Centre National De La Recherche Scientifique

Institut Pasteur

Université Pierre Et Marie Curie (paris 6)

Ecole Normale Superieure

Other

Sorbonne Université

Institut Pasteur and Centre National De La Recherche Scientifique

Université Paris Diderot-paris 7

Centre National De La Recherche Scientifique-cnrs

Universite Paris Cité

Paris Sciences Et Lettres

Paris Sciences Et Lettres-quartier Latin

Institut Pasteur Centre National De La Recherche Scientifique

Université Pierre Et Marie Curie

University of Portsmouth Higher Education Corporation

David Bensimon

Aaron Bensimon

Vincent Croquette

Jean-François Allemand

Fang-Yuan Ding

Francedillaois Heslot

Fran&ccedil;ois Heslot

Maria Manosas

Xavier Michalet

Jimmy Ouellet

Charles Andre

François Heslot

Gordon Hamilton

Jean-Francois Allemand

Armand Berneman

Arnaud Chiffaudel

Terrence R Strick

Harold Gouet

Jean F Allemand

Danielle Berneman

Paulo Jorge Peixeiro De Freitas

Keith Firman

The invention proposes a device for analyzing nucleic acid molecules (M), comprising: —a bead (), on which one molecule can be anchored at one end, —a surface (), on which the molecule can be anchored at the other end, —an actuator (), adapted to cause the bead to move relative to said surface in one direction, —a sensor (), adapted to measure a distance between the bead and the surface, the device further comprising a well (), having an axis (X-X) extending along the direction of motion of the bead and a bottom () formed by said surface, said well being filled with electrically conductive solution (), and receiving the bead, the sensor being adapted to measure an impedance of the well, depending on a distance between the bead and the surface, to determine, the distance between the bead and the surface.

Device for the analysis of nucleic acid molecules

The invention proposes a device for analyzing nucleic acid molecules (M), comprising: &#x2014;a bead (), on which one molecule can be anchored at one end, &#x2014;a surface (), on which the molecule can be anchored at the other end, &#x2014;an actuator (), adapted to cause the bead to move relative to said surface in one direction, &#x2014;a sensor (), adapted to measure a distance between the bead and the surface, the device further comprising a well (), having an axis (X-X) extending along the direction of motion of the bead and a bottom () formed by said surface, said well being filled with electrically conductive solution (), and receiving the bead, the sensor being adapted to measure an impedance of the well, depending on a distance between the bead and the surface, to determine, the distance between the bead and the surface.

The present invention relates to a method for determining whether a protein binds to a specific DNA sequence. This method is useful in particular for identifying modifications to the DNA sequence (e.g. methylations) via the binding of proteins that specifically recognize those modifications (e.g. antibodies), but also to identify the binding sequence on DNA of a variety of proteins.

Process for detection of DNA modifications and protein binding by a single molecule manipulation

The present invention relates to a method for the determination of a nucleic acid sequence by physical manipulation. In particular, the said method comprises the steps of denaturing a double-stranded nucleic acid molecule corresponding to the said nucleic acid sequence by applying a physical force to the said molecule; and detecting a blockage of the renaturation of the double-stranded nucleic acid molecule. More specifically, the method comprises the steps of denaturing a double-stranded nucleic acid molecule corresponding to the said nucleic acid sequence by applying a physical force to the said molecule; providing a single-stranded nucleic acid molecule; renaturing the said double stranded nucleic acid molecule in the presence of the said single-stranded nucleic acid molecule; and detecting a blockage of the renaturation of the double-stranded nucleic acid.

Method of DNA sequencing by hybridisation

The present invention relates to a fast method for the detection and the quantification of a nucleic acid, DNA or RNA. Specifically, the invention provides a method for detecting and quantifying the presence of a specific nucleic acid molecule which is based on physical and electronic treatments. The method of the invention is particularly useful for applications as diverse as detection of chromosomal abnormal distributions or gene expression analysis.

Method of DNA detection and quantification by single-molecule hybridization and manipulation

The present invention relates to a method for the determination of a nucleic acid sequence by physical manipulation. The method is based on the precise determination of the localization of the replicating fork on the template by measuring the physical distance between one end of the molecule and the fork. This allows the determination of the physical location of the site where a pause or a blockage of the replication occurs, and deducing therefrom information on the sequence of the nucleic acid.

