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Comsol.dk

MEDICAL
MICROVISK TECHNOLOGIES, NORTH WALES, UK
Easy and Accurate Measurement of Blood Viscosity with Breakthrough MEMS-Based Device Simulation-led design has put Microvisk on track to take advantage of the huge home healthcare market when it launches a hand held device that allows individuals to monitor their own blood viscosity quickly, easily and reliably.
BY JENNIFER HAND
The viscosity of blood is widely regard-
ed as an indicator of general health. When a blood vessel is damaged or bro-ken loss of blood needs to be minimized so a series of reactions (known as the clot-ting cascade) begins and a blood clot is formed. A number of medical conditions adversely affect this process and in these cases patients are often prescribed an anti-coagulant such as warfarin. Health management for many of these individu-als involves the weekly monitoring of blood clotting time to ensure that drug dosage is appropriate.
Existing hand held devices work by inducing a chemical reaction which is picked up by electrodes coated with com-pounds, a technology that has not funda-mentally changed in many years. In con-trast, Microvisk has developed a radical new technique that stems from futuristic research on microtechnology and har-nesses the power of Micro Electronic Me-chanical Systems (MEMS). Figure 1. Microvisk's MEMS-based micro-cantilever device.
A Completely Different
passed through the structure each layer aptamer bindings with drugs or antibod- deflects in a different way (Figure 2). As ies, usually utilize crystalline silicon (cSi) Microvisk's MEMS-based micro-cantile- one structural layer expands more, anoth- rigid cantilevers. Because of their rigid- ver devices are produced on a wafer-scale, er expands less, which leads to each can- ity, cSi and similar structures are very where thousands of identical microchips tilever moving up and down in response delicate, brittle and offer restricted move-are processed together as flat structures to immersion in a gas or in a liquid such ment. Although cSi cantilevers can be very on the surface of silicon wafers. Only at as blood. The speed of blood clotting and sensitive, through actuation in resonant the final stage of production are the mi- its rheometric changes associated with mode, the restricted mobility impedes per- cro-cantilevers released to deflect above the clotting process can therefore be moni- formance once these micro-cantilevers or the supporting surface, forming truly 3D tored in a one-stage process based on phys- similar structures such as micro-bridges microstructures (Figure 1). Such highly ics rather than chemistry.
or membranes are immersed in liquids. deformable and flexible micro-cantilevers, Dr. Slava Djakov, inventor and Sen- Through the clever choice of polymer ma- controlled by CMOS (Complementary sor Development Director of Microvisk, terials we enabled the free end of the can-metal-oxide-semiconductor) type signals, explains why Microvisk's approach is tilever to deflect a significantly long way form the heart of Microvisk's unique fluid unique. "Other cantilever designs typical- up from its resting position, which makes micro-probe utilized in determining the ly used in Atomic Force Microscopy (AFM) it extremely efficient and accurate in its rheometric properties of minute (nano- applications or in biological research for response. We can probe for certain param- litre volume) samples. When a current is probing and assessing DNA, protein and eters, for example the viscosity and visco- MICROVISK TECHNOLOGIES, NORTH WALES, UK
Figure 2. COMSOL model showing deflection of the micro-cantilevers.
elastic properties of blood, even at very points? While the standard test interro- multiphysics simulation software began small, sub micro-liter volumes." gates material electronically, we also to appear the company was restrained by By 2004, when the company was found- need to consider mechanical response its small size and limited financing. "We ed and patents were applied for, Micro- and reproducibility and reliability as- had to rely on past experience, basic know visk's research team was quietly confi- pects such as cycling times and perfor- how and gut feeling. Determining the dent about the strength of the technology mance deterioration." design was a long and tedious process in- and its potential for use by ‘consumers' in This calls for an approach combining volving laboratory experiments and real the convenience of their own homes. The both mechanics and statics of beams sys- MEMS solution could be incorporated in a tems with the thermal and electric prop- In 2009 he received the go ahead from hand held device (Figure 3) and the test- erties of structural materials at hand. the Microvisk board and management to ing process was more robust than existing methods. The sample of blood required was tiny and accuracy was greatly im- "We can probe for certain parameters, for example proved. As chemicals were not needed to drive the test there was no shelf life issue the viscosity and visco-elastic properties of blood, and no requirement for strict storage con-trols before, during and after testing.
even at very small, sub micro-liter volumes." Signals, Statistics and Synergy
The very sophistication of the technol- Complexity is further increased when a make the investment required to adopt ogy was also the challenge. "This solu- current is applied to the MEMS structures COMSOL Multiphysics. "They were tion is not so much about how the canti- immersed in and interacting with fluids. focusing on experiments only at first but lever moves up and down," comments Dr A current not only changes electrostatic now acknowledge that it was an excel- Djakov (Figure 4). "It is more about a ho- fields, it also alters mechanical structures lent move to complement the design flow listic approach to integration, packaging and creates thermal effects. Dr. Djakov with simulation. COMSOL Multiphysics and signal processing. The big questions reports that when the research began addresses all the physical properties of a in MEMS-based microchip design, once there was no suitable modeling option and design. This is not easy as we are deal- the concept is proven, are how likely are initially the team was unable to conduct ing with a lot of different parameters: not the chips to perform and what are the set multiple analyses of the MEMS. Then as only are we looking at individual materi- MEDICAL
MICROVISK TECHNOLOGIES, NORTH WALES, UK
Figure 3. Model of hand held device.
