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Microelectronic Device for Individual Cell Sorting

Objective

Manipulation of single cells is one of the problems that have not been satisfactorily solved for the implementation of labs-on-a-chip. The objective of this proposal is to solve this problem by means of programmable dielectrophoretic force fields, leveraging microelectronic technology to obtain a micro-system with unprecedented flexibility and selectivity. The key expected result is a prototype including a silicon chip and microfluidic add-ons, able to selectively trap single cells of a specific type and move them at will under software control by chip programming. The goal will be reached thanks to the complementary know-how of the participants in the fields of microelectronics and biology.

Manipulation of single cells is one of the problems which has not been satisfactorily solved for the implementation of labs-on-a-chip. The objective of this proposal is to solve this problem by means of programmable dielectrophoretic force fields, leveraging microelectronic technology to obtain a micro-system with unprecedented flexibility and selectivity. The key expected result is a prototype including a silicon chip and micro-fluidic add-ons, able to selectively trap single cells of a specific type and move them at will under software control by chip programming. The goal will be reached thanks to the complementary know-how of the participants in the fields of microelectronics and biology.

OBJECTIVES
The goal of this project is the technological development and the biological validation of a microelectronic device to manipulate and sort biological objects such as single cells in micro-liter volumes. An array of electrodes establishes multiple three-dimensional dielectrophoretic cages by which cells can be trapped and moved individually and independently over the surface of the device under software control. The use of microelectronic technology allows to attain low-cost and enables future integration of other functions such as sensing or heating. The validation of the device on a minute sample of cells, opens biomedical and pharmacological applications in cancer and neuro-sciences that are impractical with existing technologies, such as low-cost and fast biopsy analyses, single cell typing and therapeutic research on rare cells.

DESCRIPTION OF WORK
The project will be carried out following two main action lines:
A1) A microelectronic system based on an integrated array of sensors/actuators that is able to manipulate single cells using superficial electric fields will be analysed and the design methodology explored;
A2) The impact of such device on existing biological cell analysis methodologies will be investigated. The novel device performance will be compared with those of existing assay procedures on a significant biological cell model.
The above action lines will be developed in two time steps:
T1) Design of the microelectronic device: the design will be based on experimental results based on a scaled up prototype and on suitable electromagnetic simulations. Concurrently, while the device is under design, tests on material bio-compatibility in terms of cell viability and the investigations of effects of electromagnetic fields on cells will be performed. Device packaging and micro-fluidics: design and implementation of a watertight chamber with suitable inlet and outlet systems;
T2) Validation of the device as "cell sorter" of closely related lymphocyte populations. More specifically, the selection and the manipulation of rare T-cell populations will be proposed by sorting them on the base of their physical and electrical parameters and, on at second step, by addressing labelled micro-beads on their site for a finest selection. This step will require choice of optimal micro-bead characteristics in terms of physical and chemical parameters and the optimisation of biological parameters such us temperature, cell suspension medium, cell concentration, different cell labelling, fluid characteristics and sample recovery.
Finally, the control of the experiment by comparison with identical higher scale experiments based on a flow cytometer will be performed.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

SILICON BIOSYSTEMS S.R.L.
Address
Viale Giambattista Ercolani 3
40138 Bologna
Italy

Participants (3)

ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA
Italy
Address
Via Zamboni 33
40126 Bologna
COMMISSARIAT A L'ENERGIE ATOMIQUE
France
Address
31-33 Rue De La Federation
75752 Paris Cedex 15
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Address
Rue De Tolbiac 101
75654 Paris Cedex 13