title: Multiplex SNP genotyping in whole blood using an integrated microfluidic lab-on-a-chip.
abstract: 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.
authors.affiliation: Department of Life Science Technology, imec, Leuven, 3000, Belgium. Lei.Zhang@imec.be.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Life Science Technology, imec, Leuven, 3000, Belgium. Lei.Zhang@imec.be.
authors.forename: Q
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Life Science Technology, imec, Leuven, 3000, Belgium. Lei.Zhang@imec.be.
authors.forename: R S
authors.initials: RS
authors.lastname: Wiederkehr
authors.affiliation: Department of Life Science Technology, imec, Leuven, 3000, Belgium. Lei.Zhang@imec.be.
authors.forename: M
authors.initials: M
authors.lastname: Fauvart
authors.affiliation: Department of Life Science Technology, imec, Leuven, 3000, Belgium. Lei.Zhang@imec.be.
authors.forename: P
authors.initials: P
authors.lastname: Fiorini
authors.affiliation: Department of Life Science Technology, imec, Leuven, 3000, Belgium. Lei.Zhang@imec.be.
authors.forename: B
authors.initials: B
authors.lastname: Majeed
authors.affiliation: Sensing Technology Research Group, Advanced Research Division, Panasonic Corporation, Kyoto, 619-0237, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsukuda
authors.affiliation: Sensing Solution Development Center, Corporate Engineering Division, Automotive & Industrial Systems Company, Panasonic Corporation, Kyoto, 619-0237, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsuno
authors.affiliation: Department of Life Science Technology, imec, Leuven, 3000, Belgium. Lei.Zhang@imec.be.
authors.forename: T
authors.initials: T
authors.lastname: Stakenborg
mesh_terms: D001769:Blood / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D060005:Genotyping Techniques / Q000295:instrumentation*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D020641:Polymorphism, Single Nucleotide; D018511:Systems Integration
chemical_list: D065729:Cytochrome P-450 CYP2C9