SANOFI-SUPPORTED BIOSTAR SPONSORED RESEARCH PROJECT - 2011
James Harris (Electrical Engineering)
James Zehnder (Pathology)
The pressure of increasing service demands and improving turnaround times of results for patients who need regular examinations requires development of new compact devices for measuring blood components. Existing techniques are well established, but are time-consuming and require highly skilled technicians to perform the analysis in a laboratory environment. Developing miniaturized devices can not only relieve this bottleneck, but also enable a wealth of new therapeutic information as they could be implanted, thus giving real-time information. New optical sensing devices have emerged during the past decade that are based on the measurement of one or more properties of light, such as reflectance, transmittance, absorption, ellispsometry or fluorescence. Photonic crystals (PhCs), which are periodic nanometric optical structures, are the most compact sensors studied so far. PhCs are an attractive sensing platform because they provide strong light confinement due to their photonic bandgap. Light can thus be concentrated in a very small volume leading to a large light-matter interaction, hence increasing the sensitivity of the sensor. PhCs hold the promise to serve numerous sensing applications: environmental, chemical, biological, humidity, gas, vapor, ionic, oil and temperature sensing. The sensing mechanism in PhCs is a refractive index change which can be detected in real-time and does not require the use of markers (label-free biosensing). An added advantage of these nanostructures is that they can be implemented in Lab-on-a-Chip devices for in situ sensing. Because they are fabricated with semiconductor IC like wafer scale technology, they are amenable to very large-scale, low cost production, low-energy consumption and integration with sophisticated signal processing electronics. For the past few years, the Harris lab has been leading the effort to miniaturize and integrate semiconductor-based biosensors for in vivo monitoring of freely moving subjects. Applying this new sensing technology based on PhCs in hematology will open the way for exciting research on blood chemistry at the nano-level.
Prothrombin time (PT) is the method that is used in medical diagnosis to determine the clotting tendency of blood. An estimated 800 million PT assays are performed annually worldwide and while near-patient testing devices are becoming increasingly common, they are still as expensive as the routine laboratory tests. A compact and far less costly device to monitor blood coagulation would have a great impact on the quality of the medical treatment of patients with bleeding disorders. In addition, it is believed that there is a possibility to extract far more diagnostically important information from the clotting curve than simply the clotting time. Thus, having a device that can continuously monitor blood during coagulation would enable an improved understanding of the mechanisms of blood coagulation. Another exciting benefit of using miniaturized devices to study blood coagulation is that they could be implanted, thus giving real-time information during surgery and enabling an improved understanding of the in vivo mechanisms of hemostasis and thrombosis as an extension to the limited knowledge currently available from in vitro tests.
Besides blood coagulation, a compact device based on a new approach for screening Factor VIII (FVIII) is needed. FVIII is a protein that plays a key role in the intrinsic pathway of blood coagulation and its absence in the bleeding disorder, hemophilia A. Hemophilia A is an X-linked genetic disease that occurs in one per 5000-10000 males. Hemophilia A is treated by infusion of plasma-derived FVIII concentrates or recombinant FVIII produced in Chinese hamster ovary cells and baby hamster kidney cells. Plasma-derived FVIII is isolated and refined using several steps to improve purity, immunological and virus safety of the product. These procedures can also give a significant portion of modified or degraded FVIII that has to be identified, characterized and separated. The classical methods to measure FVIII activity are the one-stage clotting and chromogenic assays which are complicated to perform. A sensor that can help monitoring the quality of FVIII concentrates in a rapid and low cost way is thus needed.