A novel tool for dynamic cell adhesion studies – the De-Adhesion Number Investigator DANI

Abstract

For an optimal implementation of materials, such as, e.g. medical implants in living environments, a thorough characterization of cell adhesion, kinetics and strength is required, as well as a prerequisite e.g. for bone integration. Here we present a miniaturized (~100 μl) lab-on-a-chip implant hybrid system which allows quantification of cell adhesion under dynamic conditions mimicking those of physiological relevance. Surface acoustic waves are excited and used on optical transparent chips to induce micro acoustic streaming and to create a microfluidic shear spectrum ranging from 0 to ~35 s(-1). We demonstrate its potential for a time-efficient, dynamic screening test of new implant materials using a model of an osseointegration with SAOS-2 cells. The upside-down orientation also allows utilization of the micro reactor on non-transparent materials like titanium and diamond-like-carbon (DLC).

Exploring the Limits of Cell Adhesion under Shear Stress within Physiological Conditions and beyond on a Chip

“…Several groups have already studied cell adhesion under static and dynamic conditions [14,15,16,17,18,19,20]. One of the first approaches to dynamically study cell adhesion used a rotating disk in a fluid above a substrate with adhered cells to generate a shear force field [14].…”

“…However, due to its construction, the method does not allow for in situ observation of the cells, which hinders a detailed time-dependent investigation and high amounts of sample volume are needed in the setup’s recent development stage [15]. In contrast, the technique of surface acoustic wave (SAW)-induced streaming has been shown to enable the construction of much smaller setups to study cell adhesion with respect to shear flow [16,17,18]. Bussonnière et al investigated the de-adhesion of cells directly from a piezoelectric substrate [16].…”

“…We recently developed a SAW-activated system that works with small sample volumes and allows to decouple the single environmental influences from each other. It additionally provides the possibility to observe the cells in situ and to implement arbitrary substrate materials [18]. …”

Characterization of adhesive properties of red blood cells using surface acoustic wave induced flows for rapid diagnostics

“…21 SAWs are an efficient form of ultrasonic wave for on-chip applications, being easily integrated on chip and have been used for particle concentration, 22 manipulation, 23 sorting, 24,25 droplet generation, 26 and mixing. 27 The fluid flows generated using SAW have recently been applied to study cell adhesion, where several cellsubstrate adhesion parameters under physiological conditions were investigated for both single 13 cell-substrate adhesion for healthy, treated, and malariainfected cells suggesting a potential for applying the method for effective diagnosis in remote areas.…”

“…[8][9][10] Previous studies have investigated both static and dynamic conditions that influence shear-stress dependent RBC adhesion to endothelial cells that line the vasculature. Static RBC testing methods investigating molecular mechanisms have utilized both open and closed flow chambers, [11][12][13][14] whereas dynamic testing 15,16 techniques have focused on the kinetics of cell detachment rates by hydrodynamic blood flow forces in micro-channels. These systems commonly require long preparation times and are limited in their ability to study short term adhesion.…”