WO2003029785A1

WO2003029785A1 - Inline blood viscometer for continually monitoring the circulating blood of a living being

Info

Publication number: WO2003029785A1
Application number: PCT/US2002/030504
Authority: WO
Inventors: Kenneth Kensey; William N. Hogenauer; Young I. Cho; Sangho Kim
Original assignee: Rheologics, Inc.
Priority date: 2001-09-28
Filing date: 2002-09-25
Publication date: 2003-04-10

Abstract

An inline blood viscometer that continuously monitors the circulating blood of a living being undergoing a surgical procedure where knowledge of the being's current blood viscosity is crucial. The viscometer diverts a portion of a living being's circulating blood into a pair of riser tubes (R1, R2), connected together at upper and lower ends. The lower ends are connected through respective valves and a flow restrictor (52) of known dimensions. Through valve manipulation, the viscometer creates a respective blood column in each riser tube of a different height to establish a pressure differential between the columns. The blood columns are then placed into fluid communication through the flow restrictor and the changing heights of the columns are monitored over time. Using this data along with flow restrictor/riser tube dimensions, blood viscosity is calculated. The flow restrictor/riser tubes are then rinsed/dried in preparation for the next viscosity determination run.

Description

INLINE BLOOD VISCOMETER FOR CONTINUALLY MONITORING THE CIRCULATING BLOOD OF A LIVING BEING

SPECIFICATION

FIELD OF THE INVENTION

The invention pertains to methods and apparatus for measuring viscosity and more particularly, for apparatus and methods for continually detecting the viscosity of the circulating blood of a living being.

BACKGROUND OF INVENTION

The importance of determining the viscosity of blood is well-known. Fibroαen. Viscosity and White Blood Cell Count Are Major Risk Factors for Ischemic Heart Disease, by Yarnell et al., Circulation, Vol. 83, No. 3, March 1991 ; Postprandial Changes in Plasma and Serum Viscosity and Plasma Lipids and Lipoproteins After an Acute Test Meal, by Tangney, et al., American Journal for Clinical Nutrition, 65:36-40, 1997; Studies of Plasma Viscosity in Primary Hyperlipoproteinaemia. by Leonhardt et al., Atherosclerosis 28, 29-40, 1977; Effects of Lipoproteins on Plasma Viscosity, by Seplowitz, et al., Atherosclerosis 38, 89-95, 1981 ; Hvperviscositv Syndrome in a Hvpercholesterolemic Patient with Primary Biliary Cirrhosis, Rosenson, et al., Gastroenterology, Vol. 98, No. 5, 1990; Blood Viscosity and Risk of Cardiovascular Events:the Edinburgh Artery Study, by Lowe et al., British Journal of Hematology, 96, 168-171 , 1997; Blood Rheoloαv Associated with Cardiovascular Risk Factors and Chronic Cardiovascular Diseases: Results of an Epidemioloαic Cross-Sectional Study, by Koenig, et al., Angiology, The Journal of Vascular Diseases, November 1988; Importance of Blood Viscoelasticitv in Arteriosclerosis, by Hell, et al., Angiology, The Journal of Vascular Diseases, June, 1989; Thermal Method for Continuous Blood-Velocitv Measurements in Large Blood Vessels, and Cardiac-Output Determination, by Delanois, Medical and Biological Engineering, Vol. 11 , No. 2, March 1973; Fluid Mechanics in Atherosclerosis, by Nerem, et al., Handbook of Bioengineering, Chapter 21 , 1985.

Much effort has been made to develop apparatus and methods for determining the viscosity of blood. Theory and Design of Disposable Clinical Blood Viscometer, by Litt et al., Biorheology, 25, 697-712, 1988; Automated Measurement of Plasma Viscosity bv Capillary Viscometer. by Cooke, et al., Journal of Clinical Pathology 41 , 1213-1216, 1988: A Novel Computerized Viscometer/Rheometer by Jimenez and Kostic, Rev. Scientific Instruments 65, Vol 1 , January 1994; A New Instrument for the Measurement of Plasma-Viscosity, by John Harkness, The Lancet, pp. 280-281 , August 10, 1963; Blood Viscosity and Ravnaud's Disease, by Pringle, et al., The Lancet, pp. 1086-1089, May 22, 1965; Measurement of Blood Viscosity Using a Conicylindrical Viscometer, by Walker et al., Medical and Biological Engineering, pp. 551-557, September 1976.

One reference, namely, The Goldman Algorithm Revisited: Prospective Evaluation of a Computer-Derived Algorithm Versus Unaided Physician Judgment in Suspected Acute Mvocardial Infarction, by Qamar, et al., Am Heart J 138(4):705- 709, 1999, discusses the use of the Goldman algorithm for providing an indicator to acute myocardial infarction. The Goldman algorithm basically utilizes facts from a patient's history, physical examination and admission (emergency room) electrocardiogram to provide an AMI indicator.

