Exploring novel substrates for integrated microscale DNA capture on chip

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Improve medical diagnostics via enhanced scientific understanding of solid phase DNA extraction devices

Point-of-care nucleic acid-based testing offers enormous potential for clinical diagnostics, enabling numerous applications such as accurate detection of infectious disease and prediction of individual drug response. Key factors to success include short time-to-result and ease of use. Crucially, this implies the integration of sample preparation and analysis in a single device. Over the past decade, significant progress has been made in miniaturizing nucleic acid analysis, e.g. using microchips for carrying out quantitative polymerase chain reaction (qPCR). However, advances in on-chip sample preparation have severely lagged behind. One of the main reasons for this discrepancy is the low success rate of transferring standard benchtop protocols to microchips, which typically do not allow large reagent volumes and common sample processing steps such as turbulent mixing and centrifugation. Consequently, efficient on-chip sample preparation requires the development of novel, chip-specific methodologies. One area in need of improved understanding is the binding and release of DNA from the silica surfaces typically used in lab-on-a-chip systems. In this internship, we will explore the potential of solid phase extraction (SPE) methods to achieve optimal binding and release by modulating charge-based interactions between nucleic acids and chip substrate. The student will first build DNA-solid surface interaction model, based on reaction rate kinetics, coupled with a hydrodynamic model of the DNA mass transport to the solid surfaces for SPE in channels of silicon microfluidic devices. The model will be verified by flushing solutions spiked with DNA markers of known concentration at fixed flow rates through the microfluidic channels. The concentration of DNA in the solution before and after flushing and after elution will be measured using qPCR or other techniques to ascertain the amount bound to the silicon microfluidic device. The impact of important variables such as flow velocity on the nucleic acid binding will be explored. Once the model is developed and validated, nucleic acid binding on structures such as micropillar arrays will be investigated. Optimizing the pillar geometry (pillar diameter, pitch, and height) to maximize the binding efficiency and minimize pressure drop is of prime interest. During the internship, it is anticipated that the student will spend approximately 10% of their time on literature review, 60% on analytical and numerical modeling using computational fluid dynamics software such as ANSYS Fluent, and 30% on experimental investigation.

Type of project: Thesis

Required degree: Master of Engineering Science, Master of Science

Required background: Physics, Mechanical Engineering, Chemistry/Chemical Engineering

Supervising scientist(s): For further information or for application, please contact: Ben Jones (Ben.Jones@imec.be)

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