CA2449621C - System and method for noninvasive hematocrit monitoring - Google Patents

Abstract

A system for determining the hematocrit transcutaneously and noninvasively. Disclosed are a finger clip assembly (6) and an earlobe clip assembly (10), each including at least a pair of emitters (1,2) and a photodiode (3) in appropriate alignment to enable operation in either a transmittion mode or a reflectance mode. At least two, and preferably three, predetermined wavelengths of light are passed onto or through body tissues such as the finger (7), earlobe (11 ), or scalp, etc. and the extinction of each wavelength is detected. Mathematical manipulation of the detected values compensates for the effects of body tissue and fluid and determines the hematocrit value. If a fourth wavelength of light is used which is extinguished substantially differently by oxyhemoglobin and reduced hemoglobin and which is not substantially extinguished by plasma, then the blood oxygen saturation value, is determinable independently of the hematocrit value. It is also within the scope of the present invention to detect and analyze multiple wavelengths using a logarithmic DC analysis technique. In this embodiment, a pulse wave is not required. Hence, this embodiment may be utilized in states of low blood pressure or low blood flow.

Description

. - -. . -. . - .. :.. --SYSTEM A_ND~.. METHOD.:.FOR. NONINVASI~7E .
HENLATOCRIT MONITORING .
' ... .. , BACKGI30UND
. 1. The Field of the Invention.
This invention relates to systems and methods..for .
noW nvasively.measuring one. or m~re.biologic constituent values. More particularly, the ;present invention relates to noninvasive spectrophotometric systyems and methods for .'15 ~~quantitatively ~~arici ~'con~'inuous'ly imoniior'iiig the"~ematoerit' ""
.and : other blood -parameters :of .a s ub~.e.ct.,.. . .. . ...

2. The Prior Art.
Modern medical practice utilizes a number of procedures and indicators to assess a patient's condition.
One of these indicators is the patient's hematocrit.
Hematocrit (often abbreviated as Hct) is the volume,' expressed as a percentage, of the patient's blood which is occupied by red corpuscles (commonly referred to as red blood cells).
- Human blood consists principally of liquid plasma (which is comprised of over 90 o water with more than 300 other constituents such as proteins, lipids, salts, etc.) and three different corpuscles. 'The three corpuscles found in blood are red corpuscles, white corpuscles, and platelets.
The chief function of red corpuscles is to carry oxygen from the lungs to the body tissues and carbon dioxide from the tissues to the lungs. This critical life supporting function is made possible by hemoglobin which is the principal active constituent of red corpuscles. In the lungs, hemoglobin rapidly absorbs oxygen to form oxyhemoglobin which gives it a bright scarlet color. As the red corpuscles travel to the tissues, the oxyhemoglobin D
_ .
~" ..- ~ releases .,oxygen, i . e.. ,. is "reduced, aiid . the hemogl~o'bin ~turiis~;'~. y ', a dark red color.

The oxygen, transportation functions of the body rely ., , ' essentially eriti.rely on:: the presence of hemoglobin. in ahe ~ _ ..
, red cbrpuscles: - 'Red~'corpuscles ~ greatly~~: outnu~nber~~,other'.
~: _~

corpuscles, being about 7.o0ytimes greater than .the number. of . .

white corpuscles in a healthy human subject:

Medical professionals routinely desire. to.knaw the . hematocrit,of a patient. In.order to determine hematocrit using any of the techniques available to date, it is necessary to draw a sample of blood by.~uncturing a vein or ~~invading ~~a capillary. ~I'hen~; ~" iisiiig -~a~~"widely 'accepted technique-, - the- .s.amp~.e :.of.. bla~od ,is... subj ected.
to. ~.~ "high speed ,._ : r centrifuge treatment for several minutes (ela., 7 or more minutes). The centrifuging process, if properly carried out, separates the corpuscles into a packed mass. The volume occupied by the packed corpuscles, expressed as a -percentage of the total volume of the plasma/corpuscle combination, is taken as the hematocrit.

- It will be appreciated that the centrifuge process provides a hematocrit value which includes all corpuscles, -- not just red corpuscles. Nevertheless, the vastly greater numbers of red corpuscles in a healthy subject allows the hematocrit value obtained by the centrifuge process to be clinically usable'in such healthy subjects. Nevertheless, in subjects with low hematocrit or dramatically high white corpuscle content, it may be desirable to diminish the effect of the non-red corpuscles when obtaining an hematocrit value.

There have been various techniques and devices introduced which have automated and increased the precision of obtaining a hematocrit value. Nevertheless, all the previously available techniques have one or more drawbacks.

