Hologic, Inc.

Medispectra, Incorporated

Cytyc Corporation

Thrive Earlier Detection Corp.

Intelligent Medical Devices, Inc.

Howard B Kaufman

Anthony P Shuber

Alex R Zelenchuk

Ross Flewelling

Erin Coffman

Paul MacLean

Steven Hecht

Philippe Schmid

Leonardo Hagmann

Isaac A Kinde

David J Zahniser

Kevin Schomacker

Tuan Thuc Ha

Barry F Hunt

Kam Lin Wong

James R Linder

Robert Nordstrom

Peter J Costa

Kwong Hui

Kathy K Mui

Ze'ev Hed

Eileen Ludlow

Tuan Ha

Paul Maclean

Kathy Mui

High throughput personal genomic testing has created a need for robust quality control mechanisms to track sample identity, reagent integrity, and other factors with significant influence on assay performance. A method of massively parallel sequencing using an accompanying barcoded molecular standard enables one to track nucleic acid analytes to identify them by project, lot, batch, or patient. The molecular standard contains sequences present in the analyte, allowing it to be processed simultaneously without any other additional reagents. Within the molecular standard, a calibrator sequence permits assessment of fidelity of sequence determination. Additional sequences in the molecular standard may be used to manipulate the molecular standard separate from the analyte. The molecular standard can be used to benchmark sequencing platforms and assess error rates.

Barcoded molecular standards

The present disclosure describes a method of treating a sample comprising cells with a process of partial lysing. Cells are exposed to a process such as bead beating that lyses some cells in the mixture. The process generates a resultant sample mixture that is suitable for both cell morphology screening and genetic screening.

Method of partial lysis and assay

The present disclosure describes a method of treating a sample comprising cells with a process of partial lysing. Cells are exposed to a process such as bead beating that lyses some cells in the mixture. The process generates a resultant sample mixture that is suitable for both cell morphology screening and genetic screening. A first portion of the partially lysed sample can be mounted on a slide and observed for atypical cells and cytologic abnormalities. A second portion of the partially lysed sample can be screened for genetic markers known to correlate with a risk of cervical cancer. The method is particularly useful for cervical screening, where a combination of cytology and genetic screening present a more complete picture of cervical health. The disclosed method streamlines the diagnostic process for protocols that require both types of assays, without compromising screening accuracy.

Systems and methods of use to facilitate classification of cytological specimens are discussed. The system acquires or imports image data of a cytological specimen. The imported image data may include, or the system may otherwise perform an image analysis to identify one or more objects of interest in a respective specimen image dataset, including feature attributes for the identified objects. The system analyzes the feature attributes by predetermined criteria and/or optionally with user inputted criteria. The system includes an analysis tool that assists the user in identifying cytologically abnormal objects, if present in a particular specimen, by manipulating and viewing images of objects selected as a function of feature attributes. More generally, the analysis tool aides the user to find, extract, and display abnormal objects from within a large dataset of images and facilitates navigation through large amounts of image data and enables the efficient classification of the entire specimen.

System and method for reviewing and analyzing cytological specimens

A computer-assisted method of classifying cytological samples, includes using a processor to analyze images of cytological samples and identify cytological objects of interest within the sample images, wherein the processor (i) displays images of identified cytological objects of interest from the sample images to a reviewer, (ii) accesses a database of images of previously classified cytological objects, and (iii) displays to the reviewer, interspersed with the displayed images of the identified objects of interest from the sample images, one or more images obtained from the database of images of previously-classified objects.

Method for automatically seeding previously-classified images among images of objects of interest from a specimen

Methods and systems for collecting cells on a filter disposed in a specimen fluid containing suspended cells of a biological specimen. A short vacuum pulse is applied across a filter to sip specimen fluid. A percentage or portion of the filter surface area covered by cells is determined is representative of or correlates to the density of cells in the specimen fluid. A maximum vacuum amplitude and/or duration are determined utilizing the determined filter coverage. A longer, continuous vacuum or slurp is applied across the filter to collect cells on the filter while limiting the amplitude and/or duration of the slurp based at least in part upon the determined maximum vacuum amplitude and/or duration.

Methods and systems for collecting cells of a biological specimen

An apparatus for processing a specimen from a fluid sample includes a first set of one or more microfluidic channels configured to deliver the sample fluid to a filter disposed on an inflatable bladder configured to transfer the specimen from the filter to a slide. The apparatus is configured to collect an approximate monolayer of particles and includes a second set of one or more microfluidic channels configured to remove fluid flowing through the filter disposed on the inflatable bladder. The apparatus also includes a pressure source, a sample container connected to the pressure source and the first set of one or more microfluidic channels, a fluid flow gauge configured to measure a fluid flow rate through the filter, and a stain source connected to the first set of one or more microfluidic channels.

Microfluidic apparatus and method for preparing cytological specimens

A handheld apparatus for preparing a specimen slide includes a handle, a filter holder assembly coupled to and extending from the handle; and a slide holder assembly coupled to and extending from the handle spaced apart from the filter holder assembly, wherein the slide holder assembly comprises a plurality of positioning members movably coupled to one another, and a slide holder movably coupled to one of the positioning members to allow a slide mounted on the slide holder to make rolling contact with an outward facing surface of a filter mounted on the filter holder assembly.

Apparatus for preparing cytological specimens

Methods, systems and computer readable media for processing one or more biological specimens carried by specimen slides. Images of objects in a specimen are acquired and objects of interest in the acquired images are identified. Additional images of identified objects of interest may be acquired at multiple wavelengths. Cellular features of objects of interest are extracted from images and may be used for classifying the specimen, e.g., as normal or suspicious/abnormal, based a probabilistic model that utilizes the extracted features.

Methods and systems for processing biological specimens utilizing multiple wavelengths

The invention provides methods of relating a plurality of images based on measures of similarity. The methods of the invention are useful in the segmentation of a sequence of colposcopic images of tissue, for example. The methods may be applied in the determination of tissue characteristics in acetowhitening testing of cervical tissue, for example.

Image processing using measures of similarity

A system and method for determining an in vivo property of a tissue or blood is described. The in vivo property may be a hematocrit value, a hemoglobin concentration, or a combination thereof. The system can automatically determine a location of a subcutaneous blood vessel. Based on the automatically determined location, the system illuminates the blood vessel with a light beam and detects light resulting from the illumination. The system determines the in vivo property based on the detected light. Alternatively, or in combination, the system displays an image corresponding to a spatial relationship between a subcutaneous blood vessel and a light beam. Based on the image, an operator can adjust the light beam with respect to the blood vessel to have a selected spatial relationship. The system determines an in vivo property based on the illumination of the blood vessel when the light beam has the selected spatial relationship.

Optical determination of in vivo properties

The invention provides methods for determining a characteristic of a tissue sample, such as a state of health, using spectral data and/or images obtained within an optimal period of time following the application of a chemical agent to the tissue sample. The invention provides methods of determining such optimal windows of time. Similarly, the invention provides methods of determining other criteria for triggering the acquisition of an optical signal for classifying the state of health of a region of a tissue sample.

Optimal windows for obtaining optical data for characterization of tissue samples

The invention provides methods and systems for monitoring effects of chemical agents on optical signals produced by samples in response to the chemical agents. Preferred methods comprise application of multiple chemical agents that interact to alter an optical signal from the sample. Methods and systems of the invention also comprise monitoring an optical signal from an endogenous chromophore upon application of a chemical agent to a sample. Methods and systems of the invention also comprise the use of triggers, atomizers and image alignment to enhance the results of methods described herein.

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Newton, MA, United States of America

Howard B Kaufman