Community Research and Development Information Service - CORDIS

Periodic Report Summary 1 - VIRTUALVIALS ("Virtual vials" for enhanced biomolecular analysis)

Virtual Vials is an EID project between Technion and IBM–Zurich, aimed at developing novel tools for biomolecular analysis and training the next generation of scientists and engineers who likely will translate the technologies and discoveries into practical use for the benefit of society and the EU hi-tech sector. In vitro diagnostics is experiencing critical shifts in paradigms with a growing market which encompasses clinical laboratory tests, point-of-care devices, and basic research aimed at understanding the origin of diseases and developing improved testing and treatments. The development of novel tools, which enable increased analysis speeds, higher sensitivity, higher throughput, miniaturization, and portability are essential for enabling discoveries and providing better care for patients. Our project includes three distinct yet synergetic projects for advancing biomolecular analysis. Each project is intended as a PhD project that integrates specific skills and know-how from Technion and IBM. The uniting theme of the projects is the use of microfluidics and isotachophoresis (ITP) to enable precise transport, focusing, and control of samples within micron-sized channels.

Within the first reporting duration of this project, we have made advances in each of the above three projects.

Isotachophoresis-based surface immunoassay: Surface immunoassays (e.g. ELISA, lateral flow) are the gold standard in clinical and point-of-care diagnostics. In contrast to detection of nucleic acid sequences where amplification methods exist, detection of proteins must rely solely on the initial concentration of targets in the sample. Therefore, at low concentrations, immunoassays are limited by the slow binding kinetics between targets and antibodies. We demonstrated the use of isotachophoretic focusing for acceleration of antibody-protein binding kinetics, enabling a significant reduction in limit of detection (LoD) compared to standard immunoassays. Our assay is based on using ITP to deliver the focused sample to a surface functionalized with capture antibodies, where the locally high target concentration boosts the reaction. We distinguish between two modes of operation: continuous ITP, where the sample reacts with the surface while electro-migrating downstream, and stop-and-diffuse ITP, where the electric field is temporarily stopped, enabling longer reaction times.

Delivery of minimally dispersed liquid interfaces for sequential surface chemistry using a microfluidic probe: Delivery of multiple reagents in sequence is central in a large number of surface biochemical assays. For example, protein interactions and function analysis, cell stimulation response, signaling and chemical communication studies, and nucleic acid hybridization- and immuno-assays all require delivery of multiple reagents to a reaction site in a fixed order. We developed a novel method which allows contact-free sequential delivery of reagents to a reaction surface, with a characteristic switching time of 560 ms over a transport distance of 60 cm. The method is implemented on a vertical microfluidic probe (vMFP) — a non-contact scanning device that hydrodynamically confines liquids to a nanoliter-scale volume between an injection and an aspiration channel at its apex. This confined flow can be brought into contact with any surface, including cell tissues, to drive a reaction. Owing to the contact-free operation of the MFP, multiple reaction sites on the surface can be addressed automatically.

Focusing 10 uL into 500 pL - on-chip processing of large volumes using isotachophoresis: A significant limitation of many microfluidics-based diagnostics assays remains their inability to process sufficiently large sample volumes. This is particularly important for cases where the biological target exists at such low concentrations that its presence in the microchannel becomes probabilistic. We developed a novel microfluidic chip capable of focusing a target analyte from sample volumes on the order of 10 uL into 500 pL volumes using isotachophoresis. We demonstrated the potential of this approach for highly sensitive detection of both biomolecular targets (DNA, down to 100 fM) and of discrete targets (whole bacteria, down to 1000 cfu/ml).

Potential outcome of the virtual vials project and economical value:
• In vitro diagnostics is a rapidly growing field and market which encompasses clinical laboratory tests, point-of-care devices, as well as basic research aimed at understanding the origin of diseases and developing improved testing and treatments.
• The 2015 global market for in vitro diagnostics was estimated at $56 billion, and is projected to grow to $75 billion by 2020.
• The development of novel tools, which enable increased analysis speeds, higher sensitivity, higher throughput, miniaturization, and portability are essential for enabling discoveries and providing better care for patients. Within this project, we aim to develop new methods and tools that will enable a new class of highly sensitive point-of-care devices.

Additional information can be found online at http://microfluidics.technion.ac.il/.

Contact

Mark Davison, (EC Programme Coordinator)
Tel.: +972 4 829 3097
Fax: +972 4 823 2958
E-mail

Subjects

Life Sciences
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