Specifically, the previously available techniques all require that a sample of blood be withdrawn from the _ -3-patient-.f, or - in-vitro. analysis.,.. Ariy ..invasion -of rthe' siibj ect ~to obtain , blood is - . accompanied ~ ~by the' 7problems of inconvenience, stress, and discomfort imposed upon the subject and- also v the risks which are" always present :when ~._ .. .
- v ~ - 5' Y the body ~is- .invaded. ~ - DraW'ing.,blood-ako .createsL.certain~.
contamination ' risks -'. to the paramedical ~ .professional.
Moreover, even in a setting where obtaining a blood sample does not impose any - ~addit~ional problems., e...a.. , .during .
surgery, the previ~usly available techniques reqwire a delay between the time that the ,sample is drawn and the.
hematocrit value is obtained. Still .further, none of the previously-avai~.abhe techri~iques'alToW coiltiriudus iaohittiririt~"
.. .of ..a.
subject'a.:.hemato:c.rit,...,as...Might;..,be:..desirable..~.du.,~irig.. .
some surgical procedures ar intensive care treatment, but require the periodic withdrawal and processing of blood samples.
In view of the drawbacks inherent in the available art dealing with invasive hematocrit determinations, it would' be an advance in the art to noninvasively and quantitatively determine a subject's hematocrit value. It would also be an advance in the art to provide a system and - method for noninvasive hematocrit monitoring which can be applied to a plurality-of body parts, and which utilizes electromagnetic emissions as an hematocrit information carrier. It would be another advance in the art to provide a system and method which can provide both immediate and continuous hematocrit information for a subject. It would be yet another advance to provide repeatable and reliable systems for noninvasive monitoring of a subject's hematocrit. It wauld be still another advance in the art to noninvasively and accurately determine a subject's blood oxygen saturation while accounting for the pati'ent's low or varying hematocrit and/or under conditions of low perfusion. -_ _4_ . . . . : ... .. ' ~. .. . . : .; .. _-.: BRIEF . ST ..TMMARY ~ AND OBJEC'rS~
OF~ 'THE~~~ ZNV~NTIOf~..'- ' ", ' ': ~ < . . -: ..
The present invention ~ misdirected ~ toapparatus and methods for determining biologic; constituent values, such . . as the w liematocrit: . va~hx~., :~ .. trans~u~aneous.ly . , :and -. . ...
~ ~ .noninvasivel~~.~ ~. ~ ~TYiis.~ isv achxevecl.: ~by ~ passing..; at ., lease.. t~ao .. ~ ..~. ' wavelengths ~ -of ~ light onto-. or through ~ body : tissues ':such - asw :- _ the finger; earlobe; or.scal.p; lets. and then compensating for the effects body' tissue and fluid.:.effects.. '. As: used. .
herein, the term biologic constituent includes proteins, red cells , metabolites , drugs, c,ytochromes, hormones,.etc. .
In one embodiment within the scope of the present iriventi~on',"t~iev"wavelengths of light 'are welected to~'be'nea~rw .. .. . . .. or ...at.....:the.,. . iso..bestic.. .:points.. -c~~.
,,.reduced., _ hemoglobin, and' ,_ .
oxyhemoglobin to eliminate the effects of variable blood oxygenation. At an isobestic wavelength, the extinction coefficient, e, is the same for both reduced and oxygenated hemoglobin. Thus, at isobestic~wavelengths, the amount of light absorption is independent of the amount of-oxygenated or reduced hemoglobin in the red cells.
Means are provided for delivering and detecting those wavelengths of light and for analyzing the light intensities. The sensing and radiation emitting elements are preferably spatially arranged to allow ease of use and' to be accessible to a,patient's exterior body parts. The configuration of the sensing and emitting ele~uents is 'important to give optimum repeatability of the signals and data derived therefrom.
Memory and calculation means are included which are capable of storing, manipulating, and displaying the detected signals i1~ a variety of ways. For instance, the continuous pulse wave contour, the pulse rate value, the hematocrit value and the continuous analog hematocrit curve in real time, the hematocrit-independent oxygen saturation value, and the oxygen content value of the blood, all as m _. _5_ .-- digital,-vahues".or as co~tinuous.analog curve~,:,'in real: ~t~mp'~
,. : .' ......~'..:':: . ~.' h.. ... ~.,..... ,.... ;. ._.,..~... ., .. ~~ ..
~ .... . ., . ,..~ . . ..
are capably of being displayed.
An important advantage of monitoring and analyzing w _~ each v~ ind,ividiral--- ~ :.pulsatile~: rsyiial ~. ~is- - ~ that w a~xer~i~g.irig ...
' -algorithms .inay~.~=be.'perfo'rmedv.for. identifying- -andvreject~.ng= '.
erroneous data . , . - In y addition, such , techniques also y impvove repeatability. ' ~ v . - -.
Another significant~advantage of the present 'invention.
- is the capability. of monitoring multiple wavelengths (including nonisobestic wavelengths) for the simultaneous real time computation and display .~f the -hematocrit i~ndependent~ oxygen -saturation va:Lue:'~ ' Techiiiqiies iii-"prior' '~'"
.. . .. .ai , .... . ox.imet-ry . ...,have'.. . :a~Z.l . .. .suffered.
:.inaccuracies. .. . dare .... . tp ,.., _. .
hematocrit sensitivities.
Rather than apply AC-DC cancellation techniques only, it is also within the° scope of the present invention to detect and analyze multiple wavelengths using a logarithmic "
DC analysis technique. In this embodiment, a pulse wave is-not required. Hence, this embodiment may be utilized in states of low blood pressure or low blood flow.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a perspective 'view of a first presently preferred embodiment of the present invention.
Figure 1A is an enlarged cross sectional view of the body part (finger) and system~components represented in Figure 1 used in a transmission mode.
Figure 1B is an enlarged cross sectional view of the body part (finger) and associated system components represented in Figure 1 used in a reflective mode.
Figure 2 is a chart showing the optical absorption coefficients of oxyhemoglobin (Hb02), reduced hemoglobin (Hb), .and water (H2o) versus wavelength.

b - -s-. . . . Y.. . ~. Figure. _. 3 ~~ is. a chart showing .. the. relationshiP_ between the' extinction coefficient ~of Tight. at~ three different .~
wavelengths versus hematocrit for whole blood.
' ., , ~ . ,-, y _ - ,~ , . ~Figure~ 4 ~ is a ~ chatty showing : ahe relationship'.. betwe~eri :, . ... , .
' S the ratio . o~ .the ~ extinction coeff ic~ients~ of twow rays having differing - ra~vei~engtlis- 'versus,. ~hematocrit:; : . .
Figures SA-5E provide a flaw chart showing the steps carried out during one presently preverred mEthod of the present ,invention, using the pulsatile component of the l0 subject's blood flow to provide accurate hematocrit and blood oxygen saturation values: -~Figure ~6 ~is~~ a~~~perspective view- of '~a- secoiid~ presently ' -. . - . - . pr~efe.rred~.. ~sys~tem of...t;he,-.,present : invention. wh.i.ch is,. applied. .
to the ear and includes structures to squeeze out the blood 15 to blanch the ear tissues.
Figure 6A is ari enlarged cross sectional view of the ear and system components represented in Figure 6.
Figure ? provides a detailed schematic diagram of the-low level sensor circuitry included in the presently 20 preferred system of the present invention.
Figures 8A-8C provide a detailed schematic diagram digital section circuitry included in the presently preferred system of the present invention.
Figures 9A-9D provide a detailed schematic diagram of 25 the analog section circuitry included in the presently preferred system of the present invention.
Figures l0A-lOC provide a detailed schematic diagram of the power supply and input/output (I/O) section included in the presently preferred system of the present invention.
30 Figure 11 is a graph showing variation in oxygen saturation as a function of hematocrit.
Figure 12 is a graph of E /E versus Hematocrit.
eaos mo Figures 13A-13B are graphs of E versus Hematocrit at two non-preferred Wavelengths and e~/EZ versus Hematocrit at 35 those non-preferred wavelengths.

. : . , : . . . .. : . . _Figures . 14.A~.1.48. ark :~.g~r.~~hs.._pf E
versus . .. . . : Hematocr. it. . at ~ ..

two non-preferred wavelengths and E~/e2 versus Hematacrit at those non-preferred wavelengths.

.. . . , Figure.. .1.5 ...iilustrat.e.. "verti.ca.7. :.em.itter..
alxgn~ent.
;a~izd .....~

. . . - .:.. the resu3aing non-identical dXb ~ regions ; .. . ... . . . _ .
. . 5 . ~

. . ~- ~..Figure ~ 16 .-illustrates. horizontal. emitter. alignment.

DETAILED~DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present-invention.. is. directed to apparatus and methods for determining biologic~constituent values, such as the hematocrit value, transcutaneously and .

is achieved by passing at least two noninvasively.This ~aavelsng~lis ~ of'~' ~:~ight "onto bf~ '~thxoiigh-~ bbdy -W~idsuesr stitch ~~ as~ ' -the finger, earlobe, or scalp, etc., and then compensating.

for the effects of body tissue and fluid by modifying the Beer-Lambert Law. The_principles within the scope of the present invention may also be utilized to provide a hematocrit-independent oxygen saturation and oxygen content-measurements as well as noninvasive measurement of blood ' constituents such as glucose, cholesterol, bilirubin, creatinine, etc.

Although the present invention will describe in great, detail the transillumination of various body parts, it will be appreciated that reflectance spectrophotometry may alternatively be employed where transillurnination is difficult to accomplish. As used herein, the term "body part" is intended to include skin, earlobe, finger, lip, forehead, etc. Because the principles within the scope of the present invention can be adapted by those skilled in the art for in vitro measurement of hematocrit and other blood constituents, the term "body part" is also intended to include various in vitro blood containers such as tubes and cuvettes.

