International Business Machines Corporation

Bio-rad Laboratories, Inc.

Technion Research & Development Foundation Limited

Bio-rad Europe Gmbh

Govind V Kaigala

Robert Dean Lovchik

Emmanuel Delamarche

Xander Frank Van Kooten

David P Taylor

Anna Fomitcheva Khartchenko

Moran Bercovici

Aditya Kashyap

Julien Autebert

Federico Paratore

Iago Pereiro Pereiro

Nadya Ostromohov

Maria Gabrani

Martina Hitzbleck

Pushpak Pati

Ismael Zeaf

Lorenzo Franco Teodoro Petrini

Gustavo Alejandro Stolovitzky

Jaione Tirapu Azpiroz

Yuksel Temiz

Itay Barak

Onur Gökçe

Yochanan Uri

Seyed Ali Kazemi Oskooei

Laurent Guillon

Tobias Guenzler

Tino Treiber

Nuri Murat Arar

Navneet Dogra

Daniel Widerker

Emilie Frisan

Lena Voith Von Voithenberg

Xander Van Kooten

Claudia I Trainito

Marcel Buerge

Robert Vogel

Julien Cors

Patterning a substrate can be provided. A substrate is covered by an immersion liquid and a microfluidic probe head is positioned in proximity with the surface of the substrate, so as to immerse a processing surface of the probe head in the immersion liquid. Liquid flows are generated between the processing surface of the probe head and the surface of the substrate, via the probe head. The liquid flows generated include an etching flow of an etching liquid (e.g., an acid or solvent) and a processing flow of a processing liquid (e.g., a solution or suspension).

Subtractive microfabrication and functionalization of substrates by hydrodynamic flow confinements

The present disclosure is notably directed to a microfluidic probe head (), or MFP head, comprising a processing surface () having liquid injection and liquid aspiration apertures, as well as projections () extending from the processing surface (). The arrangement of injection and aspiration apertures provides for a hydrodynamic flow confinement within a processing region that is formed between the processing surface () and a substrate () or sample surface (for example, the bottom of a microtiter plate sample well ()), typically located beneath the processing surface (). The disclosure is further directed to related microfluidic probe devices, and methods of operation of such an MFP head, notably to deposit cells on a surface.

Microfluidic probe head with aspiration posts

A microfluidic device may be provided. The microfluidic device comprises a processing surface having an aperture. The microfluidic device comprises a liquid ejection channel. The liquid ejection channel guides to the aperture. The microfluidic device comprises a first liquid injection channel guiding to the liquid ejection channel. The first liquid injection channel has a first end and a second end and is arranged to provide a fluid flow from the first end to the second end. At least a portion of the first liquid injection channel is closer to the processing surface than (both) the first and second ends to sediment particles.

Structures on microfluidic devices to control sedimentation

The present disclosure is notably directed to a microfluidic probe head, or MFP head, comprising a processing surface having a liquid injection aperture and a liquid aspiration aperture thereon. The aspiration aperture is generally shaped so as to partly extend around the injection aperture on the processing surface, although such injection apertures are not completely surrounded by the slit on the processing surface. Further, fluidic and solid barriers to aspiration are considered. The disclosure is further directed to related microfluidic probe devices, and methods of operation of such an MFP head, notably to deposit cells on a surface.

Microfluidic probe head with barrier projections

A microtiter plate comprising a first array of M×N wells and a microfluidic probe insert is provided. The microfluidic probe insert includes a second array of M×N microfluidic probe conduits, forming N columns of M conduits. The M conduits include respective orifices in a bounding plane and extend, each, perpendicularly to the bounding plane on one side. The microfluidic probe insert also includes N vacuum circuits, each comprising at least one vacuum port and M openings in the bounding plane, where 2≤M, 2≤N. The microfluidic probe insert is positioned on the microtiter plate and the microfluidic probe conduits are inserted in respective wells. A processing liquid is ejected from M conduits via the M orifices of the M conduits by applying a negative pressure to a corresponding set of N vacuum circuits via the respective one or more vacuum ports.

Multiplexed microfluidic probe insert for microtiter plates

Embodiments of the invention relate to a computer-implemented method for quantifying a biomarker in a tissue sample of an organism. An image analysis system receives images of a stained tissue sample. Each received digital image depicts the tissue sample region at the end of an exposure interval. The system analyzes the intensity values and exposure intervals of the received digital images for determining the time when the intensity values corresponding to the plurality of exposure intervals ordered according to ascending exposure interval lengths reach a plateau (saturation residence time&#x2014;SRT). The system determines the amount of a biomarker in the tissue sample and/or predicts a tumor stage and/or a treatment recommendation as a function of the SRT.

