ObjectiveAlthough counting of circulating tumour cells (CTC) has attracted a broad interest as potential markers of tumour progression and treatment response, the lack of functional characterisation of these cells had become a bottleneck in taking these observations to the clinic. Our objective was to culture these cells in order to understand them and exploit their therapeutic potential to the full.DesignHere, hypothesising that some CTC potentially have cancer stem cell (CSC) phenotype, we generated several CTC lines from the blood of patients with advanced metastatic colorectal cancer (CRC) based on their self-renewal abilities. Multiple standard tests were then employed to characterise these cells.ResultsOur CTC lines self-renew, express CSC markers and have multilineage differentiation ability, both in vitro and in vivo. Patient-derived CTC lines are tumorigenic in subcutaneous xenografts and are also able to colonise the liver after intrasplenic injection. RNA sequencing analyses strikingly demonstrate that drug metabolising pathways represent the most upregulated feature among CTC lines in comparison with primary CRC cells grown under similar conditions. This result is corroborated by the high resistance of the CTC lines to conventional cytotoxic compounds.ConclusionsTaken together, our results directly demonstrate the existence of patient-derived colorectal CTCs that bear all the functional attributes of CSCs. The CTC culture model described here is simple and takes <1 month from blood collection to drug testing, therefore, routine clinical application could facilitate access to personalised medicine.Clinical Trial RegistrationClinicalTrial.gov NCT01577511.

Smart integrated miniaturized microsystems require harvesting and storage power sources in order to be autonomous. From the energy point of view, commercially available lithium-ion microbatteries with planar topology do not have suffi cient performance to address the challenging autonomy of microsystems. In aiming for this goal, new concepts based on 3D topologies have been published [ 1 ] in last ten years. By developing a 3D topology, the surface area, and thus the capacity, of the device is increased. The fabrication of high-surfacecapacity devices at the microscale is performed by 1) nano-/micro-structuring a substrate and 2) making a conformal deposition of an electrochemically active thin fi lm on the 3D topology. To achieve conformal deposition on steps and other 3D features, electrodeposition (ED) or highvacuum atomic layer deposition (ALD) are required. The gain obtained with the 3D topology is referred to as the ratio between the 3D and 2D surface areas, and it is known as the area enlargement factor (AEF). The energy density is drastically increased in the 3D topology compared to the planar topology. The power density is also enhanced because the thickness of the 3D deposited material is kept relatively low; the diffusion length of the lithium ions inside the electrode material is reduced, leading to an increase in the charge/discharge rate of the 3D microstorage device.Interdigitated 3D lithium-ion microbatteries based on carbon micro-electromechanical system (C-MEMS) technology with a surface capacity close to 125 µA h cm -2 have been reported [ 2,3 ] by Dunn and co-workers. The micromachining of silicon or glass substrates has been performed by the Peled group [ 4,5 ] in order to fabricate a liquid-based 3D lithium-ion microbattery. Microcontainers fi lled with the battery materials have reached 1 mA h cm -2 under 2 V; the exacerbated surface capacity is clearly enhanced due to the 3D topology. Recently, an interdigitated lithium-ion microbattery based on porous electrodes has been reported with power and energy capabilities greatly enhanced by the 3D porous network. [ 6 ] Simon and co-workers [ 7 ] have developed a nano-architectured aluminum-based 3D metallic current-collector; on top of the 3D nanostructure, a thin layer of anatase TiO 2 polymorph was deposited by ALD. An AEF of 10 is exhibited between the measured 2D and 3D surface capacity. An interesting concept using top-down and bottom-up approaches has been published by Gerasopoulos et al. [ 8 ] using low-aspectratio gold micropillars decorated with biological nano-objects (tobacco mosaic virus, TMV); an enhancement of the surface capacity of a V 2 O 5 thin fi lm deposited by ALD was demonstrated using this novel structure. Previously, Gerasopoulos [ 9 ] et al. reported the ALD of TiO 2 onto biological scaffolds composed of TMV. The TMV nanostructures had been covered beforehand by a nickel conductive layer. The bio-templating approach [ 10 ] has also been used by Kim et al. to fabricate a TiO 2 3D nanonetwork based on peptide assembly; a h...