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3D ex vivo Microfluidics Platform

Beyond Limitations: New Microfluidics Platform for Cancer Drug Screening and Profiling

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Need for complex and relevant model systems

As the understanding of complex biological and pathological pathways leading to disease is increasing, so has the need for the complex and relevant model systems arisen to study the mechanisms involved in various disease aspects. Yin X, et al (2016) [19] have aptly described how the model systems (see Figure 2) have been developed across the organismal hierarchy to address specific questions within the realm of biology and medicine.

Within the context of three-dimensional ex vivo platforms, microfluidic technologies have emerged as potentially highly relevant ex vivo tools in cancer research [17, 18]. This rapidly expanding technology relies on the use of small channels equipped to handling small fluids and, therefore, small amount of chemicals and cell material. These platforms have shown to represent physiological relevance over other in vitro technologies, allowing precise control of the cellular, physical and biochemical environment, ability to study cancer-immune interactions, making them a complementary platform for preclinical in vivo models [20].

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3D ex vivo microfluidics platform

The microfluidics system developed by Amsbio in collaboration with researchers at the University of Strathclyde/UK, a miniaturized and high-throughput 3D ex-vivo assay platform, provides a robust, customisable and cost-effective screening system [Mullholland et al, publication under review]. The novel characteristics of this platform enable rapid decision making to prioritize the most promising drug candidates, biomarkers and drug combination strategies for preclinical drug discovery and development.

An advantage of the platform is the ability of cells to form spheroid without the presence of exogenously added matrices/scaffolds to help cells polarize into formation of spheroids. We believe that the endogenously produced ECMs (extracellular matrix, ECM) by cells help polarization and induce cell-contact. This, together with precise fluid control, enables long term culture of spheroids, especially cells derived from patient biopsies or PDXs (Patient derived xenograft, PDX). It has been observed that patient derived primary cancer cells require longer time to form compact spheroids using a standard scaffold free 3D ex vivo technology. However, in our platform we have observed that primary cells form compact spheroids already in less than five days. Therefore, the system enables long-term culture as well as fractionated chemo- and targeted-therapy to study drug efficacy, as well as acquired drug resistance.

The platform has been validated by assessing the efficacy of standard of care compounds against multiple cancer types including glioblastoma, prostate, breast cancer, lung and pancreatic. This platform offers the ability to perform multiparametric end point measurements that include (but are not limited to) viability measurement, changes in spheroid size and shape, assessing the temporal evolution of spheroid response post drug treatment. The system also allows researchers to retrieve spheroids for proteomics and transcriptomics analysis, as well as changes in the spheroid biomarker status using immunohistochemistry techniques (see Figure 3).

In conclusion, Amsbio 3D ex vivo microfluidics platform is well suited for cancer drug discovery, early development and profiling of broad spectrum of molecules including small, targeted and biologics tested against various cancer models.

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