Nicolò Manaresi

A lab-on-a-chip for cell detection and manipulation

This paper presents a lab-on-a-chip for electronic manipulation and detection of microorganisms based on the use of closed dielectrophoretic (DEP) cages combined with impedance sensing. A prototype has been realized using a standard printed circuit board (PCB) technology by which polystyrene microbeads have been trapped, concentrated and quantitated, in agreement with CAD simulations, without the need for external optical components. The experiment was successfully repeated with S. cerevisiae. The approach is suited to be implemented in integrated circuit technology, which would allow to manipulate and detect single cells and reduce the system dimension.

Molecular profiling of single circulating tumor cells with diagnostic intention

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.

Electronic sorting and recovery of single live cells from microlitre sized samples

Sorting and recovering specific live cells from samples containing less than a few thousand cells have become major hurdles in rare cell exploration such as stem cell research, cell therapy and cell based diagnostics. We describe here a new technology based on a microelectronic chip integrating an array of over 100,000 independent electrodes and sensors which allow individual and parallel single cell manipulation of up to 10,000 cells while maintaining viability and proliferation capabilities. Manipulation is carried out using dynamic dielectrophoretic traps controlled by an electronic interface. We also demonstrate the capabilities of the chip by sorting and recovering individual live fluorescent cells from an unlabeled population.

A textile based capacitive pressure sensor

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.

Capacitive sensor array for localization of bioparticles in CMOS lab-on-a-chip

Fully-electronic detection of cells and microbeads is achieved on a 320x320 array of capacitive sensors in 0.35/spl mu/m 2P3M CMOS technology that also integrates particle actuation by dielectrophoresis. Particle-associated equivalent input capacitance variations larger than 0.42fF are measured with 39dB SNR. Output noise is /spl les/1.6mV, the resolution of the 12b ADC.

Selective sample recovery of DEP-separated cells and particles by phaseguide-controlled laminar flow

The selective recovery of particles is demonstrated after separation with dielectrophoretic (DEP) forces. Particles are separated based on their size using the so-called cage-speed separation protocol. A two-lane laminar flow enables the selective recovery of the particles. In order to prevent hydrostatic pressure flow, liquid reservoirs are absent. The sample liquid is thus replaced with air during recovery. Phaseguides are introduced in the system to control the liquid–air interface, so that the two-lane laminar flow profile is preserved.

A dynamically reconfigurable monolithic CMOS pressure sensor for smart fabric

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-/spl mu/m 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/.

Lab on a Chip for Live-Cell Manipulation

Precisely manipulating and sorting live cells on a lab on a chip is still a major challenge. This article shows how to use dielectrophoresis for cell sorting. The authors also describe a prototype CMOS chip with a sensor-actuator array, row-column addressing logic and readout circuitry. In this article, we examine the new microelectronic technology that gives scientists the ability to monitor, sort, and analyze vast populations of cells and interact with each cell individually. A microelectronic platform called a lab on a chip (LoC) allows precise manipulation of cells with no effect on their phenotypes. The motivation for developing this technology is that investigations in recent years have shown that a few cells changing their behavior unexpectedly can induce deadly diseases such as cancer. Current LoC design and manufacturing techniques are spawning new biotechnology methods with potential for research, diagnosis, and therapy.

On a road tire deformation measurement system using a capacitive–resistive sensor

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 in it. A strain monitoring method is proposed, which 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 makes it possible to determine the deformation of the tire. Static stress–strain measurements show a linearity of about 80% in the impedance–strain relation. A linear impulse of tensile strain has been used to validate the detection of instantaneous changes in the tread–asphalt interface. The mechanical solicitation resulted in a 1% deformation of the specimens main dimension. Experimental results report a change of about 40% in the real part of the impedance and a change of about 20% in the imaginary part of the impedance. The same measurements have been performed varying the temperature within a range of −20 to 90 °C, which is compatible with the operating conditions of a commercial car tire.

CMOS-only sensors and manipulators for microorganisms

Microelectronics holds the promise to bring to biology the advantages of miniaturization for carrying out highly automated experiments, under software control, with increased speed and low cost. This paper describes an essential building block for this scenario: a method for the stable levitation and independent motion of microorganisms in a liquid and their precise displacement by means of an electronic programmable device.