[Show abstract][Hide abstract] ABSTRACT: Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of > 90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance.
EMBO Molecular Medicine 10/2014; · 7.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A microelectronic chip for the ultra-rapid detection of cells in few micro-liters drop samples is presented. The architecture is based on a two-dimentional 640times480 array of microsites. Dielectrophoresis (DEP) is the physical phenomenon used to manipulate the cells. A corresponding array of photodiodes is used for integrated optical detection. The chip implements a column-parallel, reconfigurable read-out and A/D conversion. The single readout channel is composed by a pre-amplifier with programmable gain and an algorithmic analog-to-digital converter with a 1.5-bit/stage architecture. The chip is implemented in 0.35 mum CMOS technology with a 3.3 V supply.
[Show abstract][Hide abstract] ABSTRACT: This paper describes a wired addressing architecture of distributed sensors for monitoring real-time in situ pressure variations in underwater environment. Limits of isolated sensors and drawbacks of acoustic communication are overcome, and an application to the inspection of a submerged structure is made feasible. The prototype sensor is a Kapton®-based three-layered structure. We fabricated a 0.18 μm CMOS mixed-mode System on Chip (SoC) as a prototype and a five-pad Chip on Board (COB) for unobtrusive monitoring. Testing sessions in aquatic environment have been carried on, and the dependence of the capacitance on pressure variation is shown when a linear pressure variation is exerted. An experimental result in a turbulent operating condition is reported too.
Sensors and Actuators A Physical 08/2006; · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monitoring harsh environments such as underwater scenarios or aircraft external surfaces pertains to important applications like assisted navigation and tactical surveillance; nevertheless, it poses additional challenges compared with standard applications. At Transducers2005 we presented a wired addressing architecture of distributed sensors for monitoring real-time in-situ pressure variations in underwater environment that faces the above-mentioned issues. This architecture consists in a double array of identical and interconnected smart nodes monitoring a matrix of passive sensors. In this paper, we present an analysis of the delay model related to the presented architecture and a calculation of the overall frame-rate of the system as a function of the geometrical topology of the arrays. The topology of the network, i.e. the length of each bus and the number of nodes, can be chosen according to the application, and directly affects the global capacitive load on the serial lines. Each serial line can be schematized with a distributed RC model for the flat cable plus a lumped capacitance for each smart node. Then, a 3rd-order pi-segmented model of O'Brien-Savarino is calculated for a 16-block line with block length equal to 0.3 m. Thanks to that, the global time per iteration is calculated on each bus as well as the scanning time of the whole matrix and the frame rate for the system as a function of sensor distribution and of the aspect ratio of the matrix. This model can be employed to identify the optimal arrangement for the sensor matrix and smart node arrays
[Show abstract][Hide abstract] ABSTRACT: This paper describes a wired addressing architecture of distributed sensors for monitoring real-time in-situ pressure variations in underwater environment. Limits of isolated sensors and drawbacks of acoustic communication are overcome, and an application to the inspection of a submerged structure is made feasible. The prototype sensor is a Kapton<sup>®</sup> based three-layered structure. We fabricated a 0.18 μm CMOS mixed-mode system on chip (SoC) as a prototype and a 5-pad chip on board (COB) for unobtrusive monitoring. Testing sessions in the aquatic environment have been carried out, and the dependence of the capacitance from pressure variation is shown when a linear pression variation is exerted. An experimental result in a turbulent operating condition is reported too.
Solid-State Sensors, Actuators and Microsystems, 2005. Digest of Technical Papers. TRANSDUCERS '05. The 13th International Conference on; 07/2005
[Show abstract][Hide abstract] ABSTRACT: This paper presents a novel approach to continuously measure the mechanical deformations of a tire due to contact with asphalt, by embedding capacitive-resistive sensors on it. A strain monitoring method is proposed, that adopts the tire itself as a sensing element. In this way, the sensing area is pushed towards the tread interface (the part of the tire in direct contact with the asphalt) where the information concerning tire state is actually generated. Tire deformation causes a change of the spacing between the steel wires inside the tire carcass and this change is translated into an impedance change of that region of the tire. By measuring such an impedance change, our approach enables to determine the deformation of the tire. Experimental results supports the feasibility of our approach and are reported and discussed in this paper.
[Show abstract][Hide abstract] ABSTRACT: This paper presents a mixed-signal system-on-chip (SOC) for sensing capacitance variations, enabling the creation of pressure-sensitive fabric. The chip is designed to sit in the corner of a smart fabric such as elastic foam overlaid with a matrix of conductive threads. When pressure is applied to the matrix, an image is created from measuring the differences in capacitance among the rows and columns of fibers patterned on the two opposite sides of the elastic substrate. The SOC approach provides the flexibility to accommodate for different fabric sizes and to perform image enhancement and on-chip data processing. The chip has been designed in a 0.35-μm five-metal one-poly CMOS process working up to 40 MHz at 3.3 V of power supply, in a fully reconfigurable arrangement of 128 I/O lines. The core area is 32 mm<sup>2</sup>.
IEEE Journal of Solid-State Circuits 07/2003; · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper introduces an approach for decoding the pressure information exerted over a broad piece of fabric by means of capacitive sensing. The proposed sensor includes a distributed passive array of capacitors (i.e. an array where no active elements are involved), whose capacitance depends on the pressure exerted on the textile surface, and an electronic system that acquire and process the subsequent capacitance variations. Capacitors can be made in different ways, though, in our demonstrator they have been implemented between rows and columns of conductive fibers patterned on the two opposite sides of an elastic synthetic foam. Measures performed over a prototype has been demonstrated the reliability of the approach by detecting pressure images at 3 F/s and by measuring capacitances as low as hundreds of fF spaced apart at meters of distance.
[Show abstract][Hide abstract] ABSTRACT: This paper presents a mixed-signal system-on-chip (SOC) for
decoding the pressure exerted over a large piece of smart fabric. The
image map of the pressure applied over the fabric surface is achieved by
detecting the capacitance variation between rows and columns of
conductive fibers patterned on the two opposite sides of an elastic
layer, like synthetic foam. The SOC approach allows one to reduce design
time maintaining the flexibility to accommodate for different sensor
sizes and to perform some image enhancement such as fixed pattern noise
compensation and gamma correction. The chip has been designed in a 0.35
μm 5 ML CMOS process to work at 40 MHz, 3.3 V power supply, in a
fully reconfigurable arrangement of 128 rows and columns. The core area
is 32 mm<sup>2</sup>
[Show abstract][Hide abstract] ABSTRACT: Background: Circulating tumor cells (CTC) offer the potential for serially monitoring the molecular profile of a tumor. However, enrichment techniques provide a level of purity problematic for most molecular analysis methods, and do not readily provide for analysis of tumor cell heterogeneity. We evaluate the use of DEPArray™ (Silicon Biosystems), an automated system enabling image-based cell sorting with single-cell resolution, for CTC isolation and characterization from enriched blood samples. Methods: Experiments were carried out with healthy-donor blood (HB) collected in CellSave tubes, spiked with tumor cells (TC) and enriched on Veridex's AutoPrep with the CellSearch ® Epithelial Cell Kit. DEPArray™ system was used for detection and multiple recoveries of single TCs (or control WBCs) and 5 cell batches. A comparison of blind enumeration results with Veridex's CellTracks Analyzer II ® (CTAII) was carried out on replicate samples.