Koninklijke Philips Corporation N.v.

Asml Netherlands B.v.

Medimetrics Personalized Drug Delivery B.v.

Medimetrics Personalized Drug Delivery, Inc.

Stoco 10 Gmbh

Biocartis, Nv

Anke Pierik

Johan Frederik Dijksman

Jeff Shimizu

Hans Zou

Sander Frederik Wuister

Reinhold Wimberger-Friedl

Frits Tobi De Jongh

Judith Margreet Rensen

Martin Maurice Vernhout

Yvonne Wendela Kruijt-Stegeman

Michel Gerardus Pardoel

Ivar Schram

Ruud Vlutters

Marius Iosif Boamfa

Fei Zuo

Antonius Johannes Joseph Wismans

Remus Albu

Marc Van Driel

Derk Jan Wilfred Klunder

Pieter Jan Van Der Zaag

Roelof Koole

Lucian Remus Albu

Hendrik Roelof Stapert

Hans Marc Bert Boeve

Marinus Bastiaan Van Leeuwen

Willem-Jan Arend De Wijs

Bas Hulsken

Jelte Peter Vink

Richard Joseph Marinus Schroeders

Derk J W Klunder

Pieter Klaas De Bokx

Sieglinde Neerken

Ventzeslav Petrov Iordanov

Marinus Bastiaan (Rien) Van Leeuwen

Johannes Theodorus Wilhelmus Maria Van Eemeren

Koen De Laat

Olaf Weiner

Henk Van Damme

Martijn Van Zelst

Rene Bakker

Antonius Johannes Jo Wismans

Adrianus Theodorus Anthonius Maria Raaijmakers

Leonardus Johannes Cornelius Van Den Besselaar

Petrus Leonardus Adrianus Van Der Made

Danielle Elisa Willemine Clout

Reinhold Wimburger-Friedl

Johan Gerard Kleibeuker

Claude Jean-Marie Malaurie

Yvan O J G Droinet

Irene Johanna Monia Dobbelaer-Bosboom

Judith Margaret Rensen

Martinus Johannes Van Zelst

Reinhold Wimberger-friedl

Bernadet Dagmar Marielle Meijering

Richard J M Schroeders

Antonius J J Wismans

Leonardus J C Van Den Besselaar

Adrianus T A M Raaijmakers

Currently, there is interest in applying machine learning techniques to analyse digital pathology images automatically. Machine learning techniques often rely on training with a ground-truth image input. The quality and amount of training data determines the quality of the detector, as expressed in the rate of true and false positives, and robustness against variations in the appearance of the input images. The present application proposes to obtain image data of the same sample before and after at least one re-staining step (firstly with a structure-revealing stain, and secondly with a bio marker revealing stain). Sections of the first and second image data having a good registration relationship are chosen, along with the probability of detecting a desired candidate object (such as nucleus) and the probability of the bio marker revealing stain being present annotation data suitable for training a machine learning algorithm on the first and/or the second image data is provided.

Generating annotation data of tissue images

The invention relates to a printing control device () to control printing of a cover layer on a tissue or cell sample to be examined, a system () for printing of a cover layer () on a tissue or cell sample to be examined, a method to control printing of a cover layer on a tissue or cell sample to be sample to be examined, a computer program element for controlling such device or system for performing such method and a computer readable medium having stored such computer program element. The printing control device () comprises an imaging unit () and a printing control unit (). The imaging unit () is configured to provide image data of the sample, and to determine a local image parameter from the image data. The local image parameter relates to local tissue porosity and/or a local capillary force of the sample. The printing control unit () is configured to control a printing parameter for printing the cover layer on the sample based on the local image parameter.

Printing control device to control printing of a cover layer on a sample

The present invention relates to an illustration of an annotation () at a sample slide (). It is the intention for the invention to copy the annotation () provided at a reference slide () to the sample slide (). Typically, a reference image () of the reference slide () is provided, in particular by scanning the reference slide (). The reference image () therefore has the information about a reference slice () which is carried by the reference slide (). Furthermore, the reference slide () has been marked with a region of interest () and the annotation (), which can be associated with the region of interest (). If such reference slide () is scanned, the respective reference image () comprises the information about the marked region of interest () as well as the annotation (), too. Furthermore, the sample slide () carrying a sample slice () can be scanned, in order to provide a sample image (). The sample slice () and the reference slice () are cut from the same object () of a biological material. In particular, the sample slice () has been cut directly after a cut of a material block has been preformed to provide the reference slice (). Since the reference slice () and the sample slice () are from the same object (), their features are very likely that the reference image () and the sample image () are very similar. Due to this similarity, the annotation () of the reference slide () is copied on a basis of an image recognition between reference image () and the sample image () to the sample slide ().

