Abstract: A method for controlling the movement of magnetic or magnetizable objects (10) 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 (20, 30, 30?) for generating a magnetic field with a field gradient substantially perpendicular to the sensor surface (A). The magnetic field generating means (20, 30, 30?) are alternatingly actuated such that the generated magnetic field directs alternatingly the magnetic or magnetizable objects (10) 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.

Abstract: The invention relates to a sensor device (100) and a method for the detection of magnetic particles (1) in a sample chamber (2) with a contact surface (11). The sensor device (100) comprises a sensor unit (120, 130) for detecting magnetic particles (1) in a target region (TR) and/or in at least one reference region on the contact surface. Moreover, it comprises a magnetic field generator (140) 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 (1) 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 (1) under the influence of a magnetic field and the target region (TR).

Abstract: 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.

Abstract: 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.

Abstract: The invention relates to a magnetic sample-processing device, particularly a sensor device (100), that comprises two electromagnets (110, 120) for generating a magnetic field (B) in a first and a second sample chamber (SC1, SC2) located adjacent to each other in an x-direction. The poles of the electromagnets are disposed below the first and the second sample chamber (SC1, SC2), respectively, next to each other in a perpendicular y-direction. Moreover, the electromagnets are individually controlled by a control unit (130). In a preferred embodiment, the distance between the electromagnets (110, 120) 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.

Abstract: 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.

Abstract: 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.

Abstract: Magnetic particles (1) are attracted to a contact surface (11) in an associated sensor device (100) 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 (1) into actual contact with the contact surface (11).

Abstract: The present invention provides a biosensor comprising means (5) 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 (1, 2, 3, 4) adapted to provide a magnetic field gradient at the sensor surface, wherein the unit is arranged below the sensor surface.

Abstract: A method of preparing a sample for a charged-particle microscope includes: Providing a substantially plate-like sample holder having opposed first and second major surfaces substantially parallel to one another, comprising at least one aperture connecting said major surfaces and across which a membrane has been spanned upon said first major surface, which membrane comprises at least one perforation; Spanning a film of liquid across said perforation, which liquid comprises at least one study specimen suspended therein; Plunging the sample holder onto a bath of cryogen, whereby the sample holder is held with said first major surface pointing toward the cryogen and arranged substantially parallel to an exposed surface of the cryogen; and Applying a blast of cryogenic fluid to said film from a nozzle pointing toward said second major surface, immediately prior to the film making contact with said cryogen. A corresponding apparatus is also described.

Abstract: 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.

Abstract: The invention relates to a magnetic sample-processing device, particularly a sensor device (100), that comprises two electromagnets (110, 120) for generating a magnetic field (B) in a first and a second sample chamber (SC1, SC2) located adjacent to each other in an x-direction. The poles of the electromagnets are disposed below the first and the second sample chamber (SC1, SC2), respectively, next to each other in a perpendicular y-direction. Moreover, the electromagnets are individually controlled by a control unit (130). In a preferred embodiment, the distance between the electromagnets (110, 120) 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.

Abstract: The invention relates to a processing device (100) and a method for processing a medium in a processing chamber (121). The processing comprises the addition of magnetic particles (M) to the medium and the mixing of the medium by manipulating said magnetic particles with a time-variable magnetic field (B), particularly a partially oscillating or rotating field. The magnetic field (B) may be generated with a multipole magnetic field generator (110) comprising four subunits (111A,111B), each having a core (113A,113B) with a surrounding coil (112A,112B) and with a top surface (114A,114B), wherein all top surfaces of said subunits are preferably arranged in the same plane and wherein all cores are substantially parallel to each other.

Abstract: A method of preparing a sample for a charged-particle microscope includes: Providing a substantially plate-like sample holder having opposed first and second major surfaces substantially parallel to one another, comprising at least one aperture connecting said major surfaces and across which a membrane has been spanned upon said first major surface, which membrane comprises at least one perforation; Spanning a film of liquid across said perforation, which liquid comprises at least one study specimen suspended therein; Plunging the sample holder onto a bath of cryogen, whereby the sample holder is held with said first major surface pointing toward the cryogen and arranged substantially parallel to an exposed surface of the cryogen; and Applying a blast of cryogenic fluid to said film from a nozzle pointing toward said second major surface, immediately prior to the film making contact with said cryogen. A corresponding apparatus is also described.

Abstract: In a method of performing a cluster assay, a suspension (14) 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 (12) and means for applying a rotating magnetic field (11), the magnetic field being adapted for selectively actuating clusters of superparamagnetic particles. The apparatus further comprises means for detecting the selectively actuated clusters.

Abstract: 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.

Abstract: The invention relates to means for processing a sample fluid containing different components, particularly magnetic particles (M) and targets (cells) (C+M) labeled with magnetic particles. A processing device (100) according to the invention comprises a container (110) with a first compartment (120) that can be filled with a sample fluid and that is separated from a second compartment (130) by a filtering element (140). The filtering element (140) allows the passage of only at least one selected component (M) of the sample. Moreover, an optical surface (150), for example a microscopy slide, is provided in one (120) of the compartments. Components (C+M) of the sample that are in this compartment (120) collect on the optical surface (150). The migration of sample components (M, C+M) is preferably assisted by magnetic fields (B1, B2).

Abstract: 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.

Abstract: The invention relates to means for the examination of a sample, wherein a first input light beam (L1) is totally internally reflected at a detection surface of a sample chamber (111), while a second input light beam (L1?) is transmitted through the sample chamber (111). The resulting first and second output light beams (L2, L2?) are detected and can be evaluated with respect to frustrated total internal reflection and optical absorbance, respectively. Preferably, both output light beams (L2, L2?) are detected by a single image sensor (155).

Abstract: The invention relates to a sensor device (100) and a method for the detection of magnetic particles (1) in a sample chamber (2) with a contact surface (11). The sensor device (100) comprises a sensor unit (120, 130) for detecting magnetic particles (1) in a target region (TR) and/or in at least one reference region on the contact surface. Moreover, it comprises a magnetic field generator (140) 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 (1) 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 (1) under the influence of a magnetic field and the target region (TR).