channel and branch channels and configured to retain a plug of solution containing the radiochemical compound. The chip further includes a serpentine channel segment (for separation) coupled to the output of the injection channel. A high voltage power source advances the plug of solution through the purification region and into the downstream fraction collection channel. The chip includes a downstream fraction collection channel coupled to the serpentine channel segment and having an optical and radiation detection regions. One or more branch fraction channels intersect with the fraction collection channel and include valves located therein so that the radiochemical compound that is detected using a radiation detector is directed into the desired branch fraction channel for subsequent use.

Abstract: 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).

Abstract: A chemical synthesis platform based on a particularly simple chip is described herein, where reactions take place atop a hydrophobic substrate patterned with a circular hydrophilic liquid trap. The overall supporting hardware (heater, rotating carousel of reagent dispensers, etc.) can be packaged into a very compact format (about the size of a coffee cup). We demonstrate the consistent synthesis of [18F]fallypride with high yield, and show that protocols optimized using a high-throughput optimization platform we have developed can be readily translated to this device with no changes or reoptimization.

Abstract: A method of performing high-throughput radio thin layer chromatography (radio-TLC) includes spotting a plurality of locations on one or more TLC plates with samples containing a radiochemical or a radiopharmaceutical, each location defining an individual lane on the one or more TLC plates for the respective samples. The one or more TLC plates are developed with a developing solution and dried. The TLC plates are imaged with an imaging device comprising a camera, wherein the image obtained from the camera comprises a field of view that contains regions of interest (ROIs) from the plurality of lanes. The ROIs in the images obtained from the camera may then be analyzed by the user. The ROIs may be used, for example, reaction optimization or for quality control check of the production of radiotracers.

Abstract: A microfluidic synthesis platform includes a microfluidic chip holder that has a computer controlled heating element and cooling element therein. A microfluidic chip is mountable in the microfluidic chip holder. The microfluidic chip is formed by a hydrophobic substrate having patterned thereon a hydrophilic reaction site and a plurality of hydrophilic channels or pathways extending outward from the hydrophilic reaction site and terminating at respective loading sites on the substrate, wherein the hydrophilic channels or pathways are tapered with an increasing width in an inward direction toward the hydrophilic reaction site.

Abstract: A volumetric microfluidic injector for capillary electrophoresis (CE) for highly repeatable sample injection has been designed and built to eliminate known injection bias in hydrodynamic injection. A defined volume from 1-10 nL or 0.1-100 nL of sample is confined in a defined region of a micro-valve PDMS microfluidic injector chip and electrophoretic potential is applied to drive sample into a separation device such as an embedded fused silica capillary for separation and detection. Using a 75 ?m ID capillary, the RSD of an absorbance peak area as low as 1.32% (n=11) is obtained. As a comparison, the time-dependent injection was tested using the same chip which resulted in an inferior repeatability.

Abstract: A microfluidic synthesis platform includes a microfluidic chip holder that has a computer controlled heating element and cooling element therein. A microfluidic chip is mountable in the microfluidic chip holder. The microfluidic chip is formed by a hydrophobic substrate having patterned thereon a hydrophilic reaction site and a plurality of hydrophilic channels or pathways extending outward from the hydrophilic reaction site and terminating at respective loading sites on the substrate, wherein the hydrophilic channels or pathways are tapered with an increasing width in an inward direction toward the hydrophilic reaction site.

Abstract: A microfluidic chip device for the purification of radiochemical compounds includes a chip having an injection channel and intersecting branch channels with a plurality of valves are located along the injection channel and branch channels and configured to retain a plug of solution containing the radiochemical compound. The chip further includes a serpentine channel segment (for separation) coupled to the output of the injection channel. A high voltage power source advances the plug of solution through the purification region and into the downstream fraction collection channel. The chip includes a downstream fraction collection channel coupled to the serpentine channel segment and having an optical and radiation detection regions. One or more branch fraction channels intersect with the fraction collection channel and include valves located therein so that the radiochemical compound that is detected using a radiation detector is directed into the desired branch fraction channel for subsequent use.

Abstract: A device for purifying and formulating a radiopharmaceutical compound includes an automated purification subsystem that automates the loading of a sample into a sample loop for downstream purification via HPLC. A column selector valve is provided to select from one of a plurality of columns. Fractions can be collected as well as the desired product. The device includes an automated formulation subsystem that first sends the product to a dilution reservoir prior to being pneumatically pushed onto a solid phase extraction (SPE) cartridge. Automated rinse, elution, and reconstitution are also performed with the automated formulation subsystem. The device may be directly coupled to the output of an automated radiosynthesizer.

