Menarini Silicon Biosystems, Inc.

Silicon Biosystems S.p.a.

Stmicroelectronics S.r.l.

Consorzio Per La Ricerca Sulla Microelettronica Nel Mezzogiorno

Fraunhofer-gesellschaft Zur Foerderung Der Angewandten Forschung E.v.

Co. Ri. M.me--consorzio Per La Ricera Sulla Microelectronica Nel

Nicolò Manaresi

Gianni Medoro

Alex Calanca

Giuseppe Giorgini

Roberto Guerrieri

Dario Bruno

Marco Tartagni

Biagio Giacalone

Eleonora Franchi

Gerardo Perozziello

Mélanie Abonnenc

Roberto Antonio Canegallo

Maximilian Sergio

Melanie Abonnenc

Rinaldo Poluzzi

Christoph Klein

Vincenzo Matranga

Antonio Gnudi

Giuseppina Simone

Stefano Gianni

Valentina Del Monaco

Paola Tononi

Genny Buson

Giuseppe Sardella

Luigi Altomare

Giovanni Medoro

Antonio Fittipaldi

Michele Rossi

Francesca Fontana

Bernhard Michael Polzer

Christoph Andreas Klein

The present invention relates to a method for the diagnosis of tumoural conditions and/or of the corresponding state of advance, wherein a sample from a patient comprising at least one tumour cell is obtained. According to the invention, a purified specimen of the at least one tumour cell is obtained by individually selecting and isolating single cells in a microfluidic device the purified specimen having a purity of at least 90%. On the purified specimen thus obtained there is subsequently performed a molecular analysis such as to highlight a characteristic thereof suited to enabling diagnosis.

Method for identification, selection and analysis of tumour cells

Method and device () for performing the optical analysis of particles () contained in suspension in a fluid () arranged inside a microfluidic device () which maintains it at a temperature significantly lower than the ambient temperature; the formation of humidity on the outer surface () of the cover of the microfluidic device is avoided by applying a thermal flow (P) which determines an increase in the temperature of the outer surface () of the cover to above the condensation temperature (Td), or reduction in the ambient temperature (and/or humidity) in the vicinity of the cover (), so as to bring the condensation temperature (Td) (dew point) to below the temperature of the surface () of the cover determined by the internal operating temperature.

Method and device for optical analysis of particles at low temperatures

There is disclosed a method of generating a massively parallel sequencing library comprising the steps of: a) providing a primary WGA DNA library (pWGAlib), including fragments comprising a WGA library universal sequence adapter; b) performing a single PCR cycle on the pWGAlib using a first primer (1PR) comprising from 5′ to 3′ a first sequencing adapter (1PR5SA) and a first primer 3′ section (1PR3S) hybridizing to the reverse complementary of the WGA library universal sequence adapter; c) performing a single PCR cycle on the on the product of step b) using a second primer (2PR) comprising from 5′ to 3′ a second sequencing adapter (2PR5SA) different from the 1PR5SA, and a second primer 3′ section (2PR3S) hybridizing to the WGA library universal sequence adapter reverse complementary; d) amplifying by PCR the product of step c) using a third primer comprising the 1PR5SA and a fourth primer comprising 2PR5SA.

Method and kit for the generation of DNA libraries for massively parallel sequencing

A microfluidic device for the isolation of particles of at least one specific type of a sample is described. The microfluidic device comprises: a first inlet adapted to receive a sample comprising the particles of the specific type, at least part of a separation group comprising a separation unit, which comprises a main chamber and a recovery chamber and being adapted to receive the sample and to transfer at least part of the particles of the specific type from the main chamber to the recovery chamber in a selective manner with respect to further particles of the sample, a first outlet which is designed to allow the particles of the specific type to be collected outside of the device and a second outlet adapted to allow at least a portion of the sample to flow out of the main chamber and out of the microfluidic device.

Microfluidic device, microfluidic system and method for the isolation of particles

Methods and apparatus for the selection or processing of particles sensitive to the application of an external stimulus to rupture/lysis at least one selected particle or the fusion of first and second selected particles are disclosed herein. Particles are organized using a first field of force by selectively energizing electrodes of an array of selectable electrodes having dimensions comparable to or smaller than those of the particles. A first configuration of stresses is applied to the electrodes; and then a second configuration of stresses is applied to the electrodes, so as to create a second field of force, located substantially close to at least one selected particle to be lysated or to a pair of first and second particles to be fused and such as to produce the application of a stimulus suited to produce their lysis or fusion.

Methods and apparatus for the selection and/or processing of particles, in particular for the selective and/or optimised lysis of cells

The methods herein can allow for the optimised selection and isolation, within a respective population, of elements of interest and/or utility for a series of subsequent operations. A method can include the phases of: a) identifying, for each particle, at least one of a plurality of characteristic parameters; b) selecting the particles of interest, comparing for each of these the at least one parameter with a respective reference parameter. It can furthermore include the phases of c) storing, for each of the particles, the at least one parameter identified; d) processing the value of a function of the stored parameter, associating the function with a criterion for selection of the particles of interest chosen from a group of possible selection criteria; e) establishing for each particle a threshold criterion to be used as reference parameter. The threshold criterion is established on a time by time basis according to the result of the above processing.

