Thermopneumatic suction integrated microfluidic blood analysis system

Abstract

Blood tests provide crucial diagnostic information regarding several diseases. A key factor that affects the precision and accuracy of blood tests is the interference of red blood cells; however, the conventional methods of blood separation are often complicated and time consuming. In this study, we devised a simple but high-efficiency blood separation system on a self-strained microfluidic device that separates 99.7 ± 0.3% of the plasma in only 6 min. Parameters, such as flow rate, design of the filter trench, and the relative positions of the filter trench and channel, were optimized through microscopic monitoring. Moreover, this air-difference-driven device uses a cost-effective and easy-to-use heater device that creates a low-pressure environment in the microchannel within minutes. With the aforementioned advantages, this blood separation device could be another platform choice for point-of-care testing.

Fig 1. Schematic of the self-powered microfluidic device that integrates the functions of blood separation and analysis.

The heating wire is set immediately under the suction chamber. Two dry cells in series constitute the power source.

Fig 2. Cross section of the microfluidic device during operation.

(A) original state; (B) when the heater device starts to heat up the air in the chamber, the number of gas molecules in it decreases gradually; (C) the power is turned off and the whole-blood sample is loaded; (D) the sample is introduced into the channel through atmospheric pressure during the process of cooling down; (E) the whole blood enters the filter trench and the blood cell starts to sediment by gravity; and (F) the filtered plasma can be collected at the outlet of the filter trench. The colored strip on the bottom right side of each image (of the device) is the chromaticity bar, which indicates the temperature variation of the heater device.

Fig 3. Separation efficiency at different depths of filter trench and flow rates.

Fig 4. Separation efficiency with different geometries and results of flow simulation.

Fig 5. Separation efficiencies with different designs of channel.

(A) Separation efficiencies obtained using the buried and suspended channel designs analyzed using flow simulation. (B) Relative positions of the channel and filter trench affect separation efficiency.

Fig 6. Introducing samples into microfluidics by thermopneumatic suction system.

(A) Visible and thermal images of the microfluidic device during heating. The heater device was folded into square-wave-like shape and installed immediately under the suction chamber to effectively heat the air inside the chamber. The red and blue arrows indicate the blood cells and plasma, respectively. The chromaticity bar indicates the temperature from 26°C (room temperature) to 38°C. The system works effectively with relatively small variations in temperature. (B) Chart of temperature reduction inside the chamber, and six actual images inserted near the curves indicate the stages of separation. The chart starts from the cooling down (i.e., from 2 min). The whole-blood sample was sucked into the channel immediately after loading. At 30 s after loading, the sample reached the inlet of the filter trench and filled the entire trench at 6 min. At 8 min, the filtered plasma entered the detection zone, and biomarker examination could be executed immediately.

Fig 7. Comparison between the whole blood and filtered plasma samples on devices with and without a filter trench in the middle of the channel.

The device without a filter trench used whole blood for detection and showed a result with RBC interference. However, the device with a filter trench separated the transparent plasma; thus, the color change can be observed easily and clearly.