Centrifugally driven microfluidic disc for detection of chromosomal translocations

Abstract

Chromosome translocations are a common cause of congenital disorders and cancer. Current detection methods require use of expensive and highly specialized techniques to identify the chromosome regions involved in a translocation. There is a need for rapid yet specific detection for diagnosis and prognosis of patients. In this work we demonstrate a novel, centrifugally-driven microfluidic system for controlled manipulation of oligonucleotides and subsequent detection of chromosomal translocations. The device is fabricated in the form of a disc with capillary burst microvalves employed to control the fluid flow. The microvalves in series are designed to enable fluid movement from the center towards the periphery of the disc to handle DNA sequences representing translocation between chromosome 3 and 9. The translocation detection is performed in two hybridization steps in separate sorting and detection chambers. The burst frequencies of the two capillary burst microvalves are separated by 180 rpm enabling precise control of hybridization in each of the chambers. The DNA probes targeting a translocation are immobilized directly on PMMA by a UV-activated procedure, which is compatible with the disc fabrication method. The device performance was validated by successful specific hybridization of the translocation derivatives in the sorting and detection chambers.