.. : :.. . . : .1... -. ,,S,~~ectrophotome~ric Methods. , , ~ y ' ' y . . . .
.. ' . ' ' .
Spectrophotometric methods have been described in the prior art which monitor various metabolites in bady fluids.
. , ~, . _ , . . . . : .Radiation,, ....'typica.l.ly.. ..in . the;. visible :.
or. , .near . infrared v 5'~~ ~'regioii; ~ is directedonto' aii " exterior body ~ part ' for transcutaneous.penetration of.the.,radiation. The radiation.
is then monitored reflectively or transmissively by a photodetector or similar sensor: Radiation spectra are chosen at wavelengths where the metabolite or compound sought for either absorbs highly or poorly. Some examples of such spectrophotometric methods ark described in U.S.
Patent No. 4,653,498 for pulse oximetry, U.S. Patent . . No . 4 , 655'; 225 ' ' foW .: 'bloo~d~ =~glwcosew...monitoring ~ ~ ~ and=
more ~ .. , recently U.S. Patent No. 4,805,623 for monitoring various blood metabolites (glucose, cholesterol,-etc.).
A theoretical. basis for the spectrophotometric techniques is the Beer-Lambert Law:
Ioe -Eud ( 1) Equation (1) may also be written:
ln(IjIo) - ~-eXd (la) wherein IQ is the incident intensity of the source radiation, I is the transmitted intensity of the source through the sample, E is the ext:i~ction coefficient of the sought for component, X is the concentration of the sample component in the tissue itself, and d is the optical path length (distance).
The Beer-Lambert Law (1) permits in vitro solute concentration determinations. However, quantitative measurements have not been possible in the body since the scattering of the incident photons passing into and through the integument and subdermal regions is extensive and _ . _9_ " v. highly 'variabl.e. ' . ~Thi.s, scattering .s~po,i~.s the BeerLambert . .
, Law by adding a variable loss of radiation to the measurement and also extends the path length of the ., .. , .... incident,,.photons. .b~ an' unknown amount as well., ' ' S 'Even though opti~calw ~ pulse rate ~monitors~, plethysmographs,.,and pulse oximeters are."known, their-development has been accelerated by techniques which allow for cancellation of the optical scattering effects to a large extent. This development began with U.S. Patent No. 2,706,927 and was further refined by Yoshiya, et. al.
(Med. and Biol. Eng. and Computing, 1980 Vol. 18, Pages. 27-32 ) , Koneshi in U. S. Patent ~ No. 3, 998, 550, and . . .-. . . . . . . . Ramagur~i iv wU.-S ~ -- N~.w-patent-:.;.4.,:2661, 554., ..~whicb ut~i.lized.:..a_ .. . ..
technique of analyzing the resultant opto-electronic signal by dividing it into its AC and DC components. The AC and DC components are mani.'pulated with logarithmic amplifiers in such a way as to eliminate the above-mentioned transdermal optical effects (the variable amount of-radiation loss due to scattering in the tissue and the 2~0 unknown and variable amounts of optical path length increase).
Until now, the AC-DC cancellation techniques have not been successfully adapted for the measurement of hematocrit or hematocrit-independent blood oxygen saturation.
2. Noninvasive Differential-Ratiometric Spectro_pho.tometry ' It is assumed that incident radiation passing onto or into a living tissue will pass through a combination of blood, tissue, and interstitial fluid compartments. The _ -10-. , light ,attenuated .: b~~, such a , living , tissue. ~ can .be .expres.sed ':
by the modified Beer-Lambert equation:
. ... .. . . . . . . ~ z ._ . .Ipe <eb<xetx">+~txta.;xi )a+c _ . . , , . ( 2 ). . . .
Equation .( 2 ) may also be written , . , ln(I/Ip) - -(Eb(Xe+XY)+etXt+Eixi)d+G (2a) Where Eb, Et, and Ei represent the extinction coefficient in the blood, tissue, and interstitial fluid compartments, respectively; Xa and X~ represent the arterial and venous blodd~ :~ _ .C.oncentrationw: (Xb-.Xe+X~j :m .: .. :Xt .,..,.represents -. the :.
concentration of the tissue absorbers, and Xi represents the relative concentration of water and dissolved components in the interstitial fluid compartment; d represents the intrasensor spacing; and G is a constant of the geometric -~
configuration.
As the blood layer pulsates, the concentration terms change. The term d can be fixed by the geometric configuration of the device., Taking the partial derivatives of equation (2) with respect to time and dividing by equation (2) gives:
aI/at =~E~(axa/at+ax~/at) + EtaXt/at + E;ax;/at~d +aG/at ( 3 ) which can be simplified at each compartment and wavelength by letting X' =ax/at, and G' =aG/<'3t, and V~=-(c3IIc3t' to give Jx V~ _~Eb(Xa+Xv~ + EtX C + E iXild +G/ (,4 ) Assuming that Xt and G do not vary significantly over the pulse time interval, then G'=0 and X't=0, and equation (4) can be simplified to , CA 02449621 2003-12-09 . _11-. , . , . . .. ~.. ~Z-(.Eb~Xa+Xv~ *,E;~;~a: . . ,: . ..' . .. _ .. ~, ,,' :( ~:. .
. ~ Exami~ing....the vtranspovtwb~etween. X8... and....~~~. ~"~~ -~ca~i-:..farm~.a..: - .
proportionality constant I~ such that, ~ X'.~ -~,X' a, representing the reactionary nature of the venous component, and further reduce the above equation to Vz =(Eb~l_Kv~Xa + E iXi)d ( 6 ) Since X' a and X' i ' are not wavelength (~l) wdependent, V' ~
. . value. . :a~.. .. dif.f~.rent. wavelengths can , be....dif ferentially, .
subtracted to produce a hematocrit independent term which contains only EiX'i information. Although the term V~ sos/V~ ~sio Provides- useful information regarding relative . changes in hematocrit, it should be recognized that the simple V' ~s/V' ~3~o ratio is not sufficiently accurate for hematocrit value determination unless the EiX'i term is known or eliminated. For example, the EiX' i8os term can be neglected since ei~s is extremely small, whereas the EiX' ;310 term is about 25%-50% of the Eb~3~~ value of blood itself and cannot, therefore, be neglected without affecting accuracy:
Figures 3 and 12 suggest that a linear combination of V° z at ~=805 nm and a=970 nm will have a near constant value .for a range of Hct values. Since the extinction coef f icients E iaos and E i97o are well known, or can be empirically determined, a precise proportionality constant R~ can be found to produce i_ i i Ei970Xi -V970~R1V80s ( ) This correction term can now be applied with a second proportionality constant R2 (whe:re RZ is approximately equal . -1.2-. to . E i f3t~°~ i970)...: t~ -~~e y'~.~3~0 . termvto: exactly. remove its.,. E.;y3lox~..;.. .., . .....
sensitivity, hence: ' r r _ r _ m g . . ' ' y. , . ~ . Eb1310~f -K.r,Xa.' V13'10 R2(VSt70 R1~805~.; ...:. . . .. ( ) ' ... , , .; . .... . .. . .., . .. :,. . .. , . , : . : . , _ . . . .. ,. .,::
.. .
,. . .. . ,.,.. ' ..
This corrected' term 'can now "be 'used ' ratiometrically with V' $0s to remove the ( 1-ICY) X' 8 ', and leave the pure extinction coefficient ratio represented by Equation, (9) below and shown graphically in Figure 4.
r E aaos __ Vaos ~b1310 / _ ( ~~ _ I
V 1310 2 970 , . . . BOS
.. .... . : . . . . ....... . .... .,. ,. .. . .,. . . ... .. .. ., . .....,..
. .. . .. . . . ., . ... : . . . V .. .. . .. . . . . ...... .. . ~. ... . ...
. ., . . .
.,. R.'V R1 It should be noticed that the following assumptions to and requirements are essential in hematocrit determinations (but in the case of pulse oximetry these requirements may not be of the same degree of significance).
A. Even though wavelengths ~1=805 nm and ~1=1310 nm - are near isobestic, the actual function of E versus Hematocrit at each given wavelength must hold hematocrit information that is different in curvature, or offset, or linearity, or sign from the other. See Figure 3. If the functions Ea versus hematocr3.t are not sufficiently different, then the ratio Eb~1/Eb~z will not hold hematocrit ~.nformation. See Figures 13A and 13B and Figures 14A
and 14B. Even though the foregoing discussion refers to the isobestic wavelengths of Jl=805 nm and A=1310 nm, it will be appreciated that other isobestic wavelengths, such as ~=570 nm, .1=589 nm, and JL=155() nm, may also be utilized.
B. Further, the wavelengths should be selected close enough to one another such that the optical path lengths, d, are approximately the same. Longer wavelengths are preferred since they exhibit less sensitivity to scattering, s:

