Multiplex SNP genotyping in whole blood using an integrated microfluidic lab-on-a-chip

Pharmacogenetics has often been touted as a cornerstone for precision medicine as detailed knowledge of a specific genetic makeup may allow for accurate predictions of a patient's individual drug response. Still, the widespread use of genetic tests is limited as they remain expensive and cumbersome, requiring sophisticated tools and highly trained personnel. In order for pharmacogenetics to reach its full potential, more cost-effective and easily accessible genotyping methods are desired. To meet these challenges, we present a silicon-based integrated microsystem for the detection of multiple single nucleotide polymorphisms (SNPs) directly from human blood. The device combines a blood lysis chamber, a cross-flow filter, a T-junction mixer, and a microreactor for quantitative polymerase chain reaction (qPCR). Using this device, successful on-chip genotyping of two clinically relevant SNPs in human CYP2C9 gene was demonstrated with TaqMan assays, starting from blood. The two SNPs were detected simultaneously by introducing a sequence of plugs, each containing a different set of primers and probes. The method can be easily extended to detect several SNPs. The microsystem described here offers a rapid, reproducible, and accurate sample-to-answer technology enabling multiplex SNP profiling in point-of-care settings, bringing pharmacogenetics-based precision medicine a step closer to reality.