Ventana Medical Systems, Inc.

Ventana Medic Systems, Inc.

Roche Diagnostics Gmbh

F. Hoffmann-la Roche Ag

Daniel Bauer

Michael Otter

David Chafin

Benjamin C Stevens

Niels Kroeger-Lui

Abbey Theiss

Nazim Shaikh

The subject disclosure presents systems and computer-implemented methods for evaluating a tissue sample that has been removed from a subject. A change in speed of the energy traveling through the sample is evaluated to monitor changes in the biological sample during processing. The rate of change in the speed of the energy is correlated with the extent of diffusion. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. A time-of-flight of acoustic waves and rate of change thereof is monitored to determine an optimal time for soaking the tissue sample in a fixative.

Diffusion monitoring protocol for optimized tissue fixation

A method and system for classifying field of view (FOV) images of histological slides into various categories that include certain stain patterns, artifacts, and/or other features of interest are provided herein. Few-shot learning (e.g., a prototypical network) techniques are used to train a deep convolutional neural network using a small number of training samples for a small number of image classes for classifying stain images belonging to a larger number of image classes.

Histological stain pattern and artifacts classification using few-shot learning

Disclosed are a system and method for evaluating a tissue sample that has been removed from a subject. Movement of fluid through the tissue sample is monitored by measuring time of flight of acoustic waves passed through the tissue sample. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. Using the disclosed method and system, an optimized protocol for ensuring adequate distribution of the fluid throughout a variety of tissue types and/or sample sizes can be developed and utilized.

Standardizing diffusion of a fluid into tissue

A method is disclosed that permits calculation of reagent concentrations (in SI units) over time and space within a tissue sample as the sample is immersed in the reagent and the reagent diffuses into the tissue sample. The disclosed method has yielded the surprising result that once a formaldehyde concentration at all points within a tissue sample exceeds about 90 mM during a cold step of a cold+hot fixation protocol, the hot step of the fixation protocol can be commenced to provide reliable detection of molecular targets and preservation of tissue morphology in downstream analyses.

System and method for sample preservation

A method and system are described for processing tissues according to particular processing protocols that are established based on time-of-flight measurements as a processing fluid is diffused into a tissue sample. In one embodiment, measurement of the time it takes about 70% ethanol to diffuse into a tissue sample is used to predict the time it will take to diffuse other processing fluids into the same or similar tissue samples. Advantageously, the disclosed method and system can reduce overall processing times and help ensure that only samples that require similar processing conditions are batched together.

System and method for sample processing

The subject disclosure presents systems and computer-implemented methods for determining an acoustic time-of-flight (TOF) of sound waves through a sample material with greater accuracy and in a more repeatable fashion, by invoking one or more of an envelope generation for an error function, fitting a non-linear curve to an ultrasound frequency sweep, or performing a clustered piece-wise linear regression on individual linear parts of the ultrasonic frequency sweep. The systems and methods are useful for, among other things, monitoring diffusion of fluids through porous materials, such as tissue samples.

Accurately calculating acoustic time-of-flight

The subject disclosure presents systems and computer-implemented methods for calculating the diffusivity constant of a sample using acoustic time-of-flight (TOF) based information correlated with a diffusion model to reconstruct a sample's diffusivity coefficient. Operations disclosed herein such as acoustically determining the phase differential accumulated through passive fluid exchange (i.e. diffusion) based on the geometry of the tissue sample, modeling the impact of the diffusion on the TOF, and using a post-processing algorithm to correlate the results to determine the diffusivity constant, are enabled by monitoring the changes in the speed of sound caused by penetration of fixative such as formalin into several tissue samples. A tissue preparation system may be adapted to monitor said diffusion of a tissue sample and determine an optimal processing workflow.

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Tucson, AZ, United States of America

Daniel Bauer