s« 2 (10) C. The, geometric. or , spat ial relationship of the.

. . . . . . . 'emitters ~ and ~ ~seiisorsv ~~'ls ... . im~or~.ai~t : " Fo"r , .. . ' "iiistar~c~~; -'... vif..:~ . _ ..

vertically aligned vemitters axe used in an earlobe-measuring device, then~the top=most emitter may illuminate a different amount of blood filled tissue than the lower emitter. If only one sensor is used, then there will be a disparity between X'b at each wavelength. See Figure 15, wherein Xb> > X~ > X~. Furthermore, the sensor-emitter spatial separation distance is very important because the , pressure _ ;applied ., to ..the, tissue between , the sensor ,. and . , , .

arteriolar and capillary vessel the emitters affects compliance. This changes the X' as the pressure {or distance) changes. This change in X' then modulates the V' a function. Therefore, the sensor-emitter separation distance must be such that the pressure applied to the earlobe, fingertip, or other body member, does not affect function. This sensor separation distance is the V' ~

empirically determined and should generate less than 40 mm .- Hg applied transmural pressure.

A horizontal alignment (Figure 15) of the emitters with respect to the single sensor can be arranged so that the emitters and sensors illuminate and detect identical regions of aX~~ and aX~2. It is important to note that the term d, the sensor-emitter separation, will be different between ~,~ and 7lz by the cosine of the angle between the sensor and emitter. Therefore, if any misalignment from normal occurs, the term d will not cancel to obtain equation {9).

The preferred arrangement is wherein all the emitters (660, 805, 950, and 1310 nm) are located on the same substrate. This is~ preferred because the emitters will then illuminate essentially the same Xb region.

D. In the case of reflectance spectropho-tometry, an, ag~rture for the sensor and each emitter is required. See Figure 1B. Also, a sensor-emitter separation is required y y . so that ,he reflectance of the .first .layer. o~f wtissue, Rt, ~ y(a: ' ..
non-blood layer of epithelium) does. not further exaggerate a multiple scattering effect, i.e. the total reflectance, R, measured would contain spurious information of the epithelial layers' reflectance as well, where:
2~
R=Rt+ Tt Rb (11) t1 _ Rb~ Rt) 1'0 c~there R "is the total retiectawce, Rt is the reflectancewdue . .
to the first tissue-epithelial layer, Rb is the reflectance due to the blood layer, and Tt is the transmission through the first tissue layer'.
The reflectance equations describing Rt or Rb must now l~ sum all of the backscattered light that the sensor detects, i.e.,:
Rb=~~~(source function)~(scattering function) (12) While equation (9) describes the theory of the noninvasive hematocrit device, the four' assumptions (A-D) 20 are important to the repeatability and accurate functioning of the hematocrit device.
Assuming items A throutgh D are dealt with appropriately, then (9) becomes:
Ebxt _ (st +'_~t~ ( 13 ) Ebd2 ' ~SZ ~~ k2, where s is a scattering constant and k ~.s an absorption constant, and where in whole blood:
~. , . . ~ ~ ~S - 'y ffSHct (~l-Hct) .., . ' ~ ;~ ~.;;: .. ,.~ ~~ ~f~14 ), ,.
k = vaHct ( at isobestic wavelengths ) ( 15 where vs is the scattering cross section and va is the absorption cross section.
l0 From the foregoing, E, the extinction coefficient, is not a simple function of the absorption coefficient, k, normally determined in pure solutions. Rather, it contains a diffusion or scattering term, s, which must be accounted for in a non-pure solution media such as whole blood and . tissue.
Finally, substituting (14) and (15) into (13):.
E~1 _ Qs1(1-Hct) +Qat (16) ._ E.12 Qs2 ( 1-HCt) + Qa2 Therefore, the ratio e~'/e~2 is a function of hematocrit. From Figure 4, a look up table or polynomial curve fit equation may be obtained and utilized in the final displayed hematocrit results. Knowing the actual hematocrit value, it is straightforward to see (Figure 2) that a wavelength at 660 nanometers can be~ selected to obtain an E ratio wherein the hematocrit-independent oxygen saturation value is derived. For example, equation (16) would become:
Ego _ Qs~o ( 1' Hct) + aabbo + Sa02 ( Qao~o - Qa~s~oj E ~ Q (1-Hct +a +S 0 a -a (17) bB05 s805 ) a805 a 2 ( ao805 as805~
Equation (17) shows both the hematocrit and oxygen saturation dependence on each other.

-ls-,Figure 11 graphically demonstrates the need for a hematocrit-independent blood saturation device. As either the hematocrit value or percent oxygen saturation decreas~es,~ the ypercent . . saturation ~ ~y error ~~ .becomes.. ...
unacceptable for clinical usage. For examgle, it is not uncommon to see patients with a low hematocrit (about 20%) who.have respiratory embarrassment (low oxygen saturation) as well. Hence, the clinician simply requires more accurate oxygen saturation values.
to Knowing the hematocrit and oxygen saturation values, the computation of the Oxygen Content ~s trivial and maybe displayed directly (a value heretofore unavailable to the clinician as a continuous, real-time, noninvasive result):
[ Oxygen Content ] - ;Hct ~ SaO~ ~ K ( 18 ) where K is an empirically determined constant.
Referring to the equations (16) and (9) a decision must be made by the computer as to the suitability of utilizing the Taylor expansion approximation to the logarithm. This algorithm is maintained in the software as a qualifying decision for the averaging and readout algorithms. The Taylor approximation is only valid for small aI/r~t values.