Information transformation in digital pathology

A method is presented that enables the spatial mapping of nucleic acids of tissue samples with high resolution and without sacrificing the degree of multiplexing that is available from next-generation sequencing. The method is based on the application of patterns of barcoded oligonucleotides probes onto predefined locations in a region of interest in a tissue sample. Every nucleic acid analyzed can be allocated to a certain position inside the sample based on the barcode. Various printing technologies can be used and different ways of patterning can be employed, like a regular array with a certain pitch or alternatively an object-based patterning with defined regions of interest without shape constraints.

Spatial mapping of molecular profiles of biological tissue samples

The present invention relates to digital pathology. In order to improve the workflow in the process of selecting a region of interest of an unstained sample to be removed for molecular diagnostic, a method () is provided for selecting a sample removing area of an unstained sample to be removed for molecular diagnostic. The method comprises the following steps: In a first step, also referred to as step a), a reference removing area is selected in a reference image of a reference slice of an object, wherein biological material in the reference slice is stained. In a second step, also referred to as step b), a digital sample image of a sample slice of the object is obtained under an imaging setting. The biological material in the sample slice is unstained. The sample slice is received on a sample slide and positioned in an optical path between a light source and an image detector. In the optical path between the light source and the image detector, it is further provided a contrast enhancing arrangement for improving contrast between the unstained biological material and background. Light is provided passing through the sample slice to be received by the image detector. In a third step, also referred to as step c), the digital sample image is registered with the reference image for translating the reference removing area in the reference image to the digital sample image. In a fourth step, also referred to as step d), a sample removing area is identified in the digital sample image based on the translated reference removing area.

Digital pathology system

The present invention relates to digital pathology. In order to facilitate analyzing a tissue microarray, an apparatus is provided for tissue examination. The apparatus comprises a data input (), a tissue microarray analyzing unit (), and an output (). The data input is configured to receive a reference image of a reference slice obtained from a tissue sample block; and to receive a microarray image of a microarray slice comprising at least one tissue core obtained from at least the tissue sample block. The tissue microarray analyzing unit is configured to register tissue core images of at least one tissue core with the reference image based on a spatial arrangement of the respective tissue core within the tissue sample block. The output is configured to provide a registered result obtained from the tissue microarray analyzing unit for further analyzing purposes.

Tissue microarray registration and analysis

A device () and a method optically control a chemical reaction in a reaction chamber () holding a reagent fluid (). The chemical reaction includes a nucleic acid sequencing on a wiregrid. Based on strong optical confinement of excitation light () and of cleavage light (), the sequencing reaction can be read-out. Stepwise sequencing is achieved by using nucleotides with optically cleavable blocking moieties. After read-out the built in nucleotide is deblocked by cleavage light through the same substrate. This ensures that only bound nucleotides will be unblocked. In order to avoid overheating by cleavage light, the reagent fluid is circulated along the surface of the substrate ().

Optical controlling of a chemical reaction

The invention relates to a fluidic system comprising at least one bead chamber () containing a lyophilized reagent (LB) and a reaction chamber in a cartridge. In one embodiment, a series of bead chambers with different lyophilized reagents may be provided such that sample fluid can sequentially pass through them. In another embodiment, bead chambers may be located on a movable carrier, for example a rotating carousel, from which they may selectively be connected to a reaction chamber in a cartridge. In still another embodiment, the bead chamber () may comprise at least one flexible wall (FW) allowing for a minimization of dead volume associated with the extraction of lyophilized reagent (LB).

