James G Downward

20010023077, Sep 20, 2001

Apr 12, 2001

09/833998

Judith Erb - Ann Arbor MI, US
James Downward - Ann Arbor MI, US
John Erb-Downward - Ann Arbor MI, US
Otho Ulrich - Ann Arbor MI, US

G01N033/543

436/518000

A method and apparatus for measuring binding between a plurality of molecules of a first type and a plurality of molecules of a second type is presented. Apparatus utilizes a sensor possessing a waveguide to which have been attached in close proximity to its surface, features resembling molecules of said first type. Light is injected into said waveguide so as to produce an evanescent field at its surface. Molecules of said second type are tagged with a tag belonging to that class of chemicals which alters a characteristic of light, when said light passes through said chemical tag. Apparatus utilizes a rapid means of monitoring the change in optical signal coming from said waveguide as binding proceeds between tagged molecules of type 2 and the feature resembling molecules of type 1 on said waveguide. This allows direct measurement of binding and dissociation rates between the two types of molecules. Methods are provided whereby such data may be used to compute affinity constants, binding activity, complex affinity constants resulting from cooperativity, and kinetic parameters for the molecular pair. Preferred embodiments of the invention illustrate application of the method and apparatus to measuring binding between biological receptors and their nuclear response elements, and the use of this type of measurement for assessment of the activity of hormonal mimics present in a sample, for evaluation of pharmaceuticals intended to treat hormone dependent cancers, and for evaluation of tissue biopsy samples to detect mutant forms of the p53 protein.

20010034036, Oct 25, 2001

Jun 19, 2001

09/885321

Judith Erb - Ann Arbor MI, US
Nallaperumal Chidambaram - Dearborn Heights MI, US
James Downward - Ann Arbor MI, US

G01N033/53
C12M001/34

435/007100, 435/287200

A testing apparatus having an absorbent matrix , including a membrane which contains a plurality of counter-ions Chromionophore (or fluorionophore)s and affinophores compete to carry ions into the membrane and neutralize the charge of the counterions Biological recognition molecules bind to a portion of the affinophores and prevent them from entering the membrane thereby allowing more chromionophore (or fluorionophore)s to enter the membrane The portion of affinophores bound to the biological recognition molecules is inversely proportional to the amount or concentration of analyte occurring within the solution or medium The result of this is that the color of the membrane-covered matrix changes in a manner related to the concentration of the analyte. One application of this apparatus is a strip test for prediction of ovulation.

20020137055, Sep 26, 2002

Jul 20, 2001

09/910628

Judith Erb - Ann Arbor MI, US
James Downward - Ann Arbor MI, US
John Erb-Downward - Ann Arbor MI, US
James Witliff - Louisville KY, US

C12Q001/68

435/006000

A method and apparatus for measuring binding between a plurality of molecules of a biological receptor protein and a plurality of molecules of a type which binds to said biological receptor is presented. Apparatus utilizes a sensor possessing a waveguide to which have been attached in close proximity to its surface, features resembling molecules having binding affinity for said biological receptor. Light is injected into said waveguide so as to produce an evanescent field at its surface. Molecules of receptor protein are tagged with a tag belonging to that class of chemicals which alters a characteristic of light, when said light passes through said chemical tag. Apparatus utilizes a rapid means of monitoring the change in optical signal coming from the waveguide as binding proceeds between tagged receptor protein and the binding molecular feature of the waveguide. This allows direct measurement of binding and dissociation rates between the receptor and the binding feature of the waveguide. By using a waveguide having a feature resembling a ligand for the receptor, the potential hormonal activity of a test substance may be evaluated from its ability to compete with the waveguide for binding with the receptor. The effect of a test compound on binding of receptor protein to a subsequent element in a hormonal signal transduction mechanism is evaluated by measuring the impact of the test compound on binding between receptor protein and a feature resembling said next element of the signal transduction mechanism. Methods are provided whereby such data may be used to compute affinity constants, binding activity, complex affinity constants resulting from cooperativity, and kinetic parameters for the receptor and test ligand and for the receptor and the next element of the signal transduction mechanism. Preferred embodiments of the invention illustrate application of the method and apparatus to measuring binding between biological receptors and their nuclear response elements, and the use of this type of measurement for assessment of the activity of estrogen mimics present in a test sample, and for evaluation of pharmaceuticals intended to treat hormone dependent cancers.

20030008314, Jan 9, 2003

Jun 28, 2002

10/186151

Eric Priuska - Ann Arbor MI, US
Richard Smith - Ann Arbor MI, US
Judith Erb - Ann Arbor MI, US
James Downward - Ann Arbor MI, US
Otho Ulrich - Ann Arbor MI, US

C12Q001/68
G01N033/53
G01N033/542

435/006000, 435/007900

A method for performing a rapid, homogenous assays for monitoring the reactions of a binding target, by immobilizing a fluorescent-capable chelate complex that is derivatized so as to posses recognition binding ligands, labeling the complex with a labeled second chelator that is added to the assay thereby forming a fluorescent mixed chelate, and measuring the fluorescent mixed chelate, whereby the measurement of the label enable monitoring of the reaction of the binding target. A rapid assay for performing the above method including a first chelating molecule, a fluorescent-capable ion complexed with the first chelating molecule, a second chelating molecule for reacting with the fluorescent-capable ion complexed with the first chelating molecule, and a measuring device for measuring fluorescent resulting from the second is chelating molecule reacting with the fluorescent-capable ion complexed with the first chelating molecule. A biosensor for monitoring molecular interactions between receptors, including a biosensor having attached thereto a fluorescent-capable ion complexed with a first chelating molecule, whereby upon exposure to a second chelating molecule said complex becomes fluorescent is also provided.