3. Nonpulsatile Applications ' a. Valsalva's Maneuver to Simulate Pulsatile Case It is interesting to see the similarities between this AC pulsatile derivation and an analogous DC technique. By taking the logarithm of two intensity ratios, values of Eb 3o and e~ can be obtained from the modified Beer-Lambert equation (equation (2a)). These same extinction coefficients can be manipulated by the identical proportionality constants R~ and Rz found previously to exactly eliminate E;~3~oX; and yield . '17-E bao5 '_ UaoS ( 19 ) Eb1310 ~ U1310 R2 ~rJ9T0'~ R1U805~ .
I
Where the term ' ' ~ ~ Ua= In ~ 2 .
I1 ~k represents v the l'ogarithm' ~ of intensity ratios at Xb values of X1 and Xz.
It should also be noted that the two derivations (AC
and DC) fold into' one another through the power series expansion of the ln(1+Z) function:
Z2 .Z3 ln(1+z) =z- +s-... (20) When the.value DI=Iz-It, it can be seen that 1nC Iyl = 1nC ~ 1I11 = 1n(1+ ~~ _ ~ + High Order Terms ( 21) which means that for small changes in Xb, the AC (partial_ derivative) and DC (logarithmic) derivations are similar _ and can each be precisely compensated through this differential-ratiometric . technique to provide an noninvasive e~os/eb~3lfl ratio which is independent of both the constant and time-varying tissue and interstitial fluid' terms.
One currently preferred method of obtaining the two intensity ratios is to have the patient perform Valsalva's maneuver. Valsalva's maneuver is an attempt to forcibly exhale with the glottis, nose, and mouth closed. This maneuver increases intrathoracic pressure, slows the pulse, decreases return of blood to the heart, and increases venous pressure. Obtaining intensity measurements before and during Valsalva's maneuver provide sufficiently different intensity ratios to utilize equatian (19). Even a deep breath can be enough to obtain sufficiently different intensity ratios.

_ . _18.
b. Stepper Motor Technicrue Another technique to simulate pulsatile blood flow arid to eliminate the skin's optical scattering effects, while a-t~ the same time preserving -the blood~~borne .hematocrit and oxygen saturation information, is described below. By utilizing a stepper motor 9 in the earlobe clip assembly l0 on an earlobe 11 of a patient such as that illustrated in Figures 5, 6A, 15, and 16, one can produce a variation of Xb sufficient to utilize equation 19. The stepper motor 9 could even produce a bloodless (Xe 0) state, if required.
However, equation 19 shows that only a' difference between Xb~ and Xb2 is needed.
The major advantage of this technique is that under clinical conditions of poor blood flow, poor blood pressure, or peripheral. vascular disease, where pulse wave forms are of poor quality for the (c3I/c?t)/I technique, this DC stepper motor technique could be utilized.
c.. Oxvcren Saturation Determination The above techniques describe conditions and equations wherein isobestic wavelengths are chosen such that the hematocrit value abtained has no interference from oxygen saturation, hence an independently determined hematocrit value.
One, however, may choose k2 (the reference wavelength) in equation (13) at 1550 nm as well. In the radiation legion 900 to 2000 nm the blood absorption coefficients depend on hematocrit and water, whereas at 805 nm the blood absorption coefficient only depends on hematocrit.
Therefore, utilizing in combination, wavelengths of 660, 805, and 1550 will also give a technique to determine hematocrit (~$os/E~sso) and oxygen saturation (~~o/e8os)' These 3 wavelengths are particularly important since 660, 805, and 1550 nm (or 1310 nm) are readily available LEDs, such-as, respectively, MLED76-Motorola, HLP30RGB
Hitachi, and ETX1550-EPITAXX (or NDL5300-NEC), with the benefits of low cost and low optical power (reducing any question of possible eye damage).

The manufacturing of a multi-chip LED emitter becomes reasonable, cost-wise, and provides increased accuracy since the LED sources have practically no separation distances and appear as a single point source, This invention may be applied to th.e determination of other components (included, but not limited to, glucose, or cholesterol) in any range of the electromagnetic spectrum in_which spectrophotometric techniques can be utilized.

4. Currently Preferred Apparatus -An earlobe clip assembly 10 as in Figures 6, 6A, 15, and 16 (with or without the stepper motor 9 shown in Figure 6A) a finger clip assembly 6 used on a finger 7 as shown in Figures 1, 1A, and 1B are two currently preferred embodiments for practicing the present invention. The photodiodes 3 and emitters 1 and 2 in each are placed in accordance with appropriate alignment. -Consider first the sensor technology in the transmissive mode of operation. An earlobe or fingertip housing can be provided with discreet emitters and two photodiode chips (of different sensitivity ranges, 600-1000 nm and 1000-1700 nm ranges] placed on one substrate, such as a TO-5 can (Hamamatsu K1713-03j. The emitters likewise can be two or more emitter chips (i.e., ~1 = 805, '1310, 660, and 950 nm) placed on a common substrate and illuminated through a TO-39 can.

Finally, a single substrate multi-wavelength emitter and a multi-wavelength detector, assembled in one. small physical housing for each, make alignment and detection sensitivity more repeatable, and hence more accurate.

The preferred emitter chips would have wavelengths, for hematocrit-only measurements, at 805 nm, 950 nm,. and 1310 nm (or 805 nm, 950 nm, and 1550 nm). Although in theory, an emitter having a wavelength of 970 nanometers, rat~:er than .950 nm, would provide more accurate information, 970 nm emitters are not presently available commercially. These wavelengths are currently preferred y because of the different curvature and baseline offset of the E versus Hematocrit at those wavelengths. See Figure 3. Hence, the hematocrit information will exist in the ratio e~~/E~2. See Figure 4.
Furthermore, the choice of 805 nm and 1310 nm (or 1550 nm) rather than 570 nm and 805 nm is because there is no water absorption in the 570 nm (or 589 nm) and 805 nm isobestic wavelengths. However, there is tremendous water absorption at 1310 nm and 1550 :nm. Hence, the ratio of 570 nm to 805 nm, as a reference, would not yield hematocrit information because.there would be no offset due to water in the plasma. See Figures _13A and 13B and Figures 14A and 14B. _ If hematocrit-independent oxygen saturation is desired then the emitter chip wavelengths would be 660 nm, 805 nm,w 950 nm, and 1310 nm (or 1550 nra) (the 660 nm is MLED76, Motorola or ~ TOLD 9200, Toshiba). Likewise, the photodetector single substrate could house at least two chips, such as a Hamamatsu K1713--03.
It will be appreciated that those skilled. in the art would be able to add other chips to the single substrate at wavelengths sensitive to other metabolites (glucose, cholesterol, etc.). The above mentioned emitter and detector connections can be seen in the analog schematic diagram illustrated in Figures 7 and 9B-9D.
The sensor technology in the reflectance mode must conform to two embodiment parameters. See Figure 1B. The diameter and thickness of the aperture 8 in which figure 7 is received in combination with the sensor-emitter separation distance are important to provide a detection region within the subdermis 1:? at points a and b of Figure 1B, where the radiation impinges on blood-tissue without the multiple scattering effects of th;e epithelial layer, Rt. The determination of optimum sensor 3 separation and aperture 8 sizeswis done empirically' from numerous fingers 8 with varying callous and fingernails 13. Minimum sensor separation and aperture diameters can be established wherein Rt, of equation (14) is eliminated.