Abstract: A volumetric microfluidic injector for capillary electrophoresis (CE) for highly repeatable sample injection has been designed and built to eliminate known injection bias in hydrodynamic injection. A defined volume from 1-10 nL or 0.1-100 nL of sample is confined in a defined region of a micro-valve PDMS microfluidic injector chip and electrophoretic potential is applied to drive sample into a separation device such as an embedded fused silica capillary for separation and detection. Using a 75 ?m ID capillary, the RSD of an absorbance peak area as low as 1.32% (n=11) is obtained. As a comparison, the time-dependent injection was tested using the same chip which resulted in an inferior repeatability.

Abstract: A self-shielded, bench-top radiochemistry system, including a radioactive isotope dispensing module configured to draw an isotope out of a vial and dispense one or more metered doses of the isotope to a concentration module that concentrates the metered dose into a droplet amount of isotope and a synthesizer module that delivers the droplet amount of isotope along with one or more reagents to an electrowetting on dielectrics (EWOD) chip to produce a radiolabeled molecule.

Abstract: A method of formulating or concentrating a radiolabeled molecule or compound includes providing a microfluidic device having a sample layer containing a microfluidic channel formed therein, a porous membrane having a pore size of less than 0.5 ?m disposed on the sample layer and covering the microfluidic channel, and a gas flow layer having a gas-carrying channel formed therein, wherein the porous membrane is interposed between the sample layer and the gas flow layer. A fluid containing the radiolabeled molecule or compound is delivered into the microfluidic channel. Heat is applied to evaporate the fluid. A gas is passed through gas-carrying channel to remove evaporated fluid from the microfluidic device.

Abstract: An automated radiosynthesizer device includes a plurality of reactor assemblies, each reactor assembly being operatively connected to a horizontal actuator for moving the reactor assembly in the horizontal direction and a vertical actuator for moving the reactor assembly in the vertical direction. A plurality of disposable cassettes are disposed above each of the plurality of reactor assemblies, each cassette comprising a lower surface comprising a plurality of sealed and un-sealed gaskets, wherein the un-sealed gaskets are connected to internal fluid paths within the cassette. The device includes a three-axis reagent and gas handling robot disposed above the plurality of cassettes and terminates in a vial gripper and a gas manifold having an inert gas port and a vacuum port. The device includes a control system configured to control the horizontal actuator and vertical actuator of each reactor assembly and the three-axis reagent and gas handling robot.

Abstract: A device for purifying and formulating a radiopharmaceutical compound includes an automated purification subsystem that automates the loading of a sample into a sample loop for downstream purification via HPLC. A column selector valve is provided to select from one of a plurality of columns. Fractions can be collected as well as the desired product. The device includes an automated formulation subsystem that first sends the product to a dilution reservoir prior to being pneumatically pushed onto a solid phase extraction (SPE) cartridge. Automated rinse, elution, and reconstitution are also performed with the automated formulation subsystem. The device may be directly coupled to the output of an automated radiosynthesizer.

Abstract: The present disclosure sets forth incorporating microfluidic chips interfaces for use with digital microfluidic processes. Methods and devices according to the present disclosure utilize compact, integrated platforms that interface with a chip upstream and downstream of the reaction, as well as between intermediate reaction steps if needed. In some embodiments these interfaces are automated, including automation of a multiple reagent process. Various reagent delivery systems and methods are also disclosed.

Abstract: A self-shielded, bench-top radiochemistry system, including a radioactive isotope dispensing module configured to draw an isotope out of a vial and dispense one or more metered doses of the isotope to a concentration module that concentrates the metered dose into a droplet amount of isotope and a synthesizer module that delivers the droplet amount of isotope along with one or more reagents to an electrowetting on dielectrics (EWOD) chip to produce a radiolabeled molecule.

Abstract: Disclosed herein are methods of performing microchemical reactions and electro-wetting-on-dielectric devices (EWOD devices) for use in performing those reactions. These devices and method are particularly suited for preparing radiochemical compounds, particularly compounds containing 18F.

Abstract: A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures.

Abstract: An automated radiosynthesizer device includes a plurality of reactor assemblies, each reactor assembly being operatively connected to a horizontal actuator for moving the reactor assembly in the horizontal direction and a vertical actuator for moving the reactor assembly in the vertical direction. A plurality of disposable cassettes are disposed above each of the plurality of reactor assemblies, each cassette comprising a lower surface comprising a plurality of sealed and un-sealed gaskets, wherein the un-sealed gaskets are connected to internal fluid paths within the cassette. The device includes a three-axis reagent and gas handling robot disposed above the plurality of cassettes and terminates in a vial gripper and a gas manifold having an inert gas port and a vacuum port. The device includes a control system configured to control the horizontal actuator and vertical actuator of each reactor assembly and the three-axis reagent and gas handling robot.

Abstract: A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures.