Polymer nano manufacturing of a biomimicking surface used for kidney stone crystallization studies
Richard Pleeging (TU Delft - Mechanical Engineering)
Urs Staufer – Mentor (TU Delft - Micro and Nano Engineering)
Luigi Sasso – Coach (TU Delft - Micro and Nano Engineering)
Daniel Fan – Coach (TU Delft - Micro and Nano Engineering)
Burak Eral – Coach (TU Delft - Intensified Reaction and Separation Systems)
Gerard Verbiest – Coach (TU Delft - Dynamics of Micro and Nano Systems)
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Abstract
Kidney stone disease is an increasing worldwide issue. There is a current lack of understanding of the exact mechanisms involved, partially due to the need for experimental instrumentation able to mimic the microenvironmental conditions present in vivo. As crystal nucleation often initiates at liquid-solid interfaces, the interface morphology plays a significant role in the rate of nucleation. Within the nephron, the functional unit of the kidney, four distinct segments can be distinguished that contain different surface morphologies. Particularly, the cells lining these segments contain protrusions in the shape of nanopillars that vary in length, diameter and spacing. Exploiting the opportunities provided by organ-on-chip technology, we designed and manufactured a microfluidic device proposed to increase our understanding of the exact mechanisms that drive kidney stone crystallization. We used two-photon polymerization to fabricate surfaces that contain these morphologies in materials possessing a Young’s modulus matching the value of the biological structures. After optimizing design and process parameters like laser power and scanning speed, we manufactured nanopillars with diameters in the range of 150-250 nm and aspect ratios up to 100 with which we can mimic the protrusions in the nephron. Pillar arrays were printed on a glass slide, and assembled with a polydimethylsiloxane (PDMS) microfluidic component (channels 150 um wide). We used high-resolution 3D printing to create master molds used for PDMS soft-lithography. After precise alignment, the two components were brought together and clamped mechanically with a 3D printed holder to ensure a watertight seal between the glass and PDMS. This microfluidic device was used to study crystallization of the most common type of kidney stone, calcium oxalate monohydrate (COM). Because of the chip dimensions combined with a surface morphology this device closely resembles a human nephron.