1. Field of the Invention
The present invention relates generally to apparatuses for chemical synthesis. More particular, it relates to fluidic devices and related technologies, and to chemical processes using such devices. More specifically, the invention relates to synthesis of radioactive compounds for imaging, such as by positron emission tomography (PET), in an efficient manner. In particular, embodiments of the present invention relate to modular components of a synthesis system or kit that allows an operator to easily change and move components, which makes the system more versatile in synthesizing different compounds and elements. In other words, the system is substantially “universal” in that it can be easily used to synthesize many different chemicals and elements.
2. Description of Related Art
As new radio-labeled compounds are introduced to the market with more complex synthesis procedures, design of a synthesis unit capable of addressing all the processes can result in utilization of complex hardware, plumbing, and excessive use of components that can result in higher risk of nodal failure. Additionally, serviceability of the units can be greatly affected by such a complex setup, thereby affecting the appeal and competitiveness of the instrument with respect to other devices in the market.
In one embodiment, the present invention is a kit for synthesizing a compound or element. The kit includes a modular reagent source comprising a reagent, and a modular trap and release apparatus. The modular trap and release apparatus includes an apparatus configured to separate components of the reagent and a modular reaction block/unit in fluid communication with the modular reagent source and the modular trap and release apparatus. The modular reaction block/unit includes a reaction vessel configured to facilitate a chemical reaction. The kit may also include a modular intermediate collection apparatus in fluid communication with the modular reaction block/unit, where the modular intermediate collection apparatus comprises an intermediate collection vial.
One advantage of this invention is that it enables rapid modification and design of production line for synthesis of various radio-labeled compounds. In some embodiments, the concept of this invention is analogous to circuit design and assembly in electronics applications.
One goal of the modular multi-line radio-synthesis unit is to modularize and simplify design and selection of components needed for reliable, repeatable, and straightforward production of radio-labeled compounds. As new radio-labeled compounds are introduced to the market with more complex synthesis procedures, design of a synthesis unit capable of addressing all the processes can result in utilization of complex hardware, plumbing, and excessive use of component that can result in higher risk of nodal failure. Additionally, serviceability of the units can be greatly affected by such a complex setup, thereby affecting the appeal and competitiveness of the instrument with respect to other devices in the market.
The invention simplifies the overall structure of the synthesis system and peripheral instrumentation, and reduces the complexity of the components. It also provides broader range of synthesis architecture. Easy, fool-proof, non-expert installation and replacement of the components are directly affected by this invention. From the operational conditions of the device, it will provide higher degrees of reliability and good manufacturing processes along with ease of use and service.
The modular nature of the present invention helps placing the components of a synthesis unit together rather easily. The concept may be likened to an electronic circuit board in some respects. This modular concept allows use of single-use, GMP (Good Manufacturing Practice) oriented parts for clinical dose productions if need be. The use of two- and three-way valves allows easier control of flow through the system. Also, using solid blocks with internal plumbing and electrical connections eliminates fittings, and too many wires and tubes going back and forth between the components. Preferably, the modular components herein are not connected via traditional tubes, which may wear out easily and/or become contaminated. In addition, any or all of the modular components below, may be disposable.
It is to be understood that the figures and descriptions of the present invention have been simplified to illustrate elements that are relevant for a clear understanding of the present invention, while eliminating, for purposes of clarity, many other elements which are conventional in this art. Those of ordinary skill in the art will recognize that other elements are desirable for implementing the present invention. However, because such elements are well known in the art, and because they do not facilitate a better understanding of the present invention, a discussion of such elements is not provided herein.
The present invention will now be described in detail on the basis of exemplary embodiments.
In a preferred embodiment, the system is configured to store, transport, facilitate the reaction of, etc., of volumes up to about 100 mL. However, it may facilitate smaller amounts of about 1 mL to 10 mL.
In another embodiment, each component of the system is microfluidic. The terms “microfluidic device”, “microfluidic chip”, “synthesis chip”, and “chip” refer to a unit or device that permits the manipulation and transfer of small amounts of liquid of as much as 10 milliliters (e.g., microliters (1 μL to less than 1 mL), nanoliters (1 nl to less than 1μ), etc.) into a substrate comprising micro-channels and micro-compartments. The microfluidic device may be configured to allow the manipulation of liquids, including reagents and solvents, to be transferred or conveyed within the micro-channels and reaction chamber using mechanical or non-mechanical pumps.
As shown in
As shown in
The modular intermediate collection apparatus 18 may be in fluid communication with a purification system 20, which may be in fluid communication with the modular trap and release apparatus 14. The modular intermediate collection apparatus 18 may also be in fluid communication with a product collection container or apparatus 22. To form a production line using the sub-modules, a series of plumbing and electrical connections may be used to form the network of fluids and signals required for sequential performance of the box. In addition, the system may be fully automated. It is noted that the system 10 may comprise other elements such as various waste collection vials, and vials for collection of raw and/or purified product.
The modular components may be in fluid communication via at least one docking station (not shown). The docking station may provide the fluid lines or channels that connect the modular components. The docking station may also comprise any electrical components necessary to operate the various valves, heating elements, etc., that may be a part of the various modular components. These electrical components may also provide for automated operation of the kit or system when interfaced with a computer.
