Vacuum/Compression Valving (VCV) Using Parrafin-Wax on a Centrifugal Microfluidic CD Platform

This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control.open5

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Non-contact heat management for nucleic acid hybridization in sample-to-answer centrifugal microfluidics

This report focuses on the application of a newly developed non-contact heat management system, based on infrared radiation, to achieve advanced nucleic acid (NA) hybridization on a centrifugal microfluidic platform. Our system was used to eliminate formamide, a common reagent used to enable hybridization at room temperatures. Formamide poses significant challenges in the development of molecular ??TAS platforms with respect to issues such as reagent storage and low analyte detection. Thermal energy can be used to replace formamide during NA hybridization, allowing for the processing of more targets and the elimination of a highly corrosive reagent. The developed heat management system was implemented to produce highly stringent conditions for formamide-free NA hybridization of genetic material from clinical samples containing parainfluenza viruses on a rotating microfluidic platform

Thermo-pneumatic pumping in centrifugal microfluidic platforms

The pumping of fluids in microfluidic discs by centrifugal forces has several advantages, however, centrifugal pumping only permits unidirectional fluid flow, restricting the number of processing steps that can be integrated before fluids reach the edge of the disc. As a solution to this critical limitation, we present a novel pumping technique for the centrifugal microfluidic disc platform, termed the thermo-pneumatic pump (TPP), that enables fluids to be transferred the center of a rotating disc by the thermal expansion of air. The TPP is easy to fabricate as it is a structural feature with no moving components and thermal energy is delivered to the pump via peripheral infrared (IR) equipment, enabling pumping while the disc is in rotation. In this report, an analytical model for the operation of the TPP is presented and experimentally validated. We demonstrate that the experimental behavior of the pump agrees well with theory and that flow rates can be controlled by changing how well the pump absorbs IR energy. Overall, the TPP enables for fluids to be stored near the edge of the disc and transferred to the center on demand, offering significant advantages to the microfluidic disc platform in terms of the handling and storage of liquids.close151