Method of DNA sequencing by polymerisation

Described herein is a method for determining a nucleic acid sequence, said method comprising: a) denaturing a double-stranded nucleic acid molecule corresponding to the said nucleic acid sequence by applying a physical force to the said molecule; b) providing a single-stranded nucleic acid molecule; c) renaturing the said double stranded nucleic acid molecule in the presence of the said single-stranded nucleic acid molecule; and d) detecting a blockage of the renaturation of the double-stranded nucleic acid.

Described herein is a method for determining a nucleic acid sequence, said method comprising: a) denaturing a double-stranded nucleic acid molecule corresponding to the said nucleic acid sequence; b) hybridizing a single-stranded nucleic acid molecule, the primer, with the said denatured double-stranded nucleic acid molecule; c) applying a tension to the hybridized primer/double-stranded nucleic acid molecule obtained in b); d) incubating the hybridized primer/double-stranded nucleic acid molecule obtained in b) with a polymerase in conditions which will lead to at least one pause in replication; and e) determining a position of the said pause in replication with respect to one end of the double-stranded nucleic acid.

The subject of the present invention is a process for aligning a macromolecule (macromolecules) on the surface S of a support, characterized in that the triple line S/A/B (meniscus) resulting from the contact between a solvent A and the surface S and a medium B is caused to move on the said surface S, the said macromolecules having a part, especially an end, anchored on the surface S, the other part, especially the other end, being in solution in the solvent A. The subject of the present invention is also a process for detecting, measuring the intramolecular distance of, separating and/or assaying a macromolecule in a sample in which a process of alignment according to the invention is used.

Process for aligning macromolecules by passage of a meniscus and applications

The invention concerns a method for detecting or locating one or several genes of one or several specific A DNA sequence or one or several molecules reacting with DNA on a B DNA characterised in that it consists in: (a) fixing and combing a certain amount of said B DNA on a combing surface; (b) reacting the product of the B combing with one or several probes, linked with the gene(s) or specific A DNA sequences, or with the molecules capable of reacting with DNA; (c) extracting information corresponding to at least one of the following categories: (1) the position of the probes, (2) the distance between the probes, (3) the size of the probes (the total sum of sizes for quantifying the number of hybridised probes) for determining therefrom the presence, the location and/or the amount of genes or specific A DNA sequences. This method can be used in particular for the diagnosis of genetic diseases.

Method for the diagnosis of genetic diseases by molecular combing and diagnostic kit

A method for detecting or locating one or several genes of one or several specific A DNA sequence or one or several molecules reacting with DNA on a B DNA where the method can include: (a) fixing and combing a certain amount of the B DNA on a combing surface; (b) reacting the product of step (a) with one or several probes, linked with the gene(s) or specific A DNA sequences, or with the molecules capable of reacting with DNA; (c) extracting information corresponding to at least one of the following categories: (1) the position of the probes, (2) the distance between the probes, (3) the size of the probes (the total sum of sizes for quantifying the number of hybridized probes) and determining from this extracted information the presence, the location and/or the amount of a gene(s) or specific A DNA sequences. This method can be used in particular for the diagnosis of genetic diseases.

Physical mapping method using molecular combing technique allowing positioning of a great number of clones within a genome

A product includes a surface on which a coupled complex is aligned, adherent, and stationary, obtained by a process that includes providing a support having a surface with a molecule with biological activity attached, contacting the surface with a sample containing a macromolecule to couple the macromolecule to the molecule on the surface, passing a meniscus over the coupled complex to align the coupled complex, and detecting the macromolecule in the coupled complex. The product is alternatively obtained by passing a meniscus over the molecule with biological activity prior to contacting the surface with a sample containing a macromolecule to couple the macromolecule to the molecule on the surface.

Apparatus for the manipulating and testing of molecules and in particular of DNA comprising a surface on which the molecule is anchored on multiple points at one end and a paramagnetic bead on which said molecule is anchored on multiple points at its other end, magnetic means for applying a force to the bead, said magnetic means being used to control the stretching and rotation of said bead and molecule, optical magnification means and a camera for the visualisation of said bead, computer means to which the images of the camera are transmitted, said computer means comprising means for analyzing the motions of the bead. A method for the manipulating and testing of molecules and in particular of DNA in which a molecule is anchored at one end to a fixed surface and at its other end to a paramagnetic bead wherein said molecule is anchored on multiple points at each of said ends.

Apparatus and method for the manipulation and testing of molecules, and in particular of DNA

A device containing a personalizable substrate associated to a reader allowing the conditional operation of an electric or electronic appliance after comparison of the data with a memory by an identification and comparison circuit located on an essential part of said appliance and methods of using the device under conditional operation of electric or electronic appliances.

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Paris, France

David Bensimon