Fluidic system for processing a sample fluid

A method of aligning a template and a substrate for imprint lithography involves using a mask pattern of the template and a luminescent marker pattern of the substrate, the method including aligning the template mask pattern and the substrate marker pattern using a radiation intensity measurement of radiation emitted by the luminescent marker pattern and having passed the template mask pattern. The mask pattern and the luminescent marker pattern may each be shaped to provide a turning point in the intensity of detected radiation emitted from the marker pattern, and passing through the mask pattern to a detector, as a function of relative displacement at the aligned position. The displacement of the template and substrate may be aligned by identifying the turning point in radiation intensity. The marker pattern may be fluorescent with the emitted radiation excited by a radiation source.

Imprint lithography alignment method and apparatus

A medicament delivery device, which comprises a driving mechanism and a housing () having a reservoir (), which is at least partly filled with a substance and which is sealed at least on one side with a flexible wall (). The driving mechanism is adapted to press a piston () against the flexible wall () thereby releasing the substance from the reservoir () through an opening () in the reservoir (). This provides for a safe and reliable medicament delivery device.

Medicament delivery device, capsule and in vivo medicine delivery or diagnostic system

An ingestible capsule () is provided for delivery of a drug, the capsule () comprises a first module () and a second module (). The first module () has at least one drug compartment () for comprising an amount of the drug. The drug compartment () is sealed by a foil () with an embedded conducting heating wire (). The second () module comprises electronics () for providing an electrical pulse to the heating wire () in order to open the drug compartment () by melting the foil (). The first module () and second module () comprise interoperable connection means () for securing the first module () to the second module () such that the heating wire () is electronically coupled to the electronics ().

Modular ingestible drug delivery capsule

The present invention relates to a method for producing a storable dry composition of biomolecule. First a composition is dispensed on a surface. The composition comprises at least a biomolecule, at least a liquid volatile component, at least a polysaccharide being designed for forming together with the at least a biomolecule and a part of the at least a liquid volatile component a matrix displaying a glass transition temperature Tg. Secondly, at least a part of the liquid volatile component is evaporated by adjusting the temperature of said composition to allow the formation of the matrix. Said evaporation step is initiated at an initial temperature T, and finished up at a final temperature T, said final temperature Tbeing above said initial temperature T

Biomolecule drying process for long-term storage

The present invention relates to a method for immobilizing nucleic acids on a support, comprising the provision of a nucleic acid with a stretch of nucleotides of only one basetype and the immobilization of said nucleic acid on a support by crosslinking by light, wherein said crosslinking by light is performed at a wavelength of about 300-500 nm, preferably at a wavelength of 365 nm. The present invention further relates to a method for the analysis of nucleic acids immobilized according to the invention, which comprises the hybridization of the immobilized nucleic acid with complementary and mismatch segments. Furthermore, the present invention relates to immobilized nucleic acids obtainable by the method of the invention, the use of accordingly immobilized nucleic acids for the production of nucleic acid arrays and a diagnostic kit, comprising an array of nucleic acids which are immobilized according to the present invention.

Method for immobilizing nucleic acids on a support

An inkjet device for controlled positioning of a droplet of a substance onto a substrate includes a print head having a nozzle configured to eject the droplet. A camera is configured to detect and generate images of the droplet after ejection of the droplet from the nozzle. If the droplet volume, velocity, flight path, viscosity or surface tension start to deviate from preset values, a computer is configured to correct for this in a closed loop manner. If the droplet fails to eject, the computer is configured to stop the inkjet device and an operator can maintain the print head. The computer is configured to determine viscosity and surface tension of the droplet from characteristics of the droplet identified from the droplet images, and the computer is configured to control the positioning of the droplet onto the substrate during the printing process based on the determined viscosity and surface tension.

Inkjet device and method for the controlled positioning of droplets of a substance onto a substrate

An electronic capsule () is provided. The capsule () has a discrete drive element () comprising: a housing (), electronics for making the electronic capsule () operable, a pumping mechanism () for dosing and displacing a substance, a power source () for powering the electronic capsule () and enabling the electronics and the pumping mechanism () to operate, and a locking mechanism (); and a discrete payload element () comprising: a housing (), a reservoir () for storing the substance, one or more openings () in the housing () for releasing the substance from the reservoir () and a locking mechanism () for engaging the drive element locking mechanism (). Engagement of the drive element locking mechanism () with the payload element locking mechanism () secures the drive element () to the payload element (), thereby making the electronic capsule () operable and specific.

Medicament delivery apparatus

Growing community of inventors

Eindhoven, Netherlands

Anke Pierik