|Posted by Microfluidic Solutions on December 8, 2012 at 9:20 PM|
MedGadget: In an attempt to miniaturize and speed up testing of large numbers of chemical reactions for potential drug candidates, scientists at UCLA have developed a new microfluidic device capable of performing 1,000 simultaneous in situ click chemistry reactions, which can identify chemicals that bind to proteins. Because enzyme reagents required for in situ click reactions can be costly, the researchers believe their approach may save laboratories money, in addition to time and effort.
Some basics about the chip design from the published article in Lab on a Chip:To reliably produce over a thousand reactions in a single operation, the 2nd-generation microfluidic chip comprises four components: (i) a pair of microfluidic multiplexers31 for regulating the 2 × 16 individually addressed reagent inlets; (ii) a 150 nL rotary mixer for mixing reagents for each reaction; (iii) a 250 nL serpentine channel to accommodate additional PBS to give each reaction the volume (400 nL) required for subsequent manipulation, and to complete the mixing of reagents; (iv) a replaceable 20-cm long poly(tetrafluoroethylene) (PTFE) tube connected to the outlet of the chip to serve as a reservoir for accommodating the reaction mixture slugs emerging from the chip. Following our previous protocol,13 a click chemistry library composed of 8 acetylenes (I–VIII, deployed in duplicate) and 16 azides (1–16) was assembled. Four different types of reaction conditions were tested in parallel to give 1024 individual reaction mixtures. These four conditions are: (i) 128 duplicated reactions with CuI-catalysis to generate reference products; (ii) 128 duplicated reactions between eight acetylene (I–VIII) and 16 azide (1–16) reactants in the presence of bCAII; (iii) 128 duplicated control reactions performed as in (ii) but in the presence of inhibitor 17 to confirm the active-site specificity of the reactions; and (iv) 128 duplicated blank reactions performed as in (ii), but in the absence of bCAII, to monitor catalysis-independent product formation.
Article in Lab on a Chip: An integrated microfluidic device for large-scale in situ click chemistry screening Lab Chip, 2009, 9, 2281-2285