"By linking all the physical properties of the design COMSOL has sped up the whole process of iteration, reduced prototyping and shortened development time." als which have their own unique thermal put on the spot to make quick decisions, the device is held against a pricked finger and electric properties, we also have to perhaps without the time and resources to for two seconds the micro capillary draws analyse them when they are tangled to- satisfy all their queries. COMSOL Multi- in the right amount of blood and the result gether. Which materials are the most physics enables us to look at much broader is available 30 seconds later. The patient is critical and how will they behave in the possibilities and decide to investigate two in complete control.
presence of fluid?" or three much further. This means that we COMSOL Multiphysics enables Micro- achieve a better end product at the same A Small Investment;
visk's researchers to see the microchips time as cutting development time." a Huge Potential Return
mechanically, thermally (Figure 5) and Not only has COMSOL Multiphysics en- Point of care testing and home use fig- electro–statically. They can also analyze abled design optimization, it has improved ure highly in the health care strategy of micro fluids and their properties and how the way that the development team com- developed countries. The market is still these interface with the chips and mov- municates with Microvisk's investors. emerging and according to Dr. Djakov the ing cantilevers. "By linking all the physi- Models are easily presented to the board potential for home blood testing is similar cal properties of the design COMSOL has and progress is marked using color maps to that of glucose testing by patients diag-sped up the whole process of iteration, re- nosed with diabetes, a market in which duced prototyping and shortened develop- 160 companies are now established. ment time. We no longer need to solve one Responding to Regulatory
Microvisk plans to launch the new de- problem, then another and plot a graph Requirements
vice in the last quarter of 2011 and is al- after each step," says Dr. Djakov.
With medical diagnostic equipment Previously, data was collected from a there are stringent requirements, for number of prototyping variants of test example, there is a time limit on blood strips then it had to be analyzed, under- sample testing. Blood clotting begins as stood and verified. One iteration typically soon as a finger prick is made so the pro-assessed 20 different design options plus cess needs to be quick. Dr. Djakov is con-the manufacturing and assembly impli- fident that Microvisk has the best possible cations of each. Through modeling with design. "COMSOL Multiphysics has, for COMSOL Multiphysics Microvisk was example, enabled us to create a very good able to start picking out the most prom- solution for the performance of the micro ising options and confirming simulation capillary channel that feeds fluid samples results with laboratory testing. After only onto the microchips." The whole cantilever fifteen months the company had completed is immersed immediately and so the test two major design iterations and a number can begin, with just a quarter of the vol- of optimization refinements and Dr. Dja- ume required by existing test devices. This kov estimates that it had saved four to five means less pain for the patient. In addi- months of development time. "Of course it tion there is no need to take the blood sam- is not as though we would sit and wait for ple to the microchip; and no need to drip Figure 4. Dr. Slava Djakov, Sensor Development
four or five months but scientists would be blood onto a certain part of a device. When Director of Microvisk.
MICROVISK TECHNOLOGIES, NORTH WALES, UK
Figure 5. The COMSOL model shows accurate thermal deflection.
ready working on various add-on features. "Once we launch we will be able to scale up very, very quickly, produce millions of microchips per month and do so cheaply. We know experts are getting very excited  Microvisk is developing a hand held Point of Care and Home Use test for patients because they recognize that changes in who are using anti-coagulant treatments. blood are all driven by changes in vis-cosity. In due course there is nothing to  These devices conduct the internationally recognized Prothrombin Time/ prevent our microchips from performing International Normalized Ratio test by using a drop of the patient's whole blood several tests at once, our technology is taken by a finger prick.
already capable of handling a number of tests on one sample of blood."  The devices are simple to use with a clear display and large buttons. They are With such a large market opportu- comfortable in the hand and the Home Use device is a discreet size. nity, accompanied by low technical risk and a strong intellectual property port-  Microvisk's technology takes a different approach to other devices and tests folio the company expects to break even currently on the market, which use optical analysis or chemical reactions. just one year after the launch of the product. "In terms of development we  Microvisk uses Micro Electro Mechanical Sensors (MEMS) on a disposable strip are right on track," confirms Dr. Dja- which incorporates a small cantilever to measure viscosity. kov. "The situation would be very dif-ferent without COMSOL Multiphysics,  As the devices use a small volume of whole blood the test is less intrusive and which is giving us exactly what we need. removes the need for a laboratory.
Holistic modeling of our technology has made verification of the design much  The Prothrombin Time / INR test works by introducing Tissue Factor to begin a reaction easier for my team. COMSOL Multi- known as the Clotting Cascade. This changes blood from a free flowing solution to a physics and its MEMS module cost only gel-like substance and it is this change that the sensors monitor and detect.
£14,000 yet it has proved to be the best software for us." n

Source: https://www.comsol.dk/story/download/158791/Microvisk_CN2011.pdf