News Column

"Diagnostic Apparatus" in Patent Application Approval Process

September 10, 2014



By a News Reporter-Staff News Editor at Electronics Newsweekly -- A patent application by the inventors Bresolin, Stefano (Garner, NC); Calderwood, David A. (Chapel Hill, NC); Heineck, Tobias M. (Durham, NC); Newcomb, David (Morrisville, NC); Paul, Chris (Hillsborough, NC); Pollard, Jasper N. (Durham, NC); Rodriguez, Rodolfo R. (Cary, NC); Young, Demetris (Durham, NC), filed on July 2, 2013, was made available online on August 28, 2014, according to news reporting originating from Washington, D.C., by VerticalNews correspondents.

This patent application has not been assigned to a company or institution.

The following quote was obtained by the news editors from the background information supplied by the inventors: "Mastitis is the inflammation of the mammary gland caused by microorganisms that invade one or more quadrants of the bovine udder, multiply, and produce toxins that are harmful to the mammary gland. Economic loss to mastitis in the United States is estimated to be over 2 billion dollars. This is approximately 10% of the total value of farm milk sales, and about two-thirds of this loss is due to reduced milk production in subclinically infected cows.

"In subclinical mastitis, there may be no visible signs of the disease, and diagnosis of subclinical mastitis may be performed by a somatic cell count (SCC) of the milk. The SCC is the number of leukocytes or white blood cells per volume of milk and is also used as an index of milk quality. It has also been recognized that there are multiple types of leukocytes, each with its own significance. In milk from a healthy animal, the predominant cell types are lymphocytes, followed by much lesser numbers of neutrophils and macrophages. The percentages of each kind of cell rise and fall as part of the immune response to infection. Those percentages, 'the differential milk leukocyte count', represent the unique immune status of an individual quarter udder, at a specific point in time for better diagnosis of subclinical mastitis.

"One method for detecting the differential milk leukocyte count is using flow-cytometry, which is an expensive, sophisticated tool typically only found in top research laboratories and generally not practical for the farmer. Another method for detecting the differential milk leukocyte count is the 'manual milk differential smear' (MMDS), which is a difficult and time consuming procedure, and is subject to great variability, even when performed by highly trained laboratory technologists. Both flow-cytometry and MMDS present practical difficulties for field research or a barn environment.

"U.S. Patent Application Publication No. 2009/0233329 to Rodriguez discloses a wedge microfluidic slide chamber for detecting mastitis or other diseases from a body fluid of a mammal, such as from cow's milk. While manual and automated procedures for carrying out disease detection with the aid of such a sample cartridge are described, again there is not described a system and apparatus useful for implementing such procedures in a field or barn environment."

In addition to the background information obtained for this patent application, VerticalNews journalists also obtained the inventors' summary information for this patent application: "A first aspect of the invention is an automated microscope apparatus, comprising: an outer housing having an external wall; optionally but preferably an internal wall in said housing, and configured to form a first compartment and a separate second compartment in said outer housing; a microscope assembly in said housing, preferably in said first compartment; and a microprocessor in said housing, preferably in said second compartment; and optionally but preferably a heat sink mounted on said housing external wall, preferably adjacent said second compartment, with said microprocessor thermally coupled to said heat sink and operatively associated with said microscope assembly.

"In some embodiments, the microscope assembly comprises: a support frame; a subframe; a plurality of vibration isolators connecting said support frame to said subframe; an XYZ stage connected to said subframe; and an optical stage connected to said subframe. An XYZ drive assembly interconnecting said XYZ stage to said subframe is preferably included.

"In some embodiments, the microprocessor is included as a passively cooled microprocessor assembly, comprising: a heat sink having a front surface and back surface; a circuit board having a front surface and back surface, with said microprocessor mounted on said circuit board front surface; a thermal coupler positioned between said microprocessor and said heat sink back surface, said thermal coupler fixed to and in thermal contact with said heat sink back surface; a clamp connected to said thermal coupler and configured to clamp said microprocessor to said thermal coupler, thereby placing said microprocessor, said thermal coupler, and said heat sink in thermal contact with one another.

"In some embodiments, the XYZ stage is for securing a sample cartridge in the automated microscope having X, Y, and Z planes of movement, the sample cartridge having an end portion, a pair of generally parallel opposing side edge portions, and a locking edge portion formed thereon. The XYZ stage comprises a base member having a planar stage surface portion; a pair of generally parallel oppositely facing guide members on said planar stage surface and configured for slideably receiving said cartridge therebetween; and a locking member on said planar stage surface portion and positioned to press against the sample cartridge locking edge portion when said sample cartridge is inserted between said guide members, so that pressure is exerted by said lock member through said sample cartridge against at least one of said guide members, whereby the cartridge is removably locked in place on the XYZ stage in the Z plane.

