Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells

Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells

CD-based microfluidics for primary care in extreme point-of-care settings

We review the utility of centrifugal microfluidic technologies applied to point-of-care diagnosis in extremely under-resourced environments. The various challenges faced in these settings are showcased, using areas in India and Africa as examples. Measures for the ability of integrated devices to effectively address point-of-care challenges are highlighted, and centrifugal, often termed CD-based microfluidic technologies, technologies are presented as a promising platform to address these challenges. We describe the advantages of centrifugal liquid handling, as well as the ability of a standard CD player to perform a number of common laboratory tests, fulfilling the role of an integrated lab-on-a-CD. Innovative centrifugal approaches for point-of-care in extremely resource-poor settings are highlighted, including sensing and detection strategies, smart power sources and biomimetic inspiration for environmental control. The evolution of centrifugal microfluidics, along with examples of commercial and advanced prototype centrifugal microfluidic systems, is presented, illustrating the success of deployment at the point-of-care. A close fit of emerging centrifugal systems to address a critical panel of tests for under-resourced clinic settings, formulated by medical experts, is demonstrated. This emphasizes the potential of centrifugal microfluidic technologies to be applied effectively to extremely challenging point-of-care scenarios and in playing a role in improving primary care in resource-limited settings across the developing world

A Modified Consumer Inkjet for Spatiotemporal Control of Gene Expression

This paper presents a low-cost inkjet dosing system capable of continuous, two-dimensional spatiotemporal regulation of gene expression via delivery of diffusible regulators to a custom-mounted gel culture of E. coli. A consumer-grade, inkjet printer was adapted for chemical printing; E. coli cultures were grown on 750 µm thick agar embedded in micro-wells machined into commercial compact discs. Spatio-temporal regulation of the lac operon was demonstrated via the printing of patterns of lactose and glucose directly into the cultures; X-Gal blue patterns were used for visual feedback. We demonstrate how the bistable nature of the lac operon's feedback, when perturbed by patterning lactose (inducer) and glucose (inhibitor), can lead to coordination of cell expression patterns across a field in ways that mimic motifs seen in developmental biology. Examples of this include sharp boundaries and the generation of traveling waves of mRNA expression. To our knowledge, this is the first demonstration of reaction-diffusion effects in the well-studied lac operon. A finite element reaction-diffusion model of the lac operon is also presented which predicts pattern formation with good fidelity

MariaBox: First prototype of a novel instrument to observe natural and chemical pollutants in seawater

The MariaBox project, funded by the European Commission (Contract 614088), is developing an autonomous, analytical device, based on novel biosensors, for monitoring chemical and biological pollutants in sea water. The device, currently at first prototype level, is suitable for installation in free floating devices, buoys or ships. The main, high-level user requirements for the system are for the device to be of high-sensitivity, portable and capable of repeating measurements over a long time, allowing long-term deployment at sea. The first phase of the project, 'user requirements collection', was dedicated to understanding the current needs of water monitoring through institutions in different areas of Europe, at different location types. The locations in which the research was focused are also the ones in which the field validation of MariaBox will take place: a sea water lagoon in Spain with different characteristics of water salinity and natural environment, currently exploited for shellfish farming; a natural site in Ireland (Galway bay); the Skagerrak, a sea arm between Norway, Denmark and Sweden; and a harbour area close to industrial facilities in Cyprus. The analytes of interest for the monitoring institutions are coherent to the list of pollutants to be monitored by the European Commission. A first trade-off between end-user requirements and engineering feasibility, available time and final system cost had to be made. On one hand, the MariaBox device is intended to be portable and its size must be such as to allow permanent positioning inside sea buoys. Several modules are required to achieve the aim of monitoring, in an autonomous and unattended way, all selected target analytes for a period of several months. Energy expenditure is a relevant constraint. Nevertheless, being a device deployed at sea, energy scavenging is a real option to guarantee the system autonomy or, at least, to keep the system operating at a minimum level, that is, to maintain the biosensors and the biochemical reactants in a controlled and safe environment. This controlled environment is managed by the analytical core unit of MariaBox, that acts as a cooler or heater depending on the external temperatures (from-10°C up to +50°C). The system design has been confronted with all of these challenging requirements. The device is intended to provide not only scientific data but also early warnings in relation to both algal blooming and production of toxins, as well as to chemical, man-made pollutants (heavy metals, camphechlor, naphthalene, PFOS). This means that considering the European thresholds for pollutants is not enough. The MariaBox detection capacity has to be under the legal threshold, so as to enable early warnings and the possibility to prevent the pollution with adequate countermeasures. The first MariaBox prototype has been recently produced and is currently being tested and validated in the lab. Within 2017, the device will be replicated and 4 replicas will be installed in the 4 selected pilot locations