Capillary microfluidic chip with integrated pump and valve actuator
Glycated Hemoglobin (HbA1c) is a long-term blood glucose marker currently only available by laboratory testing. Main hurdle for point-of-care testing of HbA1c is the necessary on-chip sample preparation. One limiting factor is the lack of miniaturized, time-controlled liquid actuation functionalities. Thus, an electrochemical pumping has been used for the required flow control. In contrast to previous works the sample is directly used as working liquid for pumping and valving. Differently to e.g. a novel gel-based check valve approach is employed to avoid undesired liquid movement towards the inlet of the chip. This method results in a miniaturization of the chip design and sample volume, the combination of passive and active microfluidics and the elimination of external handling steps and additional reagents.
Concept: Dry hydrogel valving approach
The intended microfluidic sequence to be performed by the chip includes capillary sample uptake and the pumping of an exactly defined and minimized volume (5 µl) into a preset analyzing channel (Fig. 1). After capillary filling of the inlet channel and the valve reservoir the dried super absorber swells due to contact with the sample and forms a gel. Subsequently the gel (swollen super absorber) is pushed into the channel by electrolysis to form a check valve at an adjustable time. In the next step the sample is further pushed towards a measuring chamber by a second electrolysis actuator which is placed downward in the inlet channel. The gel valve avoids liquid movement towards the inlet. The described actuation concept was transformed by a layout jointly developed by Fraunhofer ENAS and Senslab GmbH.
Fabrication of the microfluidic chip
The polymer chip consists of a transparent, hot embossed channel layer (polycarbonate) and a metalized bottom layer (gold on polycarbonate) for electrode integration. The chip dimensions are 39 mm x 6 mm. The fabrication steps include PVD-coating, laser structuring of the electrodes, hot embossing and laser welding. Gold as the electrode material was deposited on a black polycarbonate foil by PVD. Afterwards, the electrodes were micro structured by laser ablation. The microchannel substrate was fabricated by hot embossing by our partner institute Fraunhofer IWU.Before joining the hot embossed part and the electrode part a small amount of hydrogel was applied inside the valve reservoir. The gel was subsequently dried to obtain a well-localized super absorbing material for swelling during usage.
As final step laser contour welding was employed to join the two layers. Therefore, a continuous 20 W IR-fiber laser with attached scanner system and a spot size of 50 µm was used. The thermal influence of the laser beam is limited to the welded structures with only minor thermal effects in the surrounding material. This allows the integration of a (temperature sensitive) biochemical coating before joining. Only for the sealing of the electrode areas small adhesive tapes were used, since laser welding would result in the destruction of the electrodes.
The whole process flow was tested with distilled water and human capillary blood as sample medium.
The experiments showed that both liquids are useable for gel formation. If distilled water is used, however, a small amount of super absorber is sufficient for swelling and building up a valve. With growing number of ions in the medium (such as for blood) the amount of super absorber has to be increased.
Conclusion and acknowledgment
A microfluidic chip combining capillary and active flow control has been developed. The chip uses a novel approach for electrochemical pumps based on hydrogel swelling and electrolysis. Inlet sealing is carried out “on-chip” by an innovative valving concept. The functionality of the novel approach has been demonstrated for distilled water and capillary whole blood.
This presented work was performed in the project GlykHbLab (FKZ V4MOD023) funded by the German Federal Ministry of Education and Research.