In addition, there are a number of patents relating to blood viscosity measuring apparatus and methods. See for example, U.S. Patent Nos.: 3,342,063 (Smythe et al.); 3,720,097 (Kron); 3,999,538 (Philpot, Jr.); 4,083,363 (Philpot); 4,149,405 (Ringrose); 4,165,632 (Weber, et. al.); 4,517,830 (Gunn, deceased, et. al.); 4,519,239 (Kiesewetter, et. al.); 4,554,821 (Kiesewetter, et. al.); 4,858,127 (Kron, et. al.); 4,884,577 (Merrill); 4,947,678 (Hori et al.); 5,181 ,415 (Esvan et al.); 5,257,529 (Taniguchi et al.); 5,271 ,398 (Schlain et al.); and 5,447,440 (Davis, et. al.).

The Smythe '063 patent discloses an apparatus for measuring the viscosity of a blood sample based on the pressure detected in a conduit containing the blood sample. The Kron O97 patent discloses a method and apparatus for determining the blood viscosity using a flowmeter, a pressure source and a pressure transducer. The Philpot '538 patent discloses a method of determining blood viscosity by withdrawing blood from the vein at a constant pressure for a predetermined time period and from the volume of blood withdrawn. The Philpot "363 patent discloses an apparatus for determining blood viscosity using a hollow needle, a means for withdrawing and collecting blood from the vein via the hollow needle, a negative pressure measuring device and a timing device. The Ringrose '405 patent discloses a method for measuring the viscosity of blood by placing a sample of it on a support and directing a beam of light through the sample and then detecting the reflected light while vibrating the support at a given frequency and amplitude. The Weber '632 patent discloses a method and apparatus for determining the fluidity of blood by drawing the blood through a capillary tube measuring cell into a reservoir and then returning the blood back through the tube at a constant flow velocity and with the pressure difference between the ends of the capillary tube being directly related to the blood viscosity. The Gunn '830 patent discloses an apparatus for determining blood viscosity that utilizes a transparent hollow tube, a needle at one end, a plunger at the other end for creating a vacuum to extract a predetermined amount and an apertured weight member that is movable within the tube and is movable by gravity at a rate that is a function of the viscosity of the blood. The Kiesewetter '239 patent discloses an apparatus for determining the flow shear stress of suspensions, principally blood, using a measuring chamber comprised of a passage configuration that simulates the natural microcirculation of capillary passages in a being. The Kiesewetter '821 patent discloses another apparatus for determining the viscosity of fluids, particularly blood, that includes the use of two parallel branches of a flow loop in combination with a flow rate measuring device for measuring the flow in one of the branches for determining the blood viscosity. The Kron '127 patent discloses an apparatus and method for determining blood viscosity of a blood sample over a wide range of shear rates. The Merrill '577 patent discloses an apparatus and method for determining the blood viscosity of a blood sample using a hollow column in fluid communication with a chamber containing a porous bed and means for measuring the blood flow rate within the column. The Hori '678 patent discloses a method for measurement of the viscosity change in blood by disposing a temperature sensor in the blood flow and stimulating the blood so as to cause a viscosity change. The Esvan '415 patent discloses an apparatus that detects the change in viscosity of a blood sample based on the relative slip of a drive element and a driven element, which holds the blood sample, that are rotated. The Taniguchi '529 patent discloses a method and apparatus for determining the viscosity of liquids, e.g., a blood sample, utilizing a pair of vertically-aligned tubes coupled together via fine tubes while using a pressure sensor to measure the change of an internal tube pressure with the passage of time and the change of flow rate of the blood. The Bedingham '328 patent discloses an intravascular blood parameter sensing system that uses a catheter and probe having a plurality of sensors (e.g., an 0₂ sensor, CO₂ sensor, etc.) for measuring particular blood parameters in vivo. The Schlain '398 patent discloses a intra-vessel method and apparatus for detecting undesirable wall effect on blood parameter sensors and for moving such sensors to reduce or eliminate the wall effect. The Davis '440 patent discloses an apparatus for conducting a variety of assays that are responsive to a change in the viscosity of a sample fluid, e.g., blood.

