- Federico Paratore
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In the precision diagnostics project, we are creating enabling technologies for healthcare and life sciences using multidisciplinary research and a problem-oriented agenda. Our goal is to solve important medical problems while generating massive amounts of high-value data.
Much of the knowledge we have in biology and medicine is derived from the ability to detect analytes from complex biological samples. In addition, precise analysis of biological samples is vital for diagnostics and managing patients. Therefore, new bioanalytical tools are critically needed to push the frontiers of knowledge in life sciences and to improve healthcare.
Over the years, we have gradually shifted from research on self-assembly, soft lithography and microtechnology to issues in biology and medicine where critical technology gaps exist.
Microfluidics for mobile health
Our current challenges deal with the rapid and precise detection of analytes for point-of-care diagnostics.
We are developing technologies to implement biological assays on microfluidics for point-of-care diagnostic applications. Originally supported by the Swiss Commission for Technology and Innovation (CTI) in partnership with the University Hospital of Basel, this research has now branched out into various directions.
We typically partner with companies and institutions, helping them use our technologies via joint development projects and licensing programs. Our partners are usually from the in vitro diagnostics industry and the semiconductor and MEMS sectors. We also have partners from academic and governmental research institutions within collaborative research projects.
We have pioneered numerous concepts involving capillary phenomena to develop a library of microfluidic functions for implementing biological assays in microfluidics. We have also recently started to integrate solid-state sensors into microfluidics for wearable applications in collaboration with the IBM Watson Research Center in New York.
Our vision is to enable quantitative diagnostics and to connect microfluidic chips to smartphones for fast and convenient analysis of numerous samples. Using smartphones and custom-made peripherals, we recently demonstrated the inclusion of anti-counterfeiting security codes, called “crypto anchors”, in microfluidic devices, a new concept for stop-and-go liquid flow control (“electrogates”), and real-time flow monitoring with sub-nanoliter/second precision.
Furthermore, we believe this technology can generate high-value, critical data for many scenarios involving Watson Health and IBM’s expertise with IT and security platforms.
CAPSYS aims at developing simple-to-use and high-performance microfluidic capillary systems for point-of-care testing. In this project, we exploit the physics of liquids at the microscale, where
- the flow of liquids is typically laminar and predictable,
- small quantities of reagents and samples can be employed, and
- reaction conditions can be optimized using specific microfluidic functional elements.
Programmable hydraulic resistance
To provide an example of a new functional element developed for CAPSYS, we havea implemented a programmable hydraulic resistor in which an array of “electrogates” routes an incoming liquid through a set of resistors to modulate flow rates in microfluidic chips post-fabrication. We showed how we can set flow rate conditions for laminar co-flow of two liquids and monitor an enzymatic reaction in different flow conditions.
Bioassay implementation on chip
Glucose-6-phosphate dehydrogenase (G6PDH) deficiency is an inherited metabolic disorder that affects more than 400 million people worldwide and for which there is a strong need for improvements in point-of-care diagnostic devices. Primaquine, the most commonly used anti-malaria drug, can trigger hemolytic anemia in people with G6PDH deficiency. Therefore, testing for G6PDH deficiency before deciding which drug to administer can save the life of those affected. We have developed a rapid and qualitative assay to determine G6PDH activity and to measure hemoglobin concentration on the same chip from whole blood. We implemented the G6PDH assay in a self-coalescence module, which allows for multiplexing assays in a very small area.
Open space microfluidics
Microfluidic systems are generally “closed”, inside which samples are processed and to which user-to-chip interfaces are established for adding modular functionality. We have developed a scanning, non-contact technology, an example of which is — the microfluidic probe (MFP) — that overcomes key limitations of microfluidics by combining the concepts of microfluidics and of scanning probe. This offers totally new ways to interact with cells and tissues.
Tissue microprocessing for multimodal analysis of tumors
We develop strategies to perform accurate spatial molecular profiling of heterogeneous tumor tissues and cells in culture by selectively studying cells at multiple length scales. The profiling strategies include multi-modal methods to interrogate genomic, transcriptomic and proteomic characteristics of specific sub-populations within heterogeneous samples. These methods are being applied to challenging scenarios often observed in cancer research and diagnostics to evaluate their utility, and eventually translate them to the existing workflows.
Biopatterning and biomolecular responses
We develop new methodology for the efficient and high-quality patterning of biological reagents for surface-based bioassays. By leveraging convective flows, recirculation and mixing of a processing liquid, we overcome limitations of existing biopatterning approaches, such as passive diffusion, uncontrolled wetting and drying artefacts. We aim to facilitate quantitative bioassays, spur the development of the next generation of protein microarrays and by engineering cell-biomolecule interactions, help estimate biomolecular responses.
Scanning probes to localize liquids on surfaces
Techniques to study and locally probe adherent cells & tissues at micrometer distances from cell surfaces in “open space” would represent a major advance for biology at interfaces. To this end, we have developed a non-contact, scanning technology, which spatially confines nanoliter volumes of chemicals for interacting with cells at the μm-length scale. This technology is called the vertical microfluidic probe (vMFP) and shapes liquid on biological surfaces hydrodynamically.
Reconfigurable microfluidics: using a fewer number of “walls”
In this project, we introduce a new concept to break the current paradigm in traditional microfluidics, which makes use of physical channels and mechanical actuators. We strive to democratize microfluidic devices in order to provide a single platform approach towards addressing the requirements of a wide range of applications. We specifically take two approaches: one is leveraging non-uniform electro-osmotic flows, and the other is using purely hydrodynamics.
We use a technique called isoptachophoresis (ITP) to simultaneously separate and preconcentrate analytes based on their effective electrophoretic mobility. ITP is very compatible with miniaturized biochemical analysis systems because it is robust to implement at microscale and can achieve high focusing rates in relatively short channels (order 1 cm). We aim to create “virtual vials” or “compartments” that enable precise transport, focusing and control of samples within micron-sized channels.
Point-of-care diagnostics play a major role worldwide in detecting and treating infectious diseases such as Dengue fever and malaria. Although these devices are typically simple to manufacture and easy to use, they are not exempt from counterfeiting. Simple, classical security features such as product numbers and barcodes or QR codes make them easy targets for forgeries sold on the black market. Crypto-anchors address this challenge by embedding a security code in microfluidic diagnostic devices and “classical” lateral flow tests. This code can be used to identify and link products to highly secured digital transactions on the Cloud and using Blockchain.
Microfluidics for cell research
Cellular assays are used to study how chemicals, biomolecules and factors such as electrical and mechanical stimuli, radiations, and heat affect the viability, metabolism, differentiation, cytoskeleton, motility, adhesion, receptor trafficking, and apoptosis processes of cells. Cellular assays are therefore of fundamental importance in biology, medicine, pharmacology and biotechnology. They are used both at a fundamental research level as well as for diagnostics.
We have developed a method for depositing cell populations in a microfluidic device, stimulating the cells, and creating a biomolecular cascade between the cells. This technology provides scientists a powerful yet flexible method for performing research in the life sciences and helps them pursue the origin of several diseases such as those affecting the human brain.
Collaborations & Funding
We have a longstanding tradition of being innovative and working with academia and industrial partners in collaborative projects. In addition, our project takes advantage of IBM’s profound expertise in science and technology to realize precise diagnostic prototypes, which can be enhanced by IBM’s activities on cloud computing, analytics, the internet of things, security, and mobile health.
Our work has been supported in part by the EU Research projects Chips4Life, e-Gates, CAPSYS, BioProbe, and Virtual Vials. We also received support from a SystemsX.ch project called µFluidXand by the IBM Research Frontiers Institute.
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