Koninklijke Philips Corporation N.v.

Fei Comapny

Minicare B.v.

Mikhail Mikhaylovich Ovsyanko

Toon Hendrik Evers

Derk Jan Wilfred Klunder

Johannes Joseph Hubertina Barbara Schleipen

Joannes Baptist Adrianus Dionisius Van Zon

Ron Martinus Laurentius Van Lieshout

Josephus Arnoldus Henricus Maria Kahlman

Menno Willem Jose Prins

Reinhold Wimberger-Friedl

Wendy Uyen Dittmer

Jacobus Hermanus Maria Neijzen

Jeroen Hans Nieuwenhuis

Anja Van De Stolpe

Arie R Van Doorn

Hervé-William Rémigy

Freek Van Hemert

Andrea Ranzoni

Kasim Sader

Josephus Arnoldus Hendricus Maria Kahlman

Kim Van Ommering

Joannes Baptist Andrianus Dionisius Van Zon

Xander Jozef Antoine Janssen

Ben De Clercq

Karin Smulders-Weemers

Frank Nijpels

A method for controlling the movement of magnetic or magnetizable objects () in a biosensor cartridge. The method comprises the step of providing a biosensor cartridge with a laterally extending sensor surface (A) and at least a magnetic field generating means (') for generating a magnetic field with a field gradient substantially perpendicular to the sensor surface (A). The magnetic field generating means (&#x2032;) are alternatingly actuated such that the generated magnetic field directs alternatingly the magnetic or magnetizable objects () substantially perpendicular to the sensor surface (A) away and toward the sensor surface, wherein pulse lengths of the alternating actuation are adjusted such that a lateral movement of magnetizable objects along the laterally extending sensor surface is substantially avoided.

Pulsed magnetic actuation for sensitive assays

The invention relates to a sensor device () and a method for the detection of magnetic particles () in a sample chamber () with a contact surface (). The sensor device () comprises a sensor unit () for detecting magnetic particles () in a target region (TR) and/or in at least one reference region on the contact surface. Moreover, it comprises a magnetic field generator () for generating a magnetic field that shall guide magnetic particles to the contact surface. With the help of these components, an 'auxiliary parameter' is determined that is related to the magnetic particles () and/or their movement but that is independent of binding processes taking place in the target region between magnetic particles and the contact surface. The auxiliary parameter may for example be related to the degree of mismatch between the positions reached by the magnetic particles () under the influence of a magnetic field and the target region (TR). The evaluation results can be used to validate and/or correct the measurements obtained in the target region (TR).

Sensor device for magnetically actuated particles

A substance determining apparatus determines a substance within a fluid where particles, which have attached the substance, are bound to a binding surface. A sensing unit is configured to generate a sensing signal being indicative of at least one of i) a distance between the particles bound on the binding surface and the binding surface, and ii) an in-plane position of the particles bound on the binding surface. A binding discrimination unit is configured to discriminate between different kinds of binding of the particles bound on the binding surface depending on the generated sensing signal. The binding discrimination unit may be a unit for determining the part of the sensing signal being caused by specifically bound particles and for determining the substance based on this determined part of the sensing signal.

Substance determining apparatus

An apparatus for examination of a sample includes at least one sample chamber in which the sample can be provided, where the sample chamber has a detection surface; at least one light source for emitting a first input light beam which is totally internally reflected at the detection surface of the sample chamber into a first output light beam, and for emitting a second input light beam which is at least partially transmitted through the sample chamber into a second output light beam. The apparatus further includes at least one light detector for detecting the first and the second output light beams. The sample chamber is elongated and traversed in longitudinal direction by light of the second input light beam.

Multiple examinations of a sample

The invention relates to a magnetic sample-processing device, particularly a sensor device (), that comprises two electromagnets () for generating a magnetic field (B) in a first and a second sample chamber (SC, SC) located adjacent to each other in an x-direction. The poles of the electromagnets are disposed below the first and the second sample chamber (SC, SC), respectively, next to each other in a perpendicular y-direction. Moreover, the electromagnets are individually controlled by a control unit (). In a preferred embodiment, the distance between the electromagnets () in x-direction is so large that magnetic cross talk can be neglected. In another embodiment, said distance is close, and the electromagnets are operated in a synchronized way.

Magnetic system for particle attraction in a plurality of chambers

The present invention relates to a method for processing isolated cells, in particular rare cells such as circulating tumor cells, to render them suitable for optical imaging, comprising the steps of (a) depositing filter material comprising captured cells on a phase-change medium; (b) melting said phase-change medium until the medium is spread out below said filter material; and (c) lowering the temperature of said phase-change medium until the medium solidifies, resulting in an optically flat filter comprising said cells at a fixed position. The method may additionally comprise an initial step of capturing a cell on a filter material. The phase-change medium, preferably paraffin wax, may comprise a porous, or mesh-like structure allowing the passage of a fluid through the medium. The phase-change medium may further be mounted on a carrier such as a glass carrier or a polymer material carrier. The present invention further relates to processed filter material comprising isolated cells suitable for optical imaging, which is obtainable by the method; the use of such filter material for diagnostic, histological, microbiological, biochemical, oncologic, or hematologic analysis, as well as a device for isolating cells or processing cells to render them suitable for optical imaging.

Filter support with a phase-changing medium

A biosensor system for the detection of particles includes a biosensor cartridge having a sensor surface. A biosensor magnet assembly is disposed on one side of the cartridge for generating a magnetic field effective at the cartridge and the sensor surface. The biosensor magnet assembly includes at least two magnetic sub-units separated by a gap. A first optical detection system detects the particles arranged at the same side of the cartridge as the magnet assembly. The magnet assembly and the first optical sensor are disposed such that the optical detection is accomplished through the gap of the magnet assembly.

Biosensor system for single particle detection

Magnetic particles () are attracted to a contact surface () in an associated sensor device () by generating a pulsed magnetic field (B) according to an actuation protocol. The protocol includes a 'local attraction phase' during which the duty cycle of the pulsations is smaller than about 10%, preferably ranging between 2% and 5%. These small duty cycles are advantageous in bringing magnetic particles () into actual contact with the contact surface ().

Method and a device for attracting magnetic particles to a surface

The present invention provides a biosensor comprising means () for accommodating a fluid sample having a sensor surface at its bottom and means for detecting particles accumulated at and/or proximate the sensor surface. The biosensor further comprises a quadrupole magnetic unit () adapted to provide a magnetic field gradient at the sensor surface, wherein the unit is arranged below the sensor surface.

Biosensor with quadrupole magnetic actuation system

A method of preparing a sample for a charged-particle microscope includes: A corresponding apparatus is also described.

Preparation of cryogenic sample for charged-particle microscopy

In a method of performing a cluster assay, a suspension () of superparamagnetic particles in a fluid to be analyzed is provided, wherein the superparamagnetic particles are coated with a bioactive agent. The particles are then allowed to form clusters due to an analyte present within the fluid. Subsequently, clusters of superparamagnetic particles are selectively actuated by applying a rotating magnetic field, wherein the amplitude of the magnetic field varies over time. Finally, the selectively actuated clusters are detected. An apparatus for performing a cluster assay comprises means for accommodating a sample () and means for applying a rotating magnetic field (), the magnetic field being adapted for selectively actuating clusters of superparamagnetic particles. The apparatus further comprises means for detecting the selectively actuated clusters.

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Eindhoven, Netherlands

Mikhail Mikhaylovich Ovsyanko