Open-volume microfluidic device for manipulation and monitoring of single-cells and tissues

We have previously reported a microfluidic pipette, which combines hydrodynamic flow confinement with solution switching for localized stimulation of single-cells and tissue slices. Some integration challenges still remain, pertaining to size and material properties. Here we present a novel pipette tip fabricated from the photo-polymer SU-8, for which a convenient process was developed, further expanding this technology for single-cell analysis.SU-8 micropipettes were patterned using standard photolithographic techniques and bonded using elevated temperature and high pressure. The fabrication procedure utilizes thermal release tape as a sacrificial layer facilitating release of the microstructures.The micropipettes were tested to withstand pressures between -0.6 and 0.95 bar, while featuring a tip width of only 200 μm. This new micropipette minimizes shadowing in experiments utilising tissue and offers different material composition for single-cell microscopy. The micropipettes have been designed for use in neuropharmacology, cardiac muscle research and for collection of biological substances from single-cells. The high chemical stability of the micropipettes will also allow application in surface chemistry research, for surface patterning with biomarkers and for guided cell growth. We aim to combine this device with THz impedance spectroscopy for monitoring physiological changes in single-cells. We present the first prototype of a millimetre wave coplanar waveguide (CPW), developed with ANSYS HFSS and to be used in combination with the device for single-cell impedance spectroscopy analysis. The CPW will be deposited on an independent glass substrate, separating the cell by a passivation layer. The cells will be exposed to various stimuli using the micropipette. The field of single-cell impedance spectroscopy analysis is at an early exploratory stage, and the combination of microfluidics with THz technology has the potential to bridge the gap between life science and engineering communities