"A further aspect of the invention is an automated system for detecting a disorder in a subject, comprising: an XYZ stage configured to secure a sample cartridge; said sample cartridge comprising at least one chamber, said at least one chamber containing a biological sample collected from a subject; an imaging system operatively associated with said XYZ stage and configured to image selected cells in said sample, said selected cells including at least neutrophils; an autofocusing system operatively associated with said imaging system and said XYZ stage and configured to focus said imaging system on said at least one chamber; a processor running a software program or other suitable means for generating a count of at least neutrophils in said sample as an aid to detecting a disorder in said subject. In some embodiments, where the cartridge contains multiple chambers, the system may include a controller configured to optionally repeat at least said imaging for at least one additional chamber on said cartridge, as discussed further below.

"A further aspect of the invention is a method of automatically focusing a microscope on a specimen by capturing an image from each of a plurality of focal planes in or on said specimen, calculating a focus score for each of said images, selecting the focal plane corresponding to the image having the best focus score, and then repositioning said specimen relative to said microscope so that said microscope is focused on said selected focal plane, characterized by including a plurality of exogenous targets in or on said specimen.

"A further aspect of the invention is an automated microscope comprising a specimen support stage, an objective lens, a camera, at least one drive assembly operatively associated with said support stage and/or said objective lens, all of which may be as described herein, and further characterized by a controller operatively associated with said at least one drive assembly for carrying out an autofocus method as described herein.

"The foregoing and other objects and aspects of the present invention are described in greater detail below. The disclosures of all US Patent references cited herein are to be incorporated herein by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

"FIG. 1 is a partial schematic diagram of an apparatus of the present invention.

"FIG. 2 is a perspective view of an apparatus of the present invention, with a sample cartridge to be inserted and touch screen user interface for input of information and display of results.

"FIG. 3 is a schematic diagram of an apparatus of the present invention, showing vibration damping components and chamber separation.

"FIG. 4 is a cut-away perspective view of the apparatus of FIG. 2.

"FIG. 5 is a side sectional view of an optical stage of the apparatus of FIG. 2, showing the light source, objective lens, filters, dichroic mirror and camera.

"FIG. 6 is a perspective view of a microscope assembly and passively cooled microprocessor assembly of the apparatus of FIG. 2 with the cover removed and support frames removed.

"FIG. 7 is a perspective view of a microscope assembly of the apparatus of FIG. 2, with the support frame removed, showing the XYZ drive.

"FIG. 8 is a perspective view of the mount, vibration dampers, and support frame of a microscope assembly of FIG. 2, upon which the optical stage of FIG. 5 is to be mounted.

"FIG. 9 is a perspective view of a passively cooled microprocessor assembly of the apparatus of FIG. 2.

"FIG. 10 is an exploded view of the microprocessor assembly of FIG. 9.

"FIG. 11 is a perspective view of an XYZ stage of the apparatus of FIG. 2, as configured for retaining a pair of sample cartridges.

"FIG. 12 is a top plan view of the XYZ stage of FIG. 11.

"FIG. 13 is a side view of the XYZ stage of FIG. 11.

"FIG. 14 is a perspective view of the XYZ stage of FIG. 11, showing a first sample cartridge seated in place, and a second sample cartridge to be inserted.

"FIG. 15 is a perspective view of an alternate XYZ stage for an apparatus of FIG. 2, in which a single sample cartridge is to be inserted.

"FIG. 16 is a perspective view of the XYZ stage of FIG. 15, with a sample cartridge inserted.

"FIG. 17 is a schematic flow chart of a first mode of operation of an apparatus of FIG. 2 for detecting mastitis in cattle.

"FIG. 18 illustrates the display of a user interface of an apparatus of FIG. 2 during homing of the optical stage;

"FIG. 19 illustrates the display of a user interface of an apparatus of FIG. 2 for input of animal data or information, particularly the identity of the animal from which the sample(s) are collected;

"FIG. 20 illustrates the display of a user interface of an apparatus of FIG. 2 for input of animal data or information, particularly the type of sample collected, and the number of chambers in the sample cartridge for which sample imaging and analysis is to be carried out;

"FIG. 21 illustrates the display of a user interface of an apparatus of FIG. 2 after homing and/or information entry is completed and when the apparatus is ready to receive the sample cartridge.

"FIG. 22 illustrates the display of a user interface of an apparatus of FIG. 2 during image acquisition and analysis of one of the four separate chambers of a sample cartridge.

"FIG. 23 illustrates the display of a user interface of an apparatus of FIG. 2 after image acquisition and differential leukocyte analysis has been completed. Note that one of the four quarters is indicated as 'positive' for mastitis."

URL and more information on this patent application, see: Bresolin, Stefano; Calderwood, David A.; Heineck, Tobias M.; Newcomb, David; Paul, Chris; Pollard, Jasper N.; Rodriguez, Rodolfo R.; Young, Demetris. Diagnostic Apparatus. Filed July 2, 2013 and posted August 28, 2014. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=4597&p=92&f=G&l=50&d=PG01&S1=20140821.PD.&OS=PD/20140821&RS=PD/20140821

Keywords for this news article include: Circuit Board, Electronics, Microprocessors, Patents.

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Source: Electronics Newsweekly


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