To form a “production line” using the modular components, a series of plumbing and electrical connections may be used to form the network of fluids and signals required for sequential performance of the system. In one embodiment, each component of the system may be attachable to a fluidic “breadboard”, “circuit board”, or “docking station.” In this embodiment, the desired components are in fluid communication with a bread board that comprises a series of channels for transporting reagents (fluids, gases, etc.). For example, the modular reaction block 16 is attached to the bread board, as are the modular trap and release apparatus 14 and the modular reagent source 12. These components are in fluid communication with each other via at least one channel in the bread board. The components may be in fluid communication with the bread board via a number of means. Preferably, an outlet of the component is connected to the bread board via a washer. In addition, various valves may be used to control the flow to and throughout the breadboard. Such valves may include both 2-way and 3-way valves. Preferably, gas pushes the liquids to and from the modular components. As such, at least one component, possibly the docking station, is coupled to a gas source. It is noted that the entire system may also be connected to external systems such as purifications systems, for example, HPLC columns.
As shown in
The reaction vessel 28 may be almost any size and/or shape. For example, the reaction vessel 28 may be “coin-shaped” as shown in U.S. Ser. No. 11/540,344. In one embodiment, the reaction vessel 28 is configured to facilitate the reaction of a microfluidic amount of reagent. In another embodiment, it may have a hold volume in the milliliter amounts; for example, 1 mL to about 20 mL. Preferably, the reaction chamber 28 has a hold volume of about 1 mL to about 10 mL. In other embodiments, the reaction chamber 28 may have a smaller hold volume; for example, of about 1 microliter to about 100 microliters It may also be elongated; for example, a vial as shown in
The inlets/outlets 36 may be in fluid communication with a separation apparatus 38, configured to separate components of the reagent, via channels 42, which are preferably within the block. In one embodiment, the channels 42 are sized to transport milliliters of reagent. In particular, the channels 42 may be up to about 200 micrometers wide and larger (e.g., 1000 micrometers wide).
The modular trap and release apparatus 14 comprises at least one separation apparatus 38 configured to trap and release chemicals, atoms, etc. In this way, the separation apparatus 38 is configured to separate components of a reagent. Such an apparatus 38 may be a Solid Phase Extraction (SPE) cartridge with a two-stage flow of liquid through the SPE for trapping and releasing. The building block considered for this process may consist of multi-line, single use SPE sub-modules. The embodiment shown in
As shown in
The reagent vials 46 also comprise at least one outlet 54, which may be in fluid communication with the modular trapping and release block 14, and/or the modular reaction vessel 16 or other components of the kit or system 10. The modular reagent block 12 may also comprise at least one inlet 56 (
The modular reagent source or vial magazine 12 may be attached to the stationary pluming dock station (not shown) leading to the reaction chamber module 16 and/or the trap/release module 14.
The modular intermediate collection apparatus 18 comprises at least one and preferably two collection vials 58, 60. Such vials 58, 60 may be virtually any shape as long as they can store an adequate amount of reagent and/or product. In one embodiment, the vials 58, 60 are configured to store milliliters of reagent. As such, they have a hold volume of about 1 mL to about 1000 mL; preferably about 10 mL. In other embodiments, they may hold 1 microliter to about 100 microliters; preferably 1 microliter to 10 microliters. The modular intermediate collection apparatus 18 may comprise a block 62. The block 62 may be comprised of a substantially rigid or flexible material. Such materials may comprise a polymer, metal, wood, etc. Preferably, the block 62 is comprised of the same material as the block of the reaction block and the trap and release block.
Each vial 58, 60 is in fluid communication with a set of inlets 66 and at least one outlet 70 via a set of channels 68 and a set of valves 64. Preferably, the channels 68 are within the block 62. In one embodiment, the inlets 66, outlets 70, and channels 68 are configured to facilitate the passage of milliliters of reagent. In particular, the channels 68 may be about 200 micrometers wide or larger and about 40 to 50 micrometers tall and larger. The valves 64 may be 2-way or 3-way valves. They may also be double valves. In one embodiment, at least one of the inlets 66 receives a gas such as N2. Another inlet 66 may receive product from an outlet 26 of the modular reaction block 16 and/or the trap and release block 14. At least one outlet 70 may dispense product to a purification system 20 and/or to a final product holding storage/vial 22 (e.g., a vial, a vial module, a general storage chamber, etc.).
While this invention has been described in conjunction with the specific embodiments outlined above, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, the preferred embodiments of the invention as set forth above are intended to be illustrative, not limiting. A variety of modifications to the embodiments described will be apparent to those skilled in the art from the disclosure provided herein. Thus, the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. Various changes may be made without departing from the spirit and scope of the inventions as defined in the following claims.
The present application claims priority from Provisional U.S. Patent Application No. 61/385,647 filed on Sep. 23, 2010, the disclosure of which is incorporated herein by reference in its entirety.
Number | Date | Country | |
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61385647 | Sep 2010 | US |