Immune and oxygen system measuring and drug screening method and apparatus

• US 9,140,712 B2
• Filed: 04/27/2011
• Issued: 09/22/2015
• Est. Priority Date: 04/27/2010
• Status: Active Grant

• Current Assignee: Samir Sofer
• Original Assignee: Samir Sofer
• Inventors: Sofer, Samir
• Primary Examiner(s): Chen, Tse
• Assistant Examiner(s): Liu, Chu Chuan (JJ)
• Application Number:
  US13/695,150
• Publication Number:
  US 20130041239A1
• Time in Patent Office: 1,609 Days
• Field of Search: 600/300, 600/309, 600/310, 600/345, 600/347, 600/365, 600/473, 600/476, 435/2, 435/5, 435/288.7, 73/310.5, 73/232, 422 8201- 8209, 422 83- 84, 422/98, 604 19- 24, 604/48
• US Class Current: 1/1
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 33/22 Boron compounds
• CPC Class Codes: A61K 35/14 Blood; Artificial blood perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42
• CPC Class Codes: G01N 33/48 Biological material, e.g. blood, urine G01N33/02, G01N33/26, G01N33/44, G01N33/46 take precedence; Haemocytometers counting blood corpuscules distributed over a surface by scanning the surface G06M11/02
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

Method and apparatus for monitoring health as related to immune system function, and for measuring the effects of toxins and other stresses. A method for pre-screening drugs for the pharmaceutical pipeline. A method for using an Immunogram as a research tool. A method for preparing compounds or drugs for treatment, therapy, or cure of diseases.

Claims

1. A method for determining ROX and BOX, comprising the steps of:

providing a first sensor and a second sensor;

providing a sample including an amount of bodily material, said sample including molecular oxygen and nitric oxide, wherein said first sensor is adapted to sense said molecular oxygen and to send a signal related to the amount of said molecular oxygen, and wherein said second sensor is adapted to sense said molecular oxygen and said nitric oxide and to send a signal related to the amount of said molecular oxygen and said nitric oxide;

providing a processor in electrical connection with said first and second sensors and responsive to said signals received from said first and second sensors, and wherein said processor is adapted to determine the amount of said molecular oxygen and said nitric oxide from the difference between said first sensor signal and said second sensor signal;

sensing by said first sensor molecular oxygen and by said second sensor molecular oxygen and nitric oxide present in said sample;

then sending by said first and second sensors a first set of signals to said processor at a first point in time;

determining by said processor from said first set of signals baseline values for said molecular oxygen and nitric oxide;

introducing a first stress into said sample, wherein said first stress is a stress that is administered over time;

then sensing over time with said first and second sensors said molecular oxygen and said nitric oxide present in said stressed sample;

then sending by said first and second sensors a second set of signals to said processor at a second point in time;

then sending by said first and second sensors a third set of signals to said processor at third point in time;

determining by said processor from said second set of signals BOX values for said molecular oxygen and said nitric oxide, which are a measurement of a decrease in said molecular oxygen and said nitric oxide in said sample as compared to said baseline values; and

determining by said processor from said third set of signals ROX values for said molecular oxygen and said nitric oxide, which are a measurement of an increase in said molecular oxygen and said nitric oxide in said sample as compared to said BOX values, respectively, wherein said increase in said nitric oxide is determined from the difference in said first sensor signal and said second sensor signal;

introducing a second stress into said stressed sample;

then sensing over time with said first and second sensors said molecular oxygen and said nitric oxygen;

then sending by said first and second sensors a fourth set of signals to said processor at a fourth point in time;

determining a SOX value, which is a sharp increase in either said molecular oxygen or said nitric oxide following said introduction of said second stress in said stressed sample as compared to said ROX value for said molecular oxygen and said nitric oxide, respectively; and

administering said sample to a subject following said determination of said SOX value.

2. The method as recited in claim 1, wherein said first sensor is an optical probe and said second sensor is a membrane probe.

3. The method as recited in claim 1, further comprising the steps of providing a cell and introducing said sample into said cell.

4. The method as recited in claim 1, further comprising the step of determining a turning point for said amount of bodily material in said sample.

5. The method as recited in claim 1, wherein said bodily material is blood and wherein a higher optical probe signal of said third set of signals indicates said ROX value for said molecular oxygen, and wherein a membrane-based sensor signal of said third set of signals higher than said baseline value indicates a ROX value for said nitric oxide.