Method and apparatus for the identification and handling of particles

A method for determining the integrity of the genome of a sample and/or the quality of a library of DNA sequences obtained by deterministic restriction site whole genome amplification can include (a) amplifying the library of DNA sequences to produce first, second, and third PCR products each of a different size from 50 bp to 1000 bp, by PCR using at least one first primer pair, one second primer pair and one third primer pair, the primer pairs each hybridizing to a DNA sequence of the library having a length from 1000 bp to 5000 bp and corresponding to a sequence of the genome located respectively on a first, second and third chromosome arm; (b) detecting the first, second and third PCR products; (c) correlating the presence of the first, second and third PCR products with the integrity of the genome of the sample and/or the quality of the library.

Method and kit for determining the genome integrity and/or the quality of a library of DNA sequences obtained by deterministic restriction site whole genome amplification

Method for the treatment of a biological sample comprising at least one cell and a liquid component; according to the method, a force is applied to the sample inserted in an inner chamber of a hollow device towards a filter which has pores with diameters from 2 nm to 1 &#x3bc;m, so that at least part of the liquid component passes through the filter and the cell remains in the inner chamber, thus obtaining a concentrated sample; the filter has a surface facing the inner chamber of less than 12.6 mm.

Devices, apparatus, kit and method for treating a biological sample

The present invention relates to a method for the diagnosis of tumoural conditions and/or of the corresponding state of advance, wherein a specimen of an organic fluid taken from the patient and having a high probability of containing at least one circulating tumor cell (CTC) or a disseminated tumor cell (CTD) is enriched in a population of CTCs or CTDs. According to the invention, at least one type of CTCs or CTDs is isolated by selecting individually single cells in a microfluidic device so to constitute a diagnostic specimen having a purity of at least 90%. On the specimen thus obtained there is subsequently performed a molecular analysis such as to highlight a characteristic thereof suited to enabling diagnosis.

Methods and apparatus are described for the processing particles in which the particles suspended in a first fluid are introduced under laminar flow conditions into at least one first microchamber or first region, in which a second fluid is introduced under laminar flow conditions into at least one second region or second microchamber, in such a way as not to mix with the first fluid, and in which at least one field of force acting on the particles is activated in the microchamber(s), to provoke a shift of the particles alone in a predetermined direction and to transfer the same in suspension into the second fluid.

Method and apparatus for the processing and/or analysis and/or selection of particles, in particular biological particles

A micro-fluidic system comprising a micro-fluidic channel, which has a wall provided with a hole; a closing element, which is partially housed within the hole and has a membrane portion adapted to deform and a side portion sealingly connected with the above mentioned wall; and a partition arranged within the micro-fluidic channel between a first and a second segment; the closing element is deformable between a locked configuration in contact with the partition and an open configuration spaced from the partition; the closing element may be deformed by suction or by a rod or a piston.

Micro-fluidic system

A microfluidic device for isolating particles of at least one given type of a sample; the device is designed to be connected to an apparatus through a plurality of electrical connectors and comprises a system of microfluidic channels and a flash memory, which contains information on the structure (arrangement and geometry of the various components) of the system of microfluidic channels, a map of non-functioning parts of the device, the maximum number of uses and the maximum time of use of the device; the memory has portions allocated for storing the number of times and the time of use of the device.

Microfluidic device for the manipulation of particles

The present invention relates to a method for detecting a first and/or a second target DNA sequence from a DNA library, differing in that a mutation generates/eliminates a restriction site for a restriction endonuclease, comprising the steps of: (a) providing the DNA library, in which each of the DNA sequences comprises a first sequence segment, a second sequence segment of genomic DNA as cleaved by the restriction endonuclease, and a third sequence segment reverse complementary to the union of said first sequence segment and' overhang, if any, of the restriction endonuclease; (b) amplifying the library of DNA sequences by PCR using: a first reverse primer which hybridizes to the 3&#x2032; end region of the second sequence segment of the first or second target sequence positive strand; a second forward primer which hybridizes to the 3&#x2032; end region of the second sequence segment of the first target sequence antipositive strand; a third forward primer comprising a first portion hybridizing to the 5&#x2032; end region of the third sequence segment of the second target sequence antipositive strand and a second portion hybridizing to the 3&#x2032; end region of the second sequence segment of the second target sequence antipositive strand, wherein the first portion of the third forward primer has a length from 20% to 80% with respect to the total length of the third forward primer; (c) detecting DNA sequences amplified in step (b).

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Bologna, Italy

Nicolò Manaresi