The lack of reliable microvalves impedes many lab-on-a-chip applications for blood analysis. On the other hand, blood clotting — the formation of solid blood aggregate to stop bleeding — provides a natural valving mechanism. It is therefore very attractive to use this mechanism for microfluidic control when blood is available. In fact, the blood clot has many interesting mechanical properties. For example, the fibrin fibers in blood clots have extensibility as high as 330% and an elastic modulus around 8 MPa. However, the study of implementing blood clots as an engineering material, especially in the MEMS area, is lacking.
This work reports the first use of a blood clot as a microfluidic valve. Among several possible means, thermal coagulation is used here to convert blood from liquid into a solid aggregate (i.e., clot), which then blocks the fluidic channel as a closing valve. This work shows that the blood clot valve can have a very simple structure, and can withstand a high differential pressure up to 35 to 48 psig (≈343 to 432 kPa).
Human whole blood was used in this study. For thermal coagulation experiments, a heated water bath was used to induce blood clotting. For pressure testing, 2 pl blood was drawn into a capillary tube (380 pm in diameter) and heated to form the clot. Then a differential pressure was applied by pressurized nitrogen gas with Spsig steps (i.e. Opsig, Spsig, etc. ramping rate l psig/Ssec between steps). Each step was held constant for 20 seconds. The maximum pressure measured before bursting or leaking of the clot was recorded as the threshold pressure.
Interestingly, the threshold pressure [30 to 45 psig (≈308 to 412 kPa)] for a 90 °C temperature is lower than those [55 to 75 psig (≈481 to 618 kPa)] for lower temperatures (70, 75, 80 °C). This can be attributed to excessive dehydration of the clots. Higher heating temperatures produce earlier threshold pressure rising, indicating a shorter heating time is needed. The coagulation time, defined as the minimum heating time for clots to withstand a pressure of 10 psig (≈170 kPa), was also measured. The coagulation time is shorter than one minute for temperatures >70 °C. As expected, longer clots can sustain higher pressures.
The blood clot valve is also realized in a PDMS MEMS (microelectromechanical) chip. Its fluidic channel was initially open. To close the valve, the valve zone was filled with blood and heated to form a clot that blocked the channel. The valve zone was designed to be 50 pm high, 100 pm wide, and 800 pm long. The blood clot uniformly fills the channel after coagulation. Two geometry designs were tested. The results show that designs A and B can withstand pressures up to 35 psig and 48 psig, respectively. This blood clot valve is satisfactory for most microfluidic applications for on-chip blood analysis.