6. An apparatus for measuring ROX and BOX in a sample having an amount of molecular oxygen and nitric oxide and subjected to a stress source, comprising:

an optical probe and a membrane probe in a cell that are operatively connected to a processor, wherein said optical probe is adapted to detect unbound molecular oxygen, which is molecular oxygen that is not bound to hemoglobin or white blood cells, in a sample of bodily material contained in said cell, and to deliver a signal over time as to the amount of said unbound molecular oxygen from said sample to said processor through a first data line, wherein said membrane probe is adapted to detect unbound molecular oxygen and unbound nitric oxide, which is nitric oxide that is not bound to hemoglobin or white blood cells, in said sample of bodily material and to deliver signals over time as to the amount of said unbound molecular oxygen and unbound nitric oxide from said sample of bodily material to said processor through a second data line, wherein said processor is adapted to compute a BOX, ROX and SOX values for molecular oxygen and nitric oxide in said sample of bodily material, wherein said BOX value for each of said molecular oxygen and said nitric oxide is a measurement of the rate at which said unbound molecular oxygen and said unbound nitric oxide become bundled, that is attached to white blood cells and thus undetectable by said optical and membrane probes, respectively, based on a detected decrease in said unbound oxygen and said unbound nitric oxide over time when said sample is subjected to a stress by a stress source, wherein said ROX value for each said molecular oxygen and said nitric oxide is a measurement of the amount of bundled molecular oxygen and bundled nitric oxide, that is molecular oxygen and nitric oxide that were attached to white blood cells and thus undetectable by said optical and membrane probes, respectively, based on a detected increase in said unbound molecular oxygen and said unbound nitric oxide at any point in time after said BOX value is computed, wherein said processor computes said ROX value for said nitric oxide by determining the difference between said optical probe signal and said membrane probe signal, wherein said SOX value is a measurement of a sharp increase in said nitric oxide or said molecular oxygen as compared to said ROX value for nitric oxide and molecular oxygen at any point in time after said BOX value is computed, and wherein upon detection of said sharp increase, said bodily material is administered to a subject.

7. The apparatus as recited in claim 6, wherein said membrane probe is a polarographic oxygen electrode.

8. The apparatus as recited in claim 6, wherein said optical probe is a ruthenium-coated fiber optical light emitting diode probe.

9. The apparatus as recited in claim 6, wherein said stress source includes at least one full continuous stress, at least one partial stress, or at least one stress administered more than once over time.

10. The apparatus as recited in claim 6, wherein said stress source is a physical stress.

11. The apparatus as recited in claim 6, wherein said stress source is a chemical stress.

12. The apparatus as recited in claim 6, wherein said bodily material is blood and wherein a higher optical probe signal as compared to a membrane probe signal indicates said ROX value for said molecular oxygen, and wherein a higher membrane probe signal as compared to an optical probe signal indicates said ROX value for said bundled nitric oxide.

13. A method for controlling the concentrations of ROX and BOX, comprising the steps of:

providing at least one optical sensor and one membrane sensor that are operatively connected to a processor;

providing a sample including an amount of bodily material with an amount of molecular oxygen and nitric oxide, said optical sensor adapted to detect said molecular oxygen over time and to send a signal to said processor as to the amount of said molecular oxygen an said membrane sensor adapted to detect said molecular oxygen and said nitric oxide over time and to send signals to said processor over time as to the amount of said molecular oxygen and said nitric oxide;

determining by said processor with said optical and membrane sensors baseline values for said amount of said molecular oxygen and said nitric oxide at a first point in time;

providing a stress source;

introducing by said stress source a stress into said sample after said baseline values are determined;

determining by said processor with said optical and membrane sensors BOX values for said molecular oxygen and said nitric oxide at a second point in time, said BOX values being a measurement of the rate at which said molecular oxygen and said nitric oxide is consumed, respectively, in said sample after said stress is introduced;

determining by said processor with said optical and membrane sensors ROX values for said molecular oxygen and said nitric oxide following said second point in time, said ROX values being an increase in the amount of said molecular oxygen and said nitric oxide, respectively, following said determination of said BOX values, wherein said ROX values for said molecular oxygen and said nitric oxide are determined from the difference in said optical sensor signal and said membrane sensor signal;

determining by said processor with said optical and membrane sensors a SOX value for said molecular oxygen or said nitric oxide following said second point in time, said SOX value being a sharp increase in said molecular oxygen or said nitric oxide as compared to said ROX values for said molecular oxygen and nitric oxide, respectively;

introducing a controlling or blocking material into said sample, wherein said controlling material is adapted to alter either said ROX values or said BOX values in said sample; and

administering said sample into a subject upon said determination by said processor of said SOX value.