Viscosity measuring methods and devices for fluids in general are well- known. See for example, U.S. Patent Nos.: 1 ,810,992 (Dallwitz-Wegner); 2,343,061 (Irany); 2,696,734 (Brunstrum et al.); 2,700,891 (Shafer); 2,934,944 (Eolkin); 3,071 ,961 (Heigl et al.); 3,116,630 (Piros); 3,137,161 (Lewis et al.); 3,138,950 (Welty et al.); 3,277,694 (Cannon et al.); 3,286,511 (Harkness); 3,435,665 (Tzentis); 3,520,179 (Reed); 3,604,247 (Gramain et al.); 3,666,999 (Moreland, Jr. et al.); 3,680,362 (Geerdes et al.); 3,699,804 (Gassmann et al.); 3,713,328 (Aritomi); 3,782,173 (Van Vessem et al.); 3,864,962 (Stark et al.); 3,908,441 (Virloget); 3,952,577 (Hayes et al.); 3,990,295 (Renovanz et al.); 4,149,405 (Ringrose); 4,302,965 (Johnson et al.); 4,426,878 (Price et al.); 4,432,761 (Dawe); 4,616,503 (Plungis et al.); 4,637,250 (Irvine, Jr. et al.); 4,680,957 (Dodd); 4,680,958 (Ruelle et al.); 4,750,351 (Ball); 4,856,322 (Langrick et al.); 4,899,575 (Chu et al.); 5,142,899 (Park et al.); 5,222,497 (Ono); 5,224,375 (You et al.); 5,257,529 (Taniguchi et al.); 5,327,778 (Park); and 5,365,776 (Lehmann et al.).

The following U.S. patents disclose viscosity or flow measuring devices, or liquid level detecting devices using optical monitoring: U.S. Patent Nos. 3,908,441 (Virloget); 5,099,698 (Kath, et. al.); 5,333,497 (Br nd Dag A. et al.). The Virloget '441 patent discloses a device for use in viscometer that detects the level of a liquid in a transparent tube using photodetection. The Kath '698 patent discloses an apparatus for optically scanning a rotameter flow gauge and determining the position of a float therein. The Br nd Dag A. '497 patent discloses a method and apparatus for continuous measurement of liquid flow velocity of two risers by a charge coupled device (CCD) sensor.

U.S. Patent No. 5,421 ,328 (Bedingham) discloses an intravascular blood parameter sensing system.

A statutory invention registration, H93 (Matta et al.) discloses an apparatus and method for measuring elongational viscosity of a test fluid using a movie or video camera to monitor a drop of the fluid under test.

The following publications discuss red blood cell deformability and/or devices used for determining such: Measurement of Human Red Blood Cell Deformability Using a Single Micropore on a Thin Si₃^ Film, by Ogura et al, IEEE Transactions on Biomedical Engineering, Vol. 38, No. 8, August 1991 ; the Pall BPF4 High Efficiency Leukocyte Removal Blood Processing Filter System, Pall Biomedical Products Corporation, 1993.

A device called the "Hevimet 40" has recently been advertised at www.hevimet.freeserve.co.uk. The Hevimet 40 device is stated to be a whole blood and plasma viscometer that tracks the meniscus of a blood sample that falls due to gravity through a capillary. While the Hevimet 40 device may be generally suitable for some whole blood or blood plasma viscosity determinations, it appears to exhibit several significant drawbacks. For example, among other things, the Hevimet 40 device appears to require the use of anti-coagulants. Moreover, this device relies on the assumption that the circulatory characteristics of the blood sample are for a period of 3 hours the same as that for the patient's circulating blood. That assumption may not be completely valid.

Notwithstanding the existence of the foregoing technology, there remains a need for an inline blood viscometer that provides for the continuous monitoring of the viscosity of the circulating blood of a living being that may be undergoing a surgical procedure, and where it is critical for the surgeon to know the living being's most current blood viscosity.

SUMMARY OF THE INVENTION

An apparatus for continuously determining the viscosity of the circulating blood of a living being over plural shear rates using a decreasing pressure differential. A method for continuously determining the viscosity of the circulating blood of a living being over plural shear rates using a decreasing pressure differential.

DESCRIPTION OF THE DRAWINGS

Fig. 1 is a diagrammatic view of the inline blood viscometer depicting a first column of blood being generated therein;

Fig. 2 is a diagrammatic view of the inline blood viscometer depicting a second column of blood being generated therein;

Fig. 3 is a diagrammatic view of the inline blood viscometer depicting the two columns of blood being placed into fluid communication with each other;

Fig. 4 is a diagrammatic view of the inline blood viscometer depicting how the flow restrictor path is rinsed and dried after a test run;

Fig. 5 is a diagrammatic view of the inline blood viscometer depicting how the riser tubes are rinsed and dried after a test run; and

Fig. 6 is a graphical representation of the height of the respective columns of blood over time in the riser tubes.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring now in detail to the various figures of the drawing wherein like reference characters refer to like parts, there is shown at 20 in Fig. 1 an inline blood viscometer for continually monitoring the circulating blood of a living being. The terms "continually" and "continuous" as used throughout this Specification means that once the apparatus 20 is coupled to the vascular system of the living being, the viscosity of the circulating blood can be repeatedly determined over time without human intervention.

