Despite the increasing importance of next-generation sequencing technologies in laboratory-based DNA analyses, nucleic acid-based testing at the point of care (PoC) still largely relies on DNA amplification methods such as PCR to achieve sufficiently sensitive detection. Over the past decade, significant progress has been made in miniaturizing PCR using microchip technology, pushing PCR out of the lab and into clinical practice. A major shortcoming that is preventing broader uptake of PoC genetic testing is the limited ability for multiplexing. An elegant solution is the use of solid-phase PCR, in which one or both primers are physically tethered to a surface. The PCR product can then be synthesized and detected in a highly localized manner, allowing for simple spatial encoding of amplicon identity combined with high-density multiplexing. This also obviates the need for creating discrete reaction chambers for each separate primer couple and hence complex fluidic routing.
Here we will explore the possibilities of combining imec's state-of-the-art micro-PCR platform and high-precision, low-volume reagent spotting capabilities to enable solid-phase PCR. Different strategies for primer immobilization, primer design and assay chemistry will be compared. Successful multiplex solid-phase PCR will be crucial in the development of PoC genetic tests that can aid in diagnosing infectious diseases with non-specific symptoms (so-called syndromic panels), as is the case for bloodstream, respiratory tract, gastrointestinal, and central nervous system infections. In addition, it will pave the way for developing PoC devices to quickly and cheaply screen extensive panels of mutations that are associated with cancer predisposition and drug response, a key prerequisite for personalized medicine.
Type of project: Internship, Thesis
Duration: 3-9 months
Required background: Biomedical engineering, Bioscience Engineering, Chemistry/Chemical Engineering, Nanoscience & Nanotechnology
Supervising scientist(s): For further information or for application, please contact: Elisabeth Marchal (Elisabeth.Marchal@imec.be)
Imec allowance will be provided