Microreactor and method for preparing a radiolabeled complex or a biomolecule conjugate

Abstract

A microreactor for preparing a radiolabeled complex or a biomolecule conjugate comprises a microchannel for fluid flow, where the microchannel comprises a mixing portion comprising one or more passive mixing elements, and a reservoir for incubating a mixed fluid. The reservoir is in fluid communication with the microchannel and is disposed downstream of the mixing portion. A method of preparing a radiolabeled complex includes flowing a radiometal solution comprising a metallic radionuclide through a downstream mixing portion of a microchannel, where the downstream mixing portion includes one or more passive mixing elements, and flowing a ligand solution comprising a bifunctional chelator through the downstream mixing portion. The ligand solution and the radiometal solution are passively mixed while in the downstream mixing portion to initiate a chelation reaction between the metallic radionuclide and the bifunctional chelator. The chelation reaction is completed to form a radiolabeled complex.

What is claimed is: 
     
         1 . A microreactor for preparing a radiolabeled complex or a biomolecule conjugate, the microreactor comprising:
 a microchannel for fluid flow, the microchannel including an upstream mixing portion and a downstream mixing portion each comprising one or more passive mixing elements;   a first inlet upstream of the upstream mixing portion for introduction of a first reagent;   a second inlet upstream of the upstream mixing portion for introduction of a second reagent;   a third inlet between the upstream mixing portion and the downstream mixing portion for introduction of a third reagent; and   at least one reservoir for incubating a mixed fluid, the at least one reservoir being in fluid communication with the microchannel and disposed downstream of the downstream mixing portion.   
     
     
         2 . The microreactor of  claim 1 , wherein the upstream mixing portion is in a first straight portion of the microchannel and the downstream mixing portion is in a second straight portion of the microchannel, the first and second straight portions being connected. 
     
     
         3 . The microreactor of  claim 2 , wherein the microchannel defines a serpentine flow path, the second straight portion being arranged substantially parallel to the first straight portion. 
     
     
         4 . The microreactor of  claim 1 , wherein the one or more passive mixing elements comprise a series of grooves in a wall of the microchannel. 
     
     
         5 . The microreactor of  claim 4 , wherein the series of grooves define a staggered herringbone pattern. 
     
     
         6 . The microreactor of  claim 1 , wherein the upstream and downstream mixing portions each comprise a length of between about 0.1 cm and about 100 cm. 
     
     
         7 . The microreactor of  claim 1 , wherein the microchannel comprises a height of between about 5 microns and about 500 microns. 
     
     
         8 . The microreactor of  claim 1 , wherein the microchannel comprises a width of between about 5 microns and about 500 microns. 
     
     
         9 . The microreactor of  claim 1 , wherein the reservoir has an elongated shape in a direction of the fluid flow. 
     
     
         10 . The microreactor of  claim 9 , wherein a longitudinal cross-section of the elongated shape is a hexagon. 
     
     
         11 . The microreactor of  claim 1 , wherein the reservoir comprises a tapered entrance region connected to a wider central region, the wider central region comprising a width at least about an order of magnitude greater than a width of the microchannel. 
     
     
         12 . The microreactor of  claim 1 , further comprising a plurality of the reservoirs. 
     
     
         13 . The microreactor of  claim 12 , wherein the plurality of the reservoirs are arranged in series. 
     
     
         14 . The microreactor of  claim 12 , wherein the plurality of the reservoirs are arranged in parallel. 
     
     
         15 . The microreactor of  claim 12 , wherein the plurality of the reservoirs comprise a total of volume of between about 5 μL and about 1000 μL. 
     
     
         16 . The microreactor of  claim 1 , comprising polydimethylsiloxane (PDMS). 
     
     
         17 . The microreactor of  claim 16 , wherein the PDMS is bonded to glass, a ceiling of the microchannel comprising the PDMS and a floor of the microchannel comprising the glass. 
     
     
         18 . The microreactor of  claim 17 , further comprising a thin-film heater in contact with the glass.