A Microfluidic Chip for Bio-Bar-Code-Based Detection of Proteins

An ultrasensitive nanoparticle-based biomolecule detection method, known as BioBar-Coding (BBC) was recently developed by the Mirkin Group, which utilizes magnetic microparticle probes (MMP) functionalized with monoclonal antibodies that specifically bind to the target of interest [prostate-specific antigen (PSA) in this case; PSA is a prostate cancer marker and a potential breast cancer marker] and gold nanoparticle probes (NP) coated with both polyclonal antibodies and a distinctive DNA sequence (bar-code DNA), which sandwich the target bound to the MMP. We demonstrate this technique in a single microfluidic device that integrates magnetic separation of the captured target, release of a number of bar-code DNA strands for every target recognition event, and the subsequent detection of the bar-code DNA using a chip-based DNA detection method. PSA concentrations as low as 500 attomolar (~200 target proteins in entire sample and this is four orders of magnitude more sensitive than current PSA assays), using only 1 micoliter total sample volume, were detected in this manner on a single chip.