BACKGROUND:  Microfluidic technologies have been integrated into many different areas of scientific research, including genomics, proteomics, and enzyme analysis. Commonly referred to as "lab-on-a-chip" technology, microfluidics have helped integrate various processes of a laboratory-such as sample pre-treatment and sample preparation-on a single chip. The miniaturization economizes many laboratory processes due to the reduced consumption of reagents, which leads to the decrease in cost, waste, and time. In spite of the clear advantages of microfluidic devices over macroscale setups, current chip solutions are not well suited for parallel or multi-step syntheses. Individual steps may require changing of solvents, reagents, and conditions, while parallel synthesis may require reactions to be performed using different combinations of reagents. Hence, there is a need for a technology platform that simplifies, accelerates, and diversifies the chemical reactions to further optimize laboratory efficiencies.

INNOVATION:  A research group at UCLA has designed and fabricated a microfluidic chemical reaction circuit (CRC) that can perform multiple in situ click chemistry reactions in parallel. In situ click chemistry produces high-affinity inhibitors of target enzymes through the assembly of building block reagents irreversibly inside a target's binding pockets. Using the technique in conjunction with microchannels, investigators used the technology for the high-throughput screening of an in situ click chemistry library composed of 1,024 independent screening reactions from 16 acetylene and 16 azides.

POTENTIAL APPLICATIONS 

• Lead compound discovery through the parallel screening of an in situ click chemistry library
• Development and production of high-affinity molecular imaging PET probes that target disease-related proteins, yielding excellent signal to background ratios

ADVANTAGES 

• Lead discovery is now convenient, reliable, less expensive, and more diverse
• Low reagent and enzyme consumption
• Precise control over reaction conditions
• Faster reaction kinetics
• Short design/fabrication processes
• Rapid redesign/improvement cycles

DEVELOPMENT TO DATE: Proof-of-concept study has been conducted using both 1st and 2nd generation prototypes. Investigators ran 32 reactions simultaneously on 1st generation CRCs to find inhibitors for a well-known target, bovine carbonic anhydrase-II (bCAII). Investigators have also designed, fabricated, and tested the bCAII click chemistry system using 2nd generation CRCs. They have also demonstrated that this microfluidics device generated the same results as those generated by traditional parallel chemical synthesis and screening methods relying on larger 96-well microtitre plates.

Related Papers (Selected)

• Wang J, Sui G, Mocharla VP, Lin RJ, Phelps ME, Kolb HC, Tseng HR. Angew Chem Int Ed Engl. 2006 Aug 11;45(32):5276-81. (more)

Reference: UCLA Case No. 2005-606 and 2007-570