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Simple Summary: A major challenge in the treatment of cancer is predicting patients' responses to anticancer drugs. Thus, preclinical assays that reflect patients' responses to treatments are of utmost importance in clinical oncology and in developing new drugs. 3D tumour models such as spheroids and ex vivo tumour explants are appropriate preclinical models. However, the short-term longevity and low throughput of these models limit their application. To address this, we present a computer-controlled drug screening platform that enables multiplexed delivery of several biochemical reagents such as cellular dyes to 3D tumour models. The platform enables testing up to nine distinct treatment conditions (i.e., nine different biochemical reagents) on more than a hundred 3D tumour models. Moreover, it is compatible with clinical histopathology practice for further manipulation and treatment response analyses of tumour models. Anticancer drugs have the lowest success rate of approval in drug development programs. Thus, preclinical assays that closely predict the clinical responses to drugs are of utmost importance in both clinical oncology and pharmaceutical research. 3D tumour models preserve the tumoral architecture and are cost- and time-efficient. However, the short-term longevity, limited throughput, and limitations of live imaging of these models have so far driven researchers towards less realistic tumour models such as monolayer cell cultures. Here, we present an open-space microfluidic drug screening platform that enables the formation, culture, and multiplexed delivery of several reagents to various 3D tumour models, namely cancer cell line spheroids and ex vivo primary tumour fragments. Our platform utilizes a microfluidic pixelated chemical display that creates isolated adjacent flow sub-units of reagents, which we refer to as fluidic 'pixels', over tumour models in a contact-free fashion. Up to nine different treatment conditions can be tested over 144 samples in a single experiment. We provide a proof-of-concept application by staining fixed and live tumour models with multiple cellular dyes. Furthermore, we demonstrate that the response of the tumour models to biological stimuli can be assessed using the platform. Upscaling the microfluidic platform to larger areas can lead to higher throughputs, and thus will have a significant impact on developing treatments for cancer. [ABSTRACT FROM AUTHOR]

Background: Cancer is the first cause of death in developed countries. The heterogeneous nature of cancer requires patient-specified treatment plans. One reliable approach is collecting Circulating Tumour Cells (CTCs) and using them for prognosis and drug response assessment purposes. CTCs are rare and their separation from normal cell requires high-accuracy methods. Methods: A microfluidic cell capture device to separate CTCs from peripheral blood is presented in this study. The CTC separation device applies hydrodynamic forces to categorize cells according to their sizes. The proposed device is designed and evaluated by numerical simulations and validated experimentally. The simulation modified design was fabricated by soft lithography which allows prototyping the device in a few hours. For experimental setup two solutions: 1) fixed cells spiked in Phosphate Buffered Saline (PBS), and 2) fixed cells in blood were used. The CTC separation device was validated by tracking the flow and separation of cancer cell lines in the solutions. Results: It is demonstrated that the setup is capable of CTC enrichment up to 50 times. Conclusion: The presented CTC enrichment method reduces costs by eliminating the use of antibodies. The high-throughput method has the potential to be used in preclinical studies of cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer drugs have the lowest success rate of approval in drug development programs. In order to address this, predictive preclinical assays that correctly reflect the clinical efficacy of a drug represent an urgent need in both clinical oncology and pharmaceutical research. To address this need, multiple tumor models have been developed, including tumor explant culture platforms, which are the only models that preserve the integrity of the tumor tissue. However, these models have not been fully characterized and multiple variables exist between studies. We investigated the effect of tissue size and culture vessel type on the survival of tumor explants by comparing micro-dissected tumor tissue with corresponding tumor slices. Our results show that the model geometry and culture vessel affect proliferation, apoptosis, and hypoxia in tissue cultures, and must be considered in designing tumor explant culture platforms. Predicting patient responses to anticancer drugs is a major challenge both at the drug development stage and during cancer treatment. Tumor explant culture platforms (TECPs) preserve the native tissue architecture and are well-suited for drug response assays. However, tissue longevity in these models is relatively low. Several methodologies have been developed to address this issue, although no study has compared their efficacy in a controlled fashion. We investigated the effect of two variables in TECPs, specifically, the tissue size and culture vessel on tissue survival using micro-dissected tumor tissue (MDT) and tissue slices which were cultured in microfluidic chips and plastic well plates. Tumor models were produced from ovarian and prostate cancer cell line xenografts and were matched in terms of the specimen, total volume of tissue, and respective volume of medium in each culture system. We examined morphology, viability, and hypoxia in the various tumor models. Our observations suggest that the viability and proliferative capacity of MDTs were not affected during the time course of the experiments. In contrast, tissue slices had reduced proliferation and showed increased cell death and hypoxia under both culture conditions. Tissue slices cultured in microfluidic devices had a lower degree of hypoxia compared to those in 96-well plates. Globally, our results show that tissue slices have lower survival rates compared to MDTs due to inherent diffusion limitations, and that microfluidic devices may decrease hypoxia in tumor models. [ABSTRACT FROM AUTHOR]