Biomarker quantification in a tissue sample

A microfluidic probe head is provided. The microfluidic probe head comprises a processing surface. The processing surface has a first and second aperture and a fluid injection channel, which leads to the first aperture. The microfluidic probe head comprises also a first fluid aspiration channel which leads to the second aperture. Thereby, the second aperture forms a slot in the processing surface. Furthermore, a microfluidic probe may be provided comprising the microfluidic probe head.

Structures to define flow confinement shape and confinement stability with uniform aspiration

Techniques regarding measuring a position and transcriptome of one or more cells from a biological sample are provided. For example, one or more embodiments described herein can comprise a method, which can comprise covalently bonding a probe to a molecular structure located on a cell to label the cell according to a position of the cell with regards to a biological sample comprising the cell. The probe comprises an oligonucleotide sequence that can be indicative of the position.

Determining position and transcriptomes of biological cells

A microfluidic probe includes a probe head with a processing surface that includes a first aperture and a second aperture. The probe further includes a liquid injection channel, which leads to the first aperture, and a liquid aspiration channel, which extends from the second aperture. The probe also includes a bypass channel, arranged so as to fluidly connect the liquid injection channel to the liquid aspiration channel, as well as a control channel. The latter fluidly connects to the bypass channel, hence forming a junction therewith, so as to define two portions of the bypass channel. These portions includes: a first portion that extends from the junction to the liquid injection channel; and a second portion that extends from that same junction to the liquid aspiration channel. The invention is further directed to methods of operation of a probe as described above, to process a surface.

Microfluidic probe with bypass and control channels

A method for manufacturing a fluidic device is provided. The method comprises providing a capillary, providing a structure having a fluidic channel and an opening, reducing an outer diameter of a portion of the capillary to be smaller than the opening of the structure. Furthermore, the method comprises inserting, at least partly, the portion of the capillary through the opening of the structure into the fluidic channel and applying heat to the structure to expand the inserted portion of the capillary to fit the capillary to the structure.

Prevention and bubble removal from microfluidic devices

The present invention provides, in some embodiments, an isotachophoresis (ITP) apparatus, a kit comprising same and method of use thereof for the focusing analytes of interest from large sample volumes.

Device and method for isotachophoretic focusing large sample volumes

Embodiments of the invention are directed to a method of separating and encapsulating an analyte on a microfluidic device in order to extract the analyte. A microfluidic device is provided having a main microchannel and a set of one or more auxiliary microchannels, each branching to the main microchannel at respective junctions therewith. A mixture is introduced as a single phase in the main microchannel in order to electrokinetically separate an analyte from the introduced mixture, and in order to confine the separated analyte in a microchannel portion of the main microchannel. The microchannel portion adjoins one of the junctions. One or more encapsulating volumes of an encapsulating phase are injected in the main microchannel via one or more of the auxiliary microchannels. The encapsulating phase is immiscible with said single phase. The encapsulated analyte is extracted from the main microchannel via one or more of the auxiliary microchannels.

Electrokinetically separating, encapsulating and extracting analytes on a microfluidic device

Microfluidic probe head for processing a sequence of separate liquid volumes separated by spacers. The microfluidic probe head includes: an inlet, an outlet, a first fluid channel and a second fluid channel and a fluid bypass connecting the first fluid channel and the second fluid channel. The first fluid channel delivers the sequence of separate liquid volumes from the inlet toward a deposition area, the fluid bypass allows the spacers to be removed from the first fluid channel obtaining a free sequence of separate liquid volumes without spacers, the first fluid channel delivers the free sequence of separate liquid volumes to the deposition area, and the second fluid channel delivers the removed spacers from the fluid bypass to the outlet. The present invention also provides a microfluidic probe and method for processing a sequence of separate liquid volumes.

Microfluidic probe head for processing a sequence of liquid volumes separated by spacers

An apparatus for a vacuum-driven microfluidic probe includes a body with an apex and a processing surface, at an end of the body. The apparatus also includes a partially open cavity formed as a recess on the processing surface and a set of apertures in the cavity, where the set of apertures include a sample outlet aperture intersected by a vertical axis of the cavity. The apparatus also includes aspiration apertures radially distributed around said vertical axis, wherein the apex is further configured to generate a pressure in the cavity upon aspirating an external liquid through the aspiration apertures that causes to aspirate a liquid sample from the sample outlet aperture, so as to eject the aspirated liquid sample from the probe.

Vacuum-driven microfluidic probes

One or more embodiments of the present invention are directed to a method for processing a surface with a vertical microfluidic probe head. The method includes positioning the microfluidic probe head so as for the edge surface to face a surface to be processed. Next, the method dispenses processing liquid via each orifice of the first one of the sets of n orifices, so as for the dispensed processing liquid to process the surface; and aspirates liquid via each orifice of the second one of the sets of n orifices.

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Rüschlikon, Switzerland

Govind V Kaigala