by John Williamson
Contributing Editor, MEMS Investor Journal
According to the American Heart Association, atrial fibrillation (AF) is a heart disease affecting some 2.2 million Americans, most of whom are more than 50 years of age. Worldwide estimates range to 6 million patients. Atrial fibrillation is an irregular heart rhythm or arrhythmia caused by an electrical malfunction in the heart itself. This malfunction causes the upper, or atrial chambers, of the heart to quiver or fibrillate, which in turn makes the lower ventricle chambers beat irregularly. While AF shows up on an electrocardiogram, sufferers may exhibit no symptoms. If they do, noticeable palpitations, shortness of breath, fatigue and an uneven pulse may signal the disease. These symptoms may be sporadic.
A risky aspect of AF is that the irregular beating of the heart may cause blood to pool in the heart and form a clot. The clot could dislodge and be transported by the bloodstream to the brain where if blood flow is blocked a stroke may result.
There are several means of addressing AF including anti-coagulant medication to control clotting time, surgery, and catheter ablation. Clotting time is reported as prothombin time (PT). The International Normalized Ratio (INR) is used to measure the effectiveness of blood-thinning (anti-coagulant) medications. A normal INR is 1.0.
Since clotting is a normal function of blood in response to an injury, steps must be taken to reduce the clotting factor through the use of anticoagulants that increase the INR readings – typically to between 2.0 and 3.0 with a target of 2.5. An INR below 2.0 increases the likelihood of clotting in the AF patient’s heart; high readings mean the blood is too resistant to clotting, which could lead to other complications. In any instance, the cardiologist must establish the target INR.
There are several anticoagulants on the market, the oldest of which is warfarin, marketed under the Coumadin and Jantoven brands. New to the market are Rivaroxaban and another anti-clotting agent called dabigatran, with further options expected in the future.
Diet is an important constituent to controlling INR. Because vitamin K can interfere with the blood-thinning effects of Coumadin, patients on the medication must maintain a consistent amount of this vitamin in their diet, typically by avoiding large amounts of green leafy vegetables.
Measuring devices for INR
AF patients on warfarin tablets take a prescribed amount in milligrams on a daily basis. A weekly total is determined on a patient-specific basis. Periodic INR measurements are taken to determine if dosage adjustments are warranted. Measurements can be made at a local healthcare facility on a regular basis such as once a month, or by patients using the measuring device at home. In the latter case, dosage changes are made only by the attending technician after patients call in results.
One INR measuring device is Roche's battery-powered hand-held CoaguChek XS that time and date stamps each test. System components include the meter, packets of test strips each packet with its own code chip, and single use lancets to draw blood. A test strip is inserted into the meter, which then turns on. The lancet is used to procure a blood sample from the patient's finger. The blood sample is carefully applied to the test strip. The INR reading appears in about one minute.
The Roche CoaguChek XS shows an INR of 2.8. Test strips are inserted into the slot at the bottom.
According to Roche, the test provides an electrochemical measurement of prothrombin time following activation of blood coagulation with human recombinant thromboplastin. In simple terms, blood works with the chemicals in the test strip to produce a small electric current in the strip that measures blood-clotting time. The strip itself contains reagent (human recombinant thromboplastin 1.5 units), as well as stabilizers, preservatives, and additives.
Another device is the INRatio Monitor by Alere. According to the company, a test strip is inserted into the monitor and, as with the Roche device, a drop of fresh whole blood is applied. The blood is drawn into the test area by capillary action where it mixes with reagents that cause coagulation to begin. As the blood clots, there is a change in the impedance in the sample.
The Alere test strip showing its components.
The monitor detects the change and then calculates the PT for the sample and reports the result on the screen. It also displays the INR reading along with two quality control tests (normal and therapeutic) simultaneously, and determines whether the controls are within preset limits. If they are, strip integrity is verified, and the monitor reports test results. Otherwise, the monitor displays an error message.
Applying MEMS to INR calculations
UK-based startup company Microvisk has recently announced a new MEMS-based device, now in development, for measuring INR. Rather than using optical analysis or chemical reactions, the Microvisk device uses MEMS sensors on a disposable smart strip incorporating a small cantilever that pulses in the sample to measure viscosity. The sensors monitor and detect the blood changing from a free-flowing solution to a gel-like substance, then display the results in a similar manner to the other devices.
The Microvisk INR measuring device uses MEMS sensors on a disposable smart strip incorporating a small cantilever that pulses to measure viscosity.
According to Microvisk CEO John Curtis, common testing is done using surrogates and relies on thrombin (clotting) generation. He says this is not coagulation but only a part of the coagulation process. "What our process does is work on the blood sample itself by directly measuring coagulation as it happens through the change in the blood's viscosity," he explains.
The Microvisk MEMS-based INR system showing the test strip next to the reader as well as another test strip inserted into the unit.
Curtis says that the normal viscosity of blood is approximately 2 cP, but when coagulating it can become 300 to 400 cP within 100 milliseconds. "Our device will measure this change in real time, displaying the results in 30 seconds. This is something that existing systems cannot do. We're measuring physical, not chemical properties."
In Microvisk's device, a labyrinthine piezo sensor layer is placed between two polyimide outer layers exhibiting different thermal expansion properties. Because the top and bottom layers are of different thickness, their stresses are different. The outer layers have heaters powered by the unit's self-contained batteries. These apply a 600 µs heat pulse of approximately 40˚C evenly across both strips to a 5 µL blood sample. Viscosity is determined by measuring the output from the piezo sensor as the strip goes down and then when it springs back up. Curtis reports that the MEMS-based strips will be competitively priced with those used with conventional INR measuring devices.
Surgical processes enabled by MEMS devices
In addition to INR measuring devices, surgical processes are also employed to control the abnormal electrical activity causing AF. The goal of such surgeries is to create lesions in the heart wall. This is done by invasive surgery -- generally as part of another surgical process or by a less invasive ablation catheter using radiofrequency waves to create the lesions.
However, conventional catheter ablation has the disadvantage of surgeons being unable to measure the correct force to be applied in creating the lesions. If the applied force is too small, the treatment may be ineffective; too much force can cause a perforation in the heart wall.
By employing MEMS technology, Geneva-based Endosense has developed a force-sensing ablation catheter called the TactiCath that provides surgeons a real-time measure of the force being applied to create the lesions.
The Endosense TactiCath steerable ablation catheter is equipped with a fiber optic force sensor in the tip that provides real-time accurate force and angle measurements between the catheter itself and the heart wall.
The system consists of a 2.3 mm irrigated steerable ablation catheter equipped with a fiber optic force sensor in the tip that provide real-time accurate force and angle measurements between the catheter itself and the heart wall. The complete tip contains fiber optics, RF and the saline solution delivery system. Through it, physicians can achieve accurate force measurements. Monitor-displayed measurements are provided at 100 ms intervals.
Copyright 2011 MEMS Investor Journal