Figures 7, 8A-8C, 9A=9D, and l0A-lOB detail .the electronics of one circuit suitable for use within the scope of the present invention. The memory and computation means (Figures 8A-8C) are connected via a 'bus" structure between PROMS (U110,U111), microprocessor MC68HC000 (U106), static RAMS (U112,U113), and isolation buffers to the low-level analog circuitry (Figure 7). A crystal controlled oscillator circuit (UlOIA,B) is divided by 2 to provides a symmetric master clock to the microprocessors this clock is further subdivided~and used to provide clocking for the r analog-to-digital converter (U208) and timer (U109).-Strobe lines are generated through a decoder arrangement to-drive each of the subsystems of 'the device and also control the isolation bus buffers (U201,U202).

Timer outputs are fed back into the microprocessor and encoded (U104) to produce interrupts at specific intervals for system functions. One timer is shared by subsystems which control the liquid crystal display means, the keyboard entry means, the audible indicator, and the Cycling background system self-test. Another timer is dedicated exclusively to provide a high priority interrupt to the microprocessor; this interrupt drives software which controls the basic sensor sampling mechanism. An expansion connector (J101) is included to allow extended testing of the device or connection to external data-logging equipment such as a printer or computer interface.

The local bus isolates the sensitive analog circuitry from the main digital circuitry. Th~,s prevents spurious crosstalk from digital signals into the analog circuitry and thereby reduces superimposed noise on the measured signals. It is on this local bus that the Digital-to Analog Converters (DAC) and Analog-to-Digital Convertors (ADC) transmit and receive digital information while' processing the low-level analog signals.
The Low Level Sensor electronic section, Figure 7, combines subsystems to both measure and.modulate the current produced from each optical sensor. Since the pulsatile component of the optical energy transmitted through or reflected off of tissue, comprises only a small part of the overall optical energy incident on the sensor,.
means are provided to '°null out" in a carefully controlled and accurately known way the non-pulsatile component of the light-produced current in the sensing detector. The remaining signal can then be dc-amplified and filtered in a straightforward manner and prs~sented to the ADC (U208) for conversion into a digital value representative of the relative AC pulsatile component. Furthermore, because the.-relationship between the pulling current and the average value of this AC component is known; the DC component can easily be caicuiated as a 'function of the sensing means' sensitivities and the electronic stages' gains': The functions determining these AC and DC values can (if~
necessary) be trimmed in software by calibration constants which are stored in EEPROM (U307) and retrieved each time the unit is powered on.
The current which modulates the optical sources (LEDs or Laser Diodes) is also controlled (U203) and precisely adjusted (U306) to optimize signal reception arid detection.
~ Through software control, the modulation current can be adjusted on a pulse-by-pulse basis to minimize nvise-induced inaccuracies. Furthermore, by sampling the sensors with the modulation sources disabled appropriately, background noise (such as 60 Hz) can be rejected digitally ~ 35 as common-mode noise. Thus, by controlling the optical -2~3-source energy and modulating the nulling current in the photosensor circuitry, it is possible to effectively cancel the effects of ambient radiation levels and accurately measure both the static (DC) and time-varying (AC)

5, components of transmitted or reflected light.
Interrupt-driven software algorithms acquire the . sensor data, provide a real-time pulse wave contour, and determine pulse boundaries. Completed buffers (i.e. one entire pulse per buffer) of sensor data are then passed to the foreground software processes for computation. This involves the determination of~the background-compensated AC
pulsatile and DC static values of intensities for each wavelength. Through averaging and selective elimination of abnormal values, results are then calculated using equation (9) and displayed on the LCD. The modulating and pulling currents are .(if necessary) also adjusted to utilize the electronic hardware efficiently and optimally.
5. Summary Although the foregoing discussion has related to noninvasive analysis of blood hematocrit information, it will be appreciated that the above-mentioned emitters, sensors, and circuitry may be adapted for invasive in vitro analysis of blood hematocrit values. The principles within the scope of the present invention which,compensate for spatial, geometric, and tissue variations may be used to compensate for similar variations in an in vitro blood container. Such a device would allow hematocrit values to be determined-rapidly and accurately.
Those skilled in the art will also appreciate.that the methods within the scope of the present invention for determining blood hematocrit values may be adapted for determining non-hematocrit biologic constituent values such as glucose, cholesterol, etc. To determine biologic constituent information, the effects of competing blood, tissue, and interstitial fluid constituents must be eliminated. It is believed that these. effects may be eliminated by appropriate modification of the differential ratiometric techniques described above.
It is important to recognize that the present invention is not directed to determining the tissue hematocrit value. The tissue hematocrit value, in contrast with the blood hematocrit value, reflects the amount of red blood cells in a given volume of tissue (blood, interstitial fluids, fat, hair follicles, etc.). The present invention is capable of determining actual i:ntravascular blood hematocrit and hemog~5.obin values.
From the foregoing, it will be appreciated that the present invention provides a system and method for noninvasively and quantitatively determining a subject's hematocrit or other blood constituent vale. The present invention determines the hematocrit noninvasively by utilizing electromagnetic radiation as the transcutaneous information carrier. Importantly, the present inventionw-may be used on various body parts to provide accurate quantitative hematocrit values.
It will also be appreciated that the present invention also provides a system and method which can provide immediate and continuous hematocrit information for a subject. The present invention further provides a system and method for noninvasively determining a subjects's blood oxygen saturation (S802) independent of the subject's hematocrit. In addition, the present invention provides a system and method for noninvasively determining a subject's hematocrit and/or blood oxygen saturation even under conditions of low blood perfusion.
The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appende3 ,claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

Claims (47)

CLAIMS:

1. A method for noninvasively determining hematocrit as a biological constituent value of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part or the extracorporeal passageway defining a blood conduit, the method comprising the steps of:
selecting a first radiation wavelength;
selecting a second radiation wavelength which exhibits a greater absorption coefficient to water than said first radiation wavelength;
directing said first and second radiation wavelengths into the blood conduit;
detecting the amount of first radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic that constitutes one of a first curvature, first offset, first linearity, or a first sign;
detecting the amount of second radiation after passing through the blood conduit, said detected amount of second radiation having at least one extinction characteristic that constitutes one of a second curvature, second offset, second linearity or a second sign and said characteristic in said detected amount of first radiation being different from the corresponding characteristic in the detected amount of second radiation;
and mathematically manipulating the detected amount of first and second radiation wavelengths with a polynomial function to determine the hematocrit value, wherein said hematocrit value is determined without knowing blood volume.

2. The method of claim 1, wherein said manipulating step comprises forming the ratio of the .DELTA.i/i ratios for each of the first and second radiation wavelengths multiplied by the ratio of the log (I/I0) for each of said first and second radiation wavelengths.