14. A method for predicting the onset of rejection to a treatment material, comprising the steps of:

providing an optical sensor and a membrane sensor connected to a processor;

providing a sample from a patient intending to undergo treatment by a treatment material, including an amount of bodily material with an amount of molecular oxygen and nitric oxide, wherein said optical sensor is adapted to sense molecular oxygen over time and to send a series of signals over time to said processor relating to said amount of said molecular oxygen, and wherein said membrane sensor is adapted to sense molecular oxygen and nitric oxide over time and to send a series of signals over time to said processor relating to said amount of said molecular oxygen and said nitric oxide;

determining by said processor with said optical and membrane sensors baseline values for said molecular oxygen and nitric oxide;

introducing a stress into said sample following said determination of said baseline values, wherein said stress includes an amount of treatment material, and wherein said treatment material is a material that is integral to said treatment;

determining by said processor with said optical and membrane sensors BOX values for said molecular oxygen and nitric oxide in said sample, which are a measurement of the consumption of said amount of molecular oxygen and nitric oxide, respectively, following said introduction of said stress, in said sample;

determining by said processor with said optical an membrane sensors ROX values for said molecular oxygen and said nitric oxide, which are a measurement of an increase in said molecular oxygen and said nitric oxide, wherein said ROX value for each said molecular oxygen and said nitric oxide is determined from the difference in said optical sensor signal and said membrane sensor signal at any point in time following said determination of said BOX values in said sample;

determining by said processor with said optical and membrane sensors a SOX value for said molecular oxygen or said nitric oxide following said second point in time, said SOX value being a sharp increase in said molecular oxygen or said nitric oxide as compared to said ROX values for said molecular oxygen and said nitric oxide, respectively;

predicting the onset of rejection to said treatment material, wherein said predicting step is done by comparing said BOX and ROX values to the BOX and ROX values based on data obtained from individuals other than said patient, wherein said ROX and BOX values of said patient are outside of the range of said ROX and BOX values of said individuals; and

administering said sample to said patient upon said determining by said processor of said SOX value.

15. An apparatus for measuring ROX and BOX in a sample having an amount of molecular oxygen and nitric oxide and subjected to a stress source, comprising:

a first sensor and a second sensor in a cell that are operatively connected to a processor, wherein said first sensor is adapted to detect unbound molecular oxygen, which is molecular oxygen that is not bound to hemoglobin or white blood cells, in a sample contained in said cell, well or structure, and to deliver a signal over time as to the amount of said unbound molecular oxygen from said sample to said processor through a first data line, wherein said second sensor is adapted to detect unbound molecular oxygen and unbound nitric oxide, which is nitric oxide that is not bound to hemoglobin or white blood cells, in said sample and to deliver signals over time as to the amount of said unbound molecular oxygen and unbound nitric oxide from said sample to said processor through a second data line, wherein said processor is adapted to compute BOX, ROX and SOX values for molecular oxygen and nitric oxide in said sample, respectively, wherein said BOX value for each said molecular oxygen and said nitric oxide is a measurement of the rate said molecular oxygen and said nitric oxide become bundled by white blood cells in said sample of blood based on a detected decrease in said unbound oxygen and said unbound nitric oxide over time when said sample is subjected to a stress by a stress source, wherein said ROX value for each said molecular oxygen and nitric oxide is a measurement of the amount of bundled molecular oxygen and bundled nitric oxide in said sample based on a detected increase in said unbound molecular oxygen and said unbound nitric oxide at any point in time after said BOX value is computed, wherein said processor computes said ROX values for said molecular oxygen and said nitric oxide by determining the difference between said first sensor signal and said second sensor signal, wherein said SOX value is a measurement of a sharp increase in said nitric oxide or molecular oxygen as compared to said ROX value for nitric oxide and molecular oxygen at any point in time after said BOX value is computed, and wherein upon detection of said sharp increase, said sample is administered to a subject.