Koninklijke Philips Corporation N.V.

Siemens Healthineers Nederland B.v.

Minicare B.v.

Toon Hendrik Evers

Joannes Baptist Adrianus Dionisius Van Zon

Derk Jan Wilfred Klunder

Ron Martinus Laurentius Van Lieshout

Johannes Joseph Hubertina Barbara Schleipen

Jeroen Hans Nieuwenhuis

Mikhail Mikhaylovich Ovsyanko

Wendy Uyen Dittmer

Josephus Arnoldus Henricus Maria Kahlman

Menno Willem Jose Prins

Jacobus Hermanus Maria Neijzen

Marlieke Joan Overdijk

Godefridus Johannes Verhoeckx

Matthias Irmscher

Michaël Franciscus Wilhelmus Cornelis Martens

Wilhelmina Maria Hardeman

Monica Scholten

Maatje Koets

Thomas Johannes Van Gijsel

David Walterus Cornelis Dekkers

Dominique Maria Bruls

Willem-Jan Arend De Wijs

Theodorus Petrus Henricus Gerardus Jansen

Menno W J Prins

Stefan Johannes Hendrikus Toonen

Nicole Henrica Maria Smulders

Bernardus Jozef Maria Beerling

Joost Hubert Maas

Harma Martine Feitsma

Joukje Garrelina Orsel

Josephus Arnoldus Hendricus Maria Kahlman

Kim Van Ommering

Peggy De Kievit

Ricky Kamps

Wilbert Hendrik Bouwman

Joost Lambert Max Vissers

Gwenola Sabatte

Joannes Baptist Andrianus Dionisius Van Zon

Marco Hendrikus Hefti

Eveline Catharina Anna Clasina Den Biezen-Timmermans

Jeroen Hans Nieuwennhuis

Bram De Regt

Martinus Johannes Hieltjes

Wendy U Dittmer

Tom Van Gijsel

Mikhail M Ovsyanko

Marco H Hefti

David W C Dekkers

Michael F W C Martens

Mathias Fournier

Joost L M Vissers

Joukje G Orsel

The invention relates to a method and a sensor device () for evaluating an assay with a sample. During the assay, optical measurements are made at a sensing surface (), and at least one 'homogeneity-image' of the sensing surface () is generated. From this image, an “homogeneity-indicator” is determined for at least one region of interest, and the optical measurements are then evaluated in dependence on said indicator. The homogeneity-indicator may for example be a binary value which indicates if an inhomogeneity was detected or not. If an inhomogeneity was detected, all optical measurements may be rejected, only measurements for the involved region of interest may be rejected, or measurements for a selected sub-area of the involved region of interest (ROI) may be rejected.

Evaluating assays with optical inhomogeneities

An immunoassay for the detection of an analyte in a sample includes a plurality of moieties capable of binding to the analyte. Capture moieties, which are not specific for the same epitope, are bound to a solid substrate, and at least one epitope-specific detection moiety is bound to a detectable marker. The detectable marker is a large particle marker having a particle size of &#x2265;50 nm and &#x2264;5000 nm.

Highly sensitive immunoassay with large particle labels

A device is provided comprising a receiving chamber for receiving a patient's sample, a first reagent reservoir and a second reagent reservoir. The receiving chamber may be configured for receiving at least an end portion of a sample collecting element, with the patient's sample being collected by that sample collecting element. The first reagent reservoir may generally be configured to accommodate a liquid reagent which may include a lysing agent, i.e. the liquid may be a kind of a lysis buffer. Likewise, the second reagent reservoir may generally be configured to accommodate a dry reagent which may include magnetic particles. The device may further comprise at least one of the following two actuators, a first actuator for supplying a first reagent from the first reagent reservoir to the sample and a second actuator for supplying a second reagent from the second reagent reservoir to the resulting mixture.

System for preparing a sample

In order to provide a system allowing an improved and facilitated preparation of a sample for an appropriate analysis, a device for preparing a patient's sample before analysis is provided. The device comprises a housing () and an actuator (). The housing includes a receiving chamber (). The receiving chamber is configured for receiving a liquid. The actuator is movable relative to the housing. The actuator is configured for extracting a predetermined amount of the liquid received in the receiving chamber and for supplying the extracted liquid to a reagent chamber, so that the reagent is suspended in the liquid. The actuator comprises a metering chamber () configured for receiving the predetermined amount of the liquid and for supplying the predetermined amount of the liquid to the reagent chamber.

System for applying a reagent to a sample

A device detects a target molecule in a sample in a sample container to measure the target molecule. A first particle is functionalized with a first binding molecule capable of specifically binding to said target molecule. A surface structure includes a second binding molecule. The surface structure covers a flat sensor or is present on a second particle. The first particle is capable of binding the second binding molecule of the surface structure directly or indirectly. The first and/or second binding molecule is indirectly attached to the particle surface of the first and/or second particle and/or the flat sensor surface via a long and rigid linker molecule. A length and a consistency of the linker molecule is selected such as to result in an average extension length of the linker of more than 60 nm. A number of particle clusters or of bound particles is directly or inversely related to an amount of the target molecules present in the sample.