20050181432, Aug 18, 2005

Mar 30, 2005

11/095971

Eric Priuska - Ann Arbor MI, US
Richard Smith - Ann Arbor MI, US
Judith Erb - Ann Arbor MI, US
James Downward - Ann Arbor MI, US
Otho Ulrich - Ann Arbor MI, US

C12Q001/68
G01N033/53

435006000, 435007100

A method for performing a rapid, homogenous assays for monitoring the reactions of a binding target, by immobilizing a fluorescent-capable chelate complex that is derivatized so as to posses recognition binding ligands, labeling the complex with a labeled second chelator that is added to the assay thereby forming a fluorescent mixed chelate, and measuring the fluorescent mixed chelate, whereby the measurement of the label enable monitoring of the reaction of the binding target. A rapid assay for performing the above method including a first chelating molecule, a fluorescent-capable ion complexed with the first chelating molecule, a second chelating molecule for reacting with the fluorescent-capable ion complexed with the first chelating molecule, and a measuring device for measuring fluorescent resulting from the second chelating molecule reacting with the fluorescent-capable ion complexed with the first chelating molecule. A biosensor for monitoring molecular interactions between receptors, including a biosensor having attached thereto a fluorescent-capable ion complexed with a first chelating molecule, whereby upon exposure to a second chelating molecule said complex becomes fluorescent is also provided.

20070014692, Jan 18, 2007

Jul 28, 2006

11/495047

Judith Erb - Ann Arbor MI, US
James Downward - Ann Arbor MI, US
Otho Ulrich - Ann Arbor MI, US

G01N 21/64

422082110

A method and apparatus for measuring binding between a plurality of molecules of a first type and a plurality of molecules of a second type is presented. Apparatus utilizes a sensor possessing a waveguide to which have been attached in close proximity to its surface, features resembling molecules of said first type. Light is injected into said waveguide so as to produce an evanescent field at its surface. Molecules of said second type are tagged with a tag belonging to that class of chemicals which alters a characteristic of light, when said light passes through said chemical tag. Apparatus utilizes a rapid means of monitoring the change in optical signal coming from said waveguide as binding proceeds between tagged molecules of type 2 and the feature resembling molecules of type 1 on said waveguide. This allows direct measurement of binding and dissociation rates between the two types of molecules. Methods are provided whereby such data may be used to compute affinity constants, binding activity, complex affinity constants resulting from cooperativity, and kinetic parameters for the molecular pair. Preferred embodiments of the invention illustrate application of the method and apparatus to measuring binding between biological receptors and their nuclear response elements, and the use of this type of measurement for assessment of the activity of hormonal mimics present in a sample, for evaluation of pharmaceuticals intended to treat hormone dependent cancers, and for evaluation of tissue biopsy samples to detect mutant forms of the p53 protein.

20100284863, Nov 11, 2010

Mar 17, 2008

12/049934

James G. Downward - Ann Arbor MI, US
Judith L. Erb - Ann Arbor MI, US
Daniel P. Schmidt - Dexter MI, US

G01N 21/63

422 8208, 422 8205

Some embodiments of the invention comprise a biosensor cartridge which optically, fluidically, and/or mechanically couples to an evanescent sensing measurement apparatus having annularizing illumination elements, said biosensor cartridge and measurement apparatus being used for detecting the presence of chemically or biologically active substances binding to said biosensor present within an aqueous media, such as and without limitation, the presence of specific proteins in blood or urine. Some embodiments comprise an integrated biosensor cartridge having a flow channel and a plurality of storage cavities, fluid flow in the cartridge controlled by valving mechanisms for directing a plurality of fluids through the cartridge, the order and amounts of such fluids passing through the cartridge being externally controlled and required for the detection and measurement of specific chemically or biologically active substances.

52892670, Feb 22, 1994

Oct 4, 1991

7/770885

Garland E. Busch - Milan MI
James G. Downward - Ann Arbor MI
Paul G. Gottschalk - Ann Arbor MI
Theodore B. Ladewski - Ann Arbor MI
Charles D. Lysogorski - Dexter MI

KMS Fusion, Inc. - Ann Arbor MI

G01B 1100
G01J 102

356394

A method and system for gauging deviations of a surface of a test part from a preselected nominal surface profile is disclosed. The system includes a support having a master surface that is substantially a matched or mating surface of the nominal surface profile of the test part and a thin layer of an attenuating medium such as a dye liquid between the master and test surfaces. Electromagnetic radiation is directed through the support and master surface and through the attenuating layer onto the reflective surface of the test part. An image sensor such as a camera is positioned to receive an image of the radiation reflected by the test part surface back through the attenuating layer and support, with the intensity of such radiation across the image varying as a function of the deviation of the test part surface from the nominal surface profile. The sensor output is digitized to form a series of digital signals indicative of the intensity of radiation associated with each location of the reflected image, and the digitized pixel signals are stored in digital electronic memory and/or displayed on a screen. Computer programming corrects the digitized intensity signals for sensor gain, bias and variations in part reflectivity, and presents a quantitative measurement of the deviations in test surface profile from the master surface profile over the entire surface being measured.