Method and Apparatus for Determining Markers of Health by Analysis of Blood

Abstract

Biomarkers of high blood pressure are measured to identify high blood pressure of the subject based on one or more biomarkers. In many embodiments, the response of the biomarker to blood pressure occurs over the course of at least an hour, such that the high blood pressure identification is based on a cumulative effect of physiology of the subject over a period of time. The methods and apparatus of identifying high blood pressure with biomarkers have the advantage of providing improved treatment of the subject, as the identified biomarker can be related to an effect of the high blood pressure on the subject, such as a biomarker corresponding to central blood pressure. The sample can be subjected to increases in one or more of pressure or temperatures, and changes in the blood sample measured over time.

1 . An apparatus to identify a biomarker from blood of a subject, comprising:
 a processor comprising instructions to identify a biomarker of a blood sample of the subject;   an optically transmissive material having a measurement surface to receive the blood sample;   one or more optical energy detectors coupled to the processor and optically coupled to the measurement surface to measure an amount of the biomarker on the measurement surface;   one or more light sources to generate one or more measurement light beams; and   one or more optical elements arranged to direct the one or more measurement light beams from the one or more light sources to the measurement surface and to direct light from the measurement surface to the one or more optical energy detectors,   wherein the one or more optical elements is configured to measure a surface of one or more red blood cells on the measurement surface with an evanescent wave extending from the measurement surface to the one or more red blood cells on the measurement surface and wherein the biomarker comprises a biomarker of a membrane of a red blood cell.   
     
     
         2 . An apparatus as in  claim 1  wherein the biomarker comprises a plaque biomarker. 
     
     
         3 . An apparatus as in  claim 2  wherein the plaque biomarker comprises a material of one or more of a foam-cell rich plaque, a lipid-rich plaque, or a collagen-rich plaque. 
     
     
         4 . An apparatus as in  claim 1 , wherein the biomarker comprises a blood pressure biomarker. 
     
     
         5 . An apparatus as in  claim 4 , wherein the processor comprises instructions to identify the blood pressure biomarker in response to an evanescent wave measurement of the blood sample on the measurement surface. 
     
     
         6 . An apparatus as in  claim 4 , wherein the processor comprises instructions to identify the blood pressure biomarker in response to a transmission measurement of the blood sample between the measurement surface and an opposing surface. 
     
     
         7 . An apparatus as in  claim 4 , wherein the processor is configured to identify the biomarker in response to the blood sample comprising one or more of red blood cells, serum or plasma, and wherein the apparatus is configured to measure a first component of the blood sample comprising an increased amount of red blood cells in relation to the blood sample and a second component of the blood sample comprising a decreased amount of red blood cells in relation to the blood sample. 
     
     
         8 . An apparatus as in  claim 7 , wherein the processor is configured to measure the first component of the blood sample with one or more of a first evanescent wave measurement or a first optical transmission measurement and to measure the second component with one or more of second evanescent wave measurement or a second optical transmission measurement. 
     
     
         9 . An apparatus as in  claim 8 , wherein the processor is configured to measure the first component of the blood sample with the first evanescent wave measurement and the first optical transmission measurement and to measure the second component with the second evanescent wave measurement and the second optical transmission measurement. 
     
     
         10 .- 11 . (canceled) 
     
     
         12 . An apparatus as in  claim 4 , wherein the apparatus is configured to measure the one or more red blood cells in the presence of an anticoagulant in order to permit a plurality of red blood cells to contact the measurement surface with each of said plurality of red blood cells having an elongate surface extending along an elongate dimension aligned with the measurement surface in order to measure a membrane of said each of the plurality of red blood cells. 
     
     
         13 . An apparatus as in  claim 1 , further comprising:
 a prism comprising the optically transmissive material, the prism comprising the measurement surface to receive the blood sample.   
     
     
         14 . An apparatus as in  claim 13  wherein the prism comprises a Dove prism and wherein the Dove prism is illuminated at a first angle with a first light beam to measure one or more red blood cells on the measurement surface with the evanescent wave of light internally reflected from the measurement surface and wherein the Dove prism is illuminated with a second light beam at a second angle to measure light transmitted through the measurement surface and the blood sample. 
     
     
         15 . An apparatus as in  claim 14 , wherein the Dove prism comprises an elongate axis and a width transverse to the elongate axis and wherein the axis and the measurement surface extend in a first direction and the width extends in a second direction transverse to the first direction. 
     
     
         16 . An apparatus as in  claim 15 , wherein the Dove prism comprises a first inclined surface extending at a first angle oblique to the measurement surface, and a second inclined surface extending a second angle oblique to the measurement surface and wherein the light beam illuminates the surface with total internal reflection to provide the evanescent wave and the light from the evanescent wave is transmitted through the second inclined surface. 
     
     
         17 . An apparatus as in  claim 16 , wherein the measurement surface is located between the first inclined surface and the second inclined surface and wherein an opposing surface extends between the first inclined surface and the second inclined surface opposite the measurement surface and wherein a transmission measurement light beam is transmitted through the opposing surface and the measurement surface to measure transmission through the sample. 
     