Long rigid spacers to enhance binding kinetics in immunoassays

Methods for preventing aggregation of detection particles in a test for detecting a multi-epitope target analyte comprising two or more similar or identical epitopes in a sample and/or for determining the concentration of the multi-epitope target analyte in a sample by applying a first capture entity which can specifically bind to at least one epitope on the multi-epitope analyte and block the at least one epitope from binding to a detection particle. The detection of the multi-epitope target analyte may further include the use of a second capture entity, which can specifically bind to the same or a similar epitope of the multi-epitope target analyte as the first capture entity. The multi-epitope target may be detected through the use of a system comprising a sensor surface and the use of a first capture entity to block the at least one epitope from binding to a detection particle.

Reagents, methods and devices to prevent aggregation in particle based tests for the detection of multimeric target molecules

The invention relates to a substance determining apparatus and method for determining a substance within a fluid. Particles attach to the substance and bind to a binding surface (), wherein a particle release curve being indicative of a release of bound particles from the binding surface () is determined, and a part of the particle release curve caused by particles bound to the binding surface via a predefined kind of binding is determined based on the temporal behaviour of the particle release curve. The substance within the fluid is determined based on the part of the particle release curve. The substance can therefore be determined based on particles which are bound to the binding surface via a certain kind of binding, i.e. other kinds of binding substantially do not affect the determination of the substance, thereby improving the accuracy of determining the substance.

System, apparatus and method for determining a substance within a fluid

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

During an assay, optical measurements are made at a sensing surface (), and at least one 'homogeneity-image' of the sensing surface () is generated. From this image, an 'homogeneity-indicator' is determined for at least one region of interest, and the optical measurements are then evaluated in dependence on said indicator. The homogeneity-indicator may for example be a binary value which indicates if an inhomogeneity was detected or not. If an inhomogeneity was detected, all optical measurements may be rejected, only measurements for the involved region of interest may be rejected, or measurements for a selected sub-area of the involved region of interest (ROI) may be rejected.

Concurrently evaluating assays with optical inhomogeneities

The invention relates to a method and a processing device for the processing of a fluid containing interfering particles (C). Magnetic particles (MP) are added to the fluid in a processing chamber and distributed, in part, using a magnetic field to provide a blocking zone (BZ) within the processing chamber to impede or prevent such migration of the interfering particles (C) through the processing chamber. The blocking zone (BZ) hence acts as a filter element by which interfering particles (C) can for example be kept away from a detection region at the surface of the processing chamber.

Processing of fluids containing interfering particles

The invention relates to a filter unit (), a method for manufacturing such a filter unit, and a cartridge () comprising such a filter unit. The filter unit () is characterized in that it comprises a filter material () which is integrated into the aperture of at least one foil (). In a preferred embodiment, the filter material () may be located in the aperture of an intermediate foil () which is embedded between a top foil () and a bottom foil (). Such a filter unit () can readily be produced in cost-effective processes like roll-to-roll manufacturing technologies.

Filter unit for a cartridge

The invention relates to a cartridge () for processing of a liquid sample, for example for the detection of components in a sample of blood. The cartridge comprises a fluidic system with an intake port () leading via an intake capillary channel () to a storage chamber (). Moreover, a feeding capillary channel () leads from the storage chamber () to a detection chamber (). The design of the cartridge () is such that the intake capillary channel () that connects the intake port () to the storage chamber (), has a capillary suction pressure sufficiently high to drive some sample from the intake port to the storage chamber without need of any additional pressure. Furthermore the cartridge a flow control element () adapted to be externally controllable such that the sample can be drawn from the storage chamber () towards the processing chamber () without any active pumping.

Cartridge for fast sample intake

A cartridge for processing a fluid which features a fluid-treatment element that is permeable to at least a part of the fluid, and a processing chamber that is disposed adjacent to the fluid-treatment element. The treated fluid which passes the fluid-treatment element is processed in the processing chamber.

Analysis cartridge with filter unit

The invention relates to an apparatus () and a method for the processing of magnetic particles (MP) provided in a processing chamber () with a binding region () to which said magnetic particles (MP) can (specifically) bind. Removal of unbound magnetic particles (MP) from the binding region () is achieved by first separating them from the binding region () by gravitational forces and then moving them further away by magnetic forces. Gravitational forces can for example be generated by tilting the binding region with a tilting unit (). The prior separation by gravitational forces prevents that unbound magnetic particles (MP) are captured in a cluster with bound magnetic particles.

Processing of bound and unbound magnetic particles

The present invention relates to a cartridge () for the detection of an analyte () in a binding assay with magnetic labels (), the cartridge comprising at least one capture binding agent () against a binding site on the analyte and comprising at least two magnetically labelled tracer binding agents (and) against further different binding sites on the analyte, characterized in that the cartridge comprises at least two regions (and) wherein a first region () comprises the at least one capture binding agent () and a first magnetically labelled tracer binding agent () and wherein a second region () comprises at least one capture binding agent () and a second magnetically labelled tracer binding agent (). Herein the first region () does not comprise a magnetically labelled tracer binding agent other than the first magnetically labelled tracer bind agent () and wherein the second region () does not comprise a magnetically labelled tracer binding agent other than the second magnetically labelled tracer binding agent ().

Binding assay with multiple magnetically labelled tracer binding agents

Growing community of inventors

Eindhoven, Netherlands

Toon Hendrik Evers