MICRO-BIORHEOLOGY

Macromolecular Dynamics in an Optimized Microfluidic Cross-Slot Geometry: Application to Biofluid Analogues and Prosthetic Fluid Formulation

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 Obiettivo del progetto (Objective)

'Extensional flows occur widely in important biological functions of complex fluids, e.g. blood circulation, respiratory and gastrointestinal mucin flows and the synovial fluid in the joints. Extensional flows can significantly stretch the long-chain molecules present in such fluids, resulting in dramatic increases in flow resistance that are not quantified by standard rheological tests, yet are vital for full characterization of fluid samples. We propose to test the potential of a novel microfluidic chip for performing microfluidic extensional rheology measurements. The chip is based on the classic cross-slot design but has an optimized form so as to provide a pure planar extensional flow of constant strain rate along the exit channels. The novel geometry will be validated through a combination of state-of-the-art experimental techniques performed on model dilute polymer solutions in comparison with numerical simulations using viscoelastic fluid flow models. Subsequently we will use the device to study the extensional flow behaviour of model biofluid analogues based on solutions of well-characterized hyaluronic acid and mucin samples. These long-chain molecules are found in fluids such as synovial fluid and mucus, the flow properties of which can be altered by e.g. over or under expression or degradation of molecular chain length. Such altered rheology of body fluids is associated with conditions ranging from mucositis to cystic fibrosis and arthritis. There will be several outcomes of major importance from this work. Firstly we will be producing a state-of-the-art microfluidic extensional rheometer for testing miniature fluid samples. Second, we will be gaining much needed insight into the development of diseases and leading the way to improved therapeutics and formulation of prosthetic fluids. From a more fundamental perspective, we will be obtaining benchmark data on model biofluids for comparison with future work on healthy and diseased physiological fluids.'

Introduzione (Teaser)

Altered rheology of bodily fluids is associated with numerous pathological conditions. A microfluidic device to measure viscosity of very small samples could pave the way to rapid diagnosis, monitoring and even therapy for osteoarthritis.

Descrizione progetto (Article)

Some materials are sort of stretchy and stringy due to the presence of long and flexible molecules that resist deformation under an applied longitudinal stress. Melted polymers and melted cheese are such materials. So are important biological materials such as saliva, mucus, and the synovial fluid that lubricates and protects cartilage surfaces in mammalian joints.

In arthritis patients, the viscoelasticity of synovial fluid is reduced. A microfluidic platform (a miniature flow channel) developed within the EU-funded project MICRO-BIORHEOLOGY can now characterise synovial fluid undergoing stretching deformations. It could be applied to other fluids as well.

Scientists focused on hyaluronic acid, a polysaccharide found in large quantities in synovial fluid. Hyaluronic acid injections are one treatment for osteoarthritis. Improved understanding will lead to both better diagnosis based on fluid samples and better treatments.

The microfluidic extensional flow device, termed optimised-shape cross-slot extensional rheometer (OSCER), exploits mutually bisecting channels (cross-slots) in order to stretch microscopic fluid samples. The team first confirmed that it accurately reproduces computational fluid dynamics simulations of the flow of simple fluids like water and 'model' viscoelastic fluids of polymers. Using polarised light microscopy on polymer solutions, scientists showed that changes in the intensity of transmitted light are proportional to fluid stress. This makes these changes useful in measuring resistance to extensional deformation (i.e. the extensional viscosity).

Investigators then measured the extensional viscosity of model synovial fluids based on hyaluronic acid solutions. For each fluid tested, the OSCER device measured extensional viscosity up to 50 times higher than the shear viscosity measured by a conventional rheometer. This shows that the synovial fluid 'hardens' in response to strain. In practice, this would mean that it thickens as it is compressed between the joint surfaces, providing shock absorption and preventing damage, particularly from sudden high-load impacts.

Further studies demonstrated that refractive index differences can be used to assess hyaluronic acid molecular properties. This supports the possibility of characterising hyaluronic acid in real synovial fluid to evaluate degradation. The methods could provide the basis for a diagnostic toolbox that could also follow the progression of the disease with biopsy-sized samples of synovial fluid.