A method of automated measurement of motility and morphology parameters of the same single motile sperm. Automated motility and morphology measurements of the same single sperm are performed under different microscope magnifications. The same single motile sperm is automatically positioned and kept inside microscope field of view and in focus after magnification switch. A method of automated non-invasive measurement of sperm morphology parameters under high magnification of imaging. Sperm morphology parameters including subcellular structures are automatically measured without invasive sample staining. A method of automatically selecting sperms with normal motility and morphology and DNA integrity for infertility treatment.
Drawings
Claims20
A computer implemented method of automatically quantifying motility and morphology parameters of a single motile microscopic specimen in a population of motile specimens using a computer, characterized in that said method comprises the following steps:
(a) placing, or enabling the placement of, the population of motile microscopic specimens on a stage of a microscope means, the microscope means having (i) a motorized positioner controlling the motion of the stage, (ii) a motorized objective nosepiece, (iii) a first microscope magnification objective and a second magnification objective mounted on the motorized objective nosepiece, the second magnification objective having a higher magnification power than the first magnification objective, (iv) an image acquiring unit mounted on the microscope means, and (v) a focus adjusting motor, the motorized positioner, motorized objective nosepiece, the image acquiring unit and the focus adjusting motor being operationally connected to the computer;
(b) automatically obtaining images of the population of motile microscopic specimens using the image acquiring unit through the first microscope magnification objective;
(c) automatically moving the motorized positioner for tracking a plurality of motile microscopic specimens in the population based on the images taken through the first microscope magnification objective to quantify the motility parameters of the tracked motile microscopic specimens;
(d) selecting a single motile microscopic specimen using the quantified motility parameters;
(e) automatically (i) switching to a second magnification objective using the motorized nosepiece, (ii) positioning said selected single motile microscopic specimen inside a field of view of said second magnification objective using the motorized positioner, (iii) re-focusing on the single motile microscopic specimen using the focus adjusting motor, and (iv) obtaining images with the image acquiring unit of the single motile microscopic specimen through the second magnification objective;
and
(f) quantitatively measuring morphology parameters of said selected single motile microscopic specimen using the microscopic images taken with the second magnification objective.
4 more elements
A method for automated non-invasive measurement of a morphological feature or features of a live, unstained motile microscopic specimen, comprising:
(a) automatically segmenting the morphological feature or features of the motile microscopic specimen under a microscope, and
(b) automatically measuring the morphological feature or features under the microscope wherein (i) step (a) comprises automatically segmenting at least two morphological features of the motile microscopic specimen;
(ii) the morphological feature is the sperm's midpiece, and abnormalities in midpiece size and midpiece angle are measured by a minimum bounding box or a convex hull;
(iii) the morphological feature is the sperm's midpiece, and an excess residual cytoplasm on the midpiece is detected by inspecting abnormal width of the midpiece;
or
(iv) the morphological feature is the tail, and (a) an abnormality in tail coiling is automatically detected by detecting closed contours on the sperm tail;
(b) an abnormality in tail bending is automatically detected by detecting a sharp turn in a centerline of the sperm tail;
and
(c) an abnormality of tail width non-uniformity is automatically detected by measuring a distribution of a distance from points along the tail's contour to a centerline of the sperm tail;
21 May 2039Estimated · howhide20 years from earliest known nonprovisional domestic filing plus recorded patent term adjustment. Maintenance-fee lapses, terminal disclaimers and statutory extensions have not been checked. The continuity chain may be incomplete; this is not an enforceability determination.
Optical investigation techniques, e.g. flow cytometry: signal processing
Life of this patent
About 12 years 7 months of term left · ends 21 May 2039 (estimated)
Priority, United Kingdom21 May 2018
Filed21 May 2019
Published2 Sep 2021
Granted27 Dec 2022
Today12 Oct 2026
Term ends21 May 2039
Priority, United Kingdom21 May 2018
Granted27 Dec 2022
Term ends21 May 2039
Priority claimedGB 1808312
Application filedUS 17/057,504
PublishedUS 2021/0270717 A1
Assigned to The Governing Council of the University of Torontoassignment of assignor's interest
GrantedUS 11,536,643 B2
Assigned to Toronto Nano Instrumentation Inc.assignment of assignor's interest
Assigned to Suzhou Boundless Medical Technology Co., Ltd.assignment of assignor's interest
TodayWithin its term
Term endsEstimated
Description10,166 words
Summary3,557 words
#This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/CA2019/050690 filed 21 May 2019 entitled “A method for automated non-invasive measurement of sperm motility and morphology and automated selection of a sperm with high DNA integrity,” which claims priority to United Kingdom Patent Application No. 1808312.1 filed 21 May 2018, and the contents of each are hereby incorporated herein in their entirety by reference for all purposes.
#The invention relates to methods for automated motility and morphology measurement of the same single motile sperm under different microscope magnifications and automated selection of sperms with normal motility and morphology.
#The World Health Organization (WHO) reports that 48.5 million couples worldwide experience infertility, and many of these couples seek in vitro fertilization (IVF) for treatments. There are presently approximately 3,000 IVF clinics worldwide, with 458 clinics in the U.S. alone, and the number is growing rapidly. Measurement of sperm motility and morphology is important for IVF, with wide applications such as male infertility diagnosis and selecting the sperm for IVF treatment such as intracytoplasmic sperm injection (ICSI).
Brief description of the drawings12 figures
#A detailed description of one or more embodiments is provided herein below by way of example only and with reference to the following drawings, in which:
#FIG. 1 illustrates a schematic view of the system for automatically quantifying motility and morphology parameters of the same single motile sperm in accordance to one embodiment of the present invention.
#FIG. 2 illustrates an operation sequence of the method for automatically quantifying motility and morphology parameters of the same single motile sperm in accordance to one embodiment of the present invention.
Detailed description6,221 words
#The following definitions, unless otherwise stated, apply to all aspects and embodiments of the present application. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Also, unless indicated otherwise, except within the claims, the use of “or” includes “and” and vice versa. Non-limiting terms are not to be construed as limiting unless expressly stated or the context clearly indicates otherwise (for example “including”, “having” and “comprising” typically indicate “include without limitation”). Singular forms included in the claims such as “a”, “an” and “the” include the plural reference unless expressly stated otherwise. All relevant reference, including patents, patent applications, government publications, government regulations, and academic literature are hereinafter detailed and incorporated by reference in their entireties.
#The terms “population” or “plurality,” as used herein, is defined as two or more than two. The term “another,” as used herein, is defined as at least a second or more. The phrase “at least one of . . . and . . . ” as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. As an example, the phrase “at least one of A, B and C” includes A only, B only, C only, or any combination thereof (e.g. AB, AC, BC or ABC). The term “substantially” includes exactly the term it modifies and slight variations therefrom.
#The term “about” modifying any amount refers to the variation in that amount encountered in real world conditions of producing materials such as polymers or composite materials, e.g., in the lab, pilot plant, or production facility. For example, an amount of an ingredient employed in a mixture when modified by about includes the variation and degree of care typically employed in measuring in a plant or lab and the variation inherent in the analytical method. Whether or not modified by about, the amounts include equivalents to those amounts. Any quantity stated herein and modified by “about” can also be employed in the present invention as the amount not modified by about.