     
         18 . An apparatus as in  claim 4 , the processor comprises instructions pressurize the sample and to identify the blood pressure biomarker based on one or more temporal denaturation profiles in response to pressurization of a sample chamber and wherein the optically transmissive material is dimensioned to pressurize the blood sample. 
     
     
         19 . An apparatus as in  claim 4 , wherein the one or more light sources and the one or more detectors and the one or more optical elements are configured to measure chemicals based on optical spectroscopy that are correlated with presence of hypertension and/or correlated with level of blood pressure. 
     
     
         20 . An apparatus as in  claim 4 , wherein the processor comprises one or more instructions to one or more of transform or calibrate biomarker concentration data into a corresponding scale related a systolic and a diastolic pressure during the cardiac cycle, such that the biomarker concentration is transformed from a concentration to a blood pressure in response to measured data of a plurality of subjects. 
     
     
         21 . An apparatus as in  claim 4 , wherein the blood pressure biomarker comprises one or more of adenosine triphosphate, or, one or more transmembrane proteins, one or more proteins of the membrane skeleton, one or more lipids of the red blood cell membrane, a relative ratio of the one or more lipids of the red blood cell membrane, or biomaterial deposited on the surface of the red blood cell membrane. 
     
     
         22 . An apparatus as in  claim 1  wherein the biomarker comprises a spectral signal and wherein the instructions comprise instructions to identify the biomarker in response to the spectral signal. 
     
     
         23 . An apparatus as in  claim 1  wherein the biomarker comprises a plurality of biomarkers comprising a spectral signal and wherein the instructions comprise instructions to identify the plurality of biomarkers in response to the spectral signal. 
     
     
         24 . An apparatus as in  claim 1 , wherein the biomarker comprises one or more of a protein, a lipid, a high density lipoprotein, a low density lipoprotein, membrane protein, a transmembrane protein, or a spectrin network, and wherein spectra of the biomarker comprise one or more of an Amide I peak, an Amide II peak, a Carboxylate peak, or an Amide III band. 
     
     
         25 . An apparatus to identify a biomarker from blood of a subject, comprising:
 a processor comprising instructions to identify a biomarker of a blood sample of the subject,   wherein the biomarker comprises one or more of a protein, a lipid, a high density lipoprotein, a low density lipoprotein, membrane protein, a transmembrane protein, or a spectrin network, and wherein spectra of the biomarker comprise one or more of an Amide I peak, an Amide II peak, a Carboxylate peak, or an Amide III band, and   wherein the Amide I peak, the Amide II peak, and the Amide III band correspond to an alpha helix of the biomarker, a beta sheet of the biomarker, and disordered protein of the biomarker, respectively.   
     
     
         26 . An apparatus as in  claim 25  wherein the instructions comprise instructions to identify the biomarker in response to one or more of the Amide I peak, the Amide II peak, the Carboxylate peak, or the Amide III band. 
     
     
         27 . An apparatus as in  claim 1  wherein the biomarker comprises a spectral signal and wherein the instructions comprise instructions to determine a plurality of factors in response to the spectral signal. 
     
     
         28 .- 32 . (canceled) 
     
     
         33 . An apparatus as in  claim 27 , wherein the plurality of factors comprises a plurality of multivariate curve resolution factors or a plurality of multi-component analysis factors. 
     
     
         34 . An apparatus as in  claim 27  wherein the instructions comprise instructions to identify the biomarker in response to a relationship among a plurality of factors determined in response to the spectral signal. 
     
     
         35 .- 47 . (canceled) 
     
     
         48 . The apparatus of  claim 1 , further comprising a sample container to receive the blood sample of the subject. 
     
     
         49 . An apparatus as in  claim 48 , wherein the sample container extends in a vertical direction a distance sufficient to gravimetrically separate red blood cells from serum of the blood sample. 
     
     
         50 . An apparatus as in  claim 49 , wherein the sample container extends in a vertical direction a distance sufficient to wash the red blood cells when the red blood cells separate from the serum and wherein the container comprises a volume of a solution sufficient to wash the red blood cells. 
     
     
         51 .- 53 . (canceled) 
     
     
         54 . An apparatus as in  claim 48 , wherein the sample container comprises a removable container comprising a waveguide to introduce the evanescent wave into a lower portion of the removable container, wherein the waveguide comprises the optically transmissive material having the measurement surface. 
     
     
         55 .- 72 . (canceled) 
     
     
         73 . An apparatus as in  claim 1 , wherein the processor comprises instructions to identify the biomarker in response to a time series of spectra of the blood sample as water is removed from the blood sample. 
     
     
         74 . (canceled) 
     
     
         75 . An apparatus as in  claim 1 , wherein the processor comprises instructions to identify the biomarker with water at least partially removed from the blood sample to inhibit a water signal of the blood sample and to inhibit lysing of the one or more red blood cells, the processor comprising instructions to measure the blood sample with the red blood cell membranes substantially intact and adsorbed on the measurement surface with the water at least partially removed from the blood sample. 
     
     
         76 .- 168 . (canceled)