3. A system for determining hematocrit as a first biological constituent value of the blood of a patient, the blood having a second biological constituent competing with said hematocrit and flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part or the extracorporeal passageway defining a blood conduit, the system comprising:
blood conduit receiving means for receiving the blood conduit containing the flowing blood of the patient;
a first emitter positioned on said conduit receiving means for emitting a first radiation wavelength;
a second emitter positioned on said conduit receiving means for emitting a second radiation wavelength which exhibits a greater absorption coefficient to water than said first radiation wavelength;
directing means for directing said first and second radiation wavelengths into the blood conduit;

first detecting means for detecting the amount of first radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic that constitutes one of a first curvature, first offset, first linearity, or a first sign;
second detecting means for detecting the amount of second radiation after passing through the blood conduit, said detected amount of second radiation having at least one extinction characteristic that constitutes one of a second curvature, second offset, second linearity or a second sign and said characteristic in said detected amount of first radiation being different from the corresponding characteristic in the detected amount of second radiation; and means for comparing the detected amount of first and second radiations to determine the hematocrit value, wherein said hematocrit value is determined without knowing blood volume.

4. The system of claim 3, wherein said first and second wavelengths are at or near the isobestic points of reduced hemoglobin and oxyhemoglobin.

5. The system of claim 3, wherein said first curvature is different from said second curvature.

6. The system of claim 3, wherein said first offset is different from said second offset.

7. The system of claim 3, wherein said first linearity is different from said second linearity.

8. The system of claim 3, wherein said first sign is different from said second sign.

9. The system of claim 3, wherein said first and second photodetecting means constitute a single photodetector.

10. The system of claim 3, further comprising:

a third emitter positioned on said conduit receiving means for emitting a third radiation wavelength;

second directing means for directing radiation having the third wavelength into the blood conduit;

detecting means for detecting the amount of radiation having the third wavelength which is extinguished by the blood in the blood conduit;

means for operating on the amount of detected radiation having the first, second and third wavelengths such that the spatial, geometric, and tissue variations are eliminated in each radiation wavelength; and means for operating on the amount of detected radiation having first, second, and third wavelengths to compensate for the effect of the second biologic constituent.

11. A system for determining a first biological constituent value of the blood of a patient, the blood having a second biological constituent different from said first biological constituent and flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part or the extracorporeal passageway defining a blood conduit, the system comprising:

blood conduit receiving means for receiving the blood conduit containing the flowing blood of the patient;

a first emitter means positioned on said conduit receiving means for emitting a first radiation wavelength;

a second emitter means positioned on said conduit receiving means for emitting a second radiation wavelength which exhibits a greater absorption coefficient to water than said first radiation wavelength;

directing means for directing said first and second radiation wavelengths into the blood conduit;

first detecting means for detecting the amount of first radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic;

second detecting means for detecting the amount of second radiation after passing through the blood conduit, said detected amount of second radiation having at least one extinction characteristic, said characteristic in said detected amount of first radiation being different from the corresponding characteristic in the detected amount of second radiation;

means for applying a representation of the extinction coefficient in a ratiometric polynomial where the polynomial is related to a change in a physical parameter; and means for solving the polynomial to determine the first biological constituent without knowing blood volume.

12. The system of claim 11, wherein said first, and second emitter means are a predetermined distance from each other.

13. The system of claim 11, wherein said first emitter means comprises two emitters.

14. The system of claim 13, wherein said second emitter means comprises two emitters.

15. The system of claim 14, wherein said first and second emitter pairs are spaced from each other.

16. The system of claim 11, wherein said first biologic constituent is hematocrit.

17. The system of claim 11, wherein said first biologic constituent is hemoglobin.

18. The system of claim 11, wherein said first biologic constituent is glucose.

19. A system for determining hematocrit as a biological constituent value of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part or the extracorporeal passageway defining a blood conduit, the system comprising:

blood conduit receiving means for receiving the blood conduit containing the flowing blood of the patient;

a first emitter positioned on said conduit receiving means for emitting a first radiation wavelength;

a second emitter positioned on said conduit receiving means for emitting a second radiation wavelength which exhibits a greater absorption coefficient to water than said first radiation wavelength;

directing means for directing said first and second radiation wavelengths into the blood conduit;

first detecting means for detecting the amount of first radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic that constitutes one of a first curvature, first offset, first linearity, or a first sign;

second detecting means for detecting the amount of second radiation after passing through the blood conduit, said detected amount of second radiation having at least one extinction characteristic that constitutes one of a second curvature, second offset, second linearity or a second sign and said characteristic in said detected amount of first radiation being different from the corresponding characteristic in the detected amount of second radiation; and means for mathematically manipulating the detected amount of first and second radiation wavelengths with a polynomial function to determine the hematocrit value, wherein said hematocrit value is determined without knowing blood volume.

20. The system of claim 19, wherein the polynomial is the ratio of the .DELTA.i/i ratios for each of said first and second radiation wavelengths multiplied by the ratio of the log (I/I0) for each of said first and second radiation wavelengths.

21. A system for determining biological constituent value of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part or the extracorporeal passageway defining a blood conduit and the system comprising:

blood conduit receiving means for receiving the blood conduit containing the flowing blood of the patient;

a first emitter means positioned on said conduit receiving means for emitting a first radiation wavelength;

a second emitter means positioned on said conduit receiving means for emitting a second radiation wavelength which exhibits a greater absorption coefficient to water than said first radiation wavelength;

directing means for directing said first and second radiation wavelengths into the blood conduit;

first detecting means for detecting the amount of first radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic exhibiting functional information in the form of one of a first curvature, first offset, first linearity, or a first sign;

second detecting means for detecting the amount of second radiation after passing through the blood conduit, said detected amount of second radiation having at least one extinction characteristic exhibiting functional information in the form of one of a second curvature, second offset, second linearity, or a second sign and said information in said detected amount of first radiation being different from the corresponding information in the detected amount of second radiation; and means for mathematicall manipulating the detected quantities of the first and second radiation wavelengths with a polynomial function to determine the value of a biological constituent, wherein said biologic constituent value is determined without knowing the blood volume.

22. The system of claim 21, wherein said first emitter means comprises two emitters.

23. The system of claim 22, wherein said second emitter means comprises two emitters.

24. The system of claim 22, wherein said first and second emitter pairs are spaced from each other.

25. The system of claim 21, wherein said biologic constituent is hematocrit.

26. The system of claim 21, wherein said biologic constituent is hemoglobin.

27. The system of claim 21, wherein said biologic constituent is glucose.

28. A system for determining a first biological constituent value of the blood of a patient, the blood having a second biological constituent different from said first biological constituent and flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part or the extracorporeal passageway defining a blood conduit, the system comprising:
blood conduit receiving means for receiving the blood conduit containing the flowing blood of the patient;

a first emitter means positioned on said conduit receiving means for emitting a first radiation wavelength;

a second emitter means positioned on said conduit receiving means for emitting a second radiation wavelength which exhibits a greater absorption coefficient to water than said first radiation wavelength;

directing means for directing said first and second radiation wavelengths into the blood conduit;

first detecting means for detecting the amount of first radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic;

second detecting means for detecting the amount of second radiation after passing through the blood conduit, said detected amount of second radiation having at least one extinction characteristic, said characteristic in said detected amount of first radiation being different from the corresponding characteristic in the detected amount of second radiation;

means for forming for each wavelength the ratio of a change in a physical parameter over time to the value of the physical parameter; and means for mathematically manipulating the formed ratio with a polynomial function, wherein the value of the first biological constituent is determined without knowing blood volume.

29. The system of claim 28, wherein the parameter is light intensity.

30. The system of claim 28, wherein the parameter is distance.

31. The system of claim 28, wherein the parameter is time.

32. A system for determining a first biological constituent value of the blood of a patient, the blood having a second biological constituent different from said first biological constituent and flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part or the extracorporeal passageway defining a blood conduit, the system comprising:

blood conduit receiving means for receiving the blood conduit containing the flowing blood of the patient;

a first emitter means positioned on said conduit receiving means for emitting a first radiation wavelength;

a second emitter means positioned on said conduit receiving means for emitting a second radiation wavelength which exhibits a greater absorption coefficient to water than said first radiation wavelength;

directing means for directing said first and second radiation wavelengths into the blood conduit;

first detecting means for detecting the amount of first radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic;

second detecting means for detecting the amount of second radiation after passing through the blood conduit, said detected amount of second radiation having at least one extinction characteristic, said characteristic in said detected amount of first radiation being different from the corresponding characteristic in the detected amount of second radiation;

means for forming for each wavelength a ratio of a change in transmitted intensity over time to the transmitted intensity;

means for differentially subtracting the formed ratio at the first wavelength from the formed ratio at the second wavelength; and means for mathematically manipulating the differentially subtracted ratio with a polynomial function, wherein the value of the first biological constituent is determined without knowing blood volume.

33. A method for noninvasively determining hematocrit as a first biological constituent value of the blood of a patient, the blood having a second biological constituent competing with said hematocrit and flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part or the extracorporeal passageway defining a blood conduit, the method comprising the steps of:

selecting a first radiation wavelength;

selecting a second radiation wavelength which exhibits a greater absorption coefficient to water than said first radiation wavelength;

directing said first and second radiation wavelengths into the blood conduit;

detecting the amount of first radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic that constitutes one of a first curvature, first offset, first linearity, or a first sign;

detecting the amount of second radiation after passing through the blood conduit, said detected amount of first radiation having at least one extinction characteristic that constitutes one of a second curvature, second offset, second linearity or a second sign and said characteristic in said detected amount of first radiation being different from the corresponding characteristic in the detected amount of second radiation; and comparing the detected amount of first and second radiations to determine the hematocrit value, wherein said hematocrit value is determined without knowing blood volume.

34. The method of claim 33, further comprising the steps of selecting the first and second wavelengths at the isobestic points of reduced hemoglobin and oxyhemoglobin.

35. The method of claim 33, wherein said first curvature is different from said second curvature.

36. The method of claim 33, wherein said first offset is different from said second offset.

37. The method of claim 33, wherein said first linearity is different from said second linearity.

38. The method of claim 33, wherein said first sign is different from said second sign.

39. The method of claim 33, further comprising the steps of:

selecting a third radiation wavelength;

directing radiation having the third wavelength into the blood conduit;
determining the amount of radiation having the third wavelength which is extinguished by the blood conduit;

operating on the amount of detected radiation having the first, second and third wavelengths such that the spatial, geometric, and tissue variations are eliminated in each radiation wavelength; and operating on the amount of detected radiation having first, second, and third wavelengths to compensate for the effect of the second biologic constituent.

40. A method for determining the hematocrit of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part and the extracorporeal passageway defining a blood conduit, the method comprising the steps of:

selecting a first radiation wavelength that is isobestic for Hb and HbO2 and not extinguished by non-hemoglobin components of the blood:

selecting a second radiation wavelength that is isobestic for Hb and HbO2 and extinguished by non-hemoglobin components of the blood:

directing the first radiation wavelength into the blood conduit;

directing the second radiation wavelength into the blood conduit;
detecting the amount of the steady state component of the first wavelength extinguished after passing through the blood conduit;
detecting the amount of the steady state component of the second wavelength extinguished after passing through the blood conduit;

detecting the amount of the pulsatile component of the first wavelength;

detecting the amount of the pulsatile component of the second wavelength;

determining the ratio of the pulsatile component of the first wavelength to the steady state component of the first wavelength;
determining the ratio of the pulsatile component of the second wavelength to the steady state component of the second wavelength;
obtaining a mean value for the ratio of the pulsatile component of the first wavelength to the steady state component of the first wavelength over time;

obtaining a mean value for the ratio of the pulsatile component of the second wavelength to the steady state component of the second wavelength over a period of time; and determining the hematocrit by the ratio of the of the mean values obtained for the first and second wavelengths.

41. The method for determining the hematocrit of the blood of a patient of claim 40, further comprising the step of:
displaying the hematocrit,

42. The method for determining the hematocrit of the blood of a patient of claim 40, further comprising the steps of:

selecting a third radiation wavelength:

directing the third radiation wavelength into the blood conduit;
determining a mean value for the ratio of the pulsatile component of the third wavelength to the steady state component of the third wavelength over a period of time; and calculating the corrected hernatocrit value using a linear combination of the first, second and third wavelengths and their ratios.

43. The method for determining the hematocrit of the blood of a patient of claim 42, further comprising the step of:

display the corrected hematocrit,

44. A system for determining the hematocrit of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient or in an extracorporeal passageway in communication with the circulatory system of the patient so as to be subjectable to transcutaneous examination in the body part or to noninvasive examination in the extracorporeal passageway, the body part and the extracorporeal passageway defining a blood conduit, the system comprising:

blood conduit receiving means for receiving a blood conduit containing the flowing blood of the patient;

a first emitter positioned on said conduit receiving means for emitting a first radiation wavelength that is isobestic for Hb and HbO2 and not extinguished by non-hemoglobin components of the blood;

a second emitter positioned on said conduit receiving means for emitting a second radiation wavelength that is isobestic for Hb and HbO2 and extinguished by non-hemoglobin components of the blood;

means for directing the first radiation wavelength info the blood conduit;

means for directing the second radiation wavelength into the blood conduit;

means for detecting the amount of the steady state component of the first wavelength extinguished after passing through the blood conduit;
means for detecting the amount of the steady state component of the second wavelength extinguished after passing through the blood conduit;

means for detecting the amount of the pulsatile component of the first wavelength;

means for detecting the amount of the pulsatile component of the second wavelength;

means for determining the ratio of the pulsatile component of the first wavelength to the steady state component of the first wavelength;

means for determining the ratio of the pulsatile component of the second wavelength to the steady state component of the second wavelength;

means for obtaining a mean value for the ratio of the pulsatile component of the first wavelength to the steady state component of the first wavelength over a period of time;

means for obtaining a mean value for the ratio of the pulsatile component of the second wavelength to the steady state component of the second wavelength over time; and means for determining the hematocrit by the ratio of the of the mean values obtained for the first and second wavelengths.

45. The system for determining the hematocrit of the blood of a patient of claim 44, further comprising:

means for displaying the hematocrit.

46. The system for determining the hematocrit of the blood of a patient of claim 44, further comprising:

a third emitter positioned on said conduit receiving means for emitting a third radiation wavelength;

means for directing the third radiation wavelength into the blood conduit;

means for determining a mean value for the ratio of the pulsatile component of the third wavelength to the steady state component of the third wavelength over time; and means for calculating the corrected hematocrit value using a linear combination of the first, second and third wave and their ratios.

47. The system for determining the hematocrit of the blood of a patient of claim 46, further comprising:

means for displaying the corrected hematocrit.