The inline blood viscometer 20 basically comprises a pair of riser tubes, R1 and R2 that are coupled at their lower ends via respective valves, valve A and valve B, to a flow restrictor 52 (e.g., a capillary tube). As will be described in detail later, the circulating blood of the living being is diverted into this structure and respective columns of blood are formed in the two riser tubes R1 and R2. A decreasing pressure differential then causes the columns of blood to move in opposite directions through a plurality of shear rates, as the column of blood 82 in one riser tube (e.g., R1 ) falls and passes through the flow restrictor 52 which causes the column of blood 84 (Fig. 2) in the other riser tube, R2, to move upward. This movement of the columns of blood through a plurality of shear rates, along with the dimensions of the flow restrictor 52 and the riser tubes R1 and R2, are then used to calculate the viscosity of the circulating blood.

The operation of the inline blood viscometer 20 is similar to the dual riser/single capillary (DRSC) viscometer as described in A.S.N. 09/573,267, filed May 18, 2000, and A.S.N. 09/439,795 filed November 12, 1999, both entitled DUAL RISER/SINGLE CAPILLARY VISCOMETER, both assigned to the same Assignee as the present invention, namely Visco Technologies, Inc., and both of whose entire disclosures are incorporated by reference herein. The viscometers disclosed in those patent applications are also referred to as "circulating blood viscometers." The DRSC viscometer also includes a pair of riser tubes and a flow restrictor (e.g., a capillary tube) and utilizes a decreasing pressure differential to subject a pair of oppositely moving columns of fluid to move through a plurality of shear rates. The movement of these oppositely-moving columns is monitored over time to generate data related to these moving columns. This data, along with the dimensions of the flow restrictor and the riser tubes, are used to calculate the viscosity of the fluid.

In particular, as shown in Fig. 1 , the inline blood viscometer 20 comprises the riser tubes R1 and R2. The upper ends of the riser tubes R1 and R2 are coupled together through a conduit 22 which includes a valve C that can vent to the atmosphere. The lower end of riser tube R1 is coupled to valve A and the lower end of riser tube R2 is coupled to valve B. The flow restrictor 52 is coupled between valves A and B through a fourth valve D. Circulating blood from the blood vessel of the living being is inputted to the inline blood viscometer 20 through the input to valve A. Once the viscosity test is completed, the blood is discarded and the flow restrictor 52 path and the riser tubes R1 and R2 are rinsed (e.g., using a rinse pump 24) and then dried (e.g., using a dryer 29) in preparation for the next viscosity test run; this last step is important to move any residue (e.g., aggregated blood, coagulated blood, etc.) in these components and to dry them before the next viscosity test run. Furthermore, to monitor the changing columns of blood in the riser tubes R1 and R2, column level detectors 54 and 56 are provided. These column level detectors 54/56 are by way of example only and any method for detecting the changing height of the columns of blood 82/84 over time in the respective riser tubes R1 and R2 are contemplated by Applicants; this includes using mass detection (i.e., the changing mass in each of the riser tubes R1 and R2) as well as time of flight detection (using sound waves, including ultrasound, to monitor the level of each of the columns 82/84 over time). The details of the column level detectors 54 and 56 are provided in A.S.N. 09/439,795 and A.S.N. 09/573,267 and are not repeated here.

Although not shown, a computer (e.g., a "386" microprocessor or greater, or microcontroller or any equivalent) controls the valves A-D. In addition, the column level detectors 54/56 are also electrically coupled to the computer (also referred to as "processor") to provide the changing column height data to the computer for calculating the viscosity of the circulating blood. In addition, although not shown, the computer may comprise a monitor or panel for displaying the calculated viscosity value and other related data and/or this information can be provided to remote locations (e.g., printers, dataloggers, other computers) via global communication networks, e.g., the Internet.

It should be understood that although it is preferable to have each riser tube R1 and R2 in a vertical position, it is within the broadest scope of this invention to have the riser tubes R1 and R2 oriented at any angle, greater than zero degrees, with respect to a horizontal reference.

It should also be understood that modifying these circulating blood viscometers to include the conduit 22 and the valves A - D, the DRSC viscometer becomes a "closed-system" which permits the apparatus 20 to run automatically and which can be automatically rinsed and dried in preparation for the next viscosity determination run, and hence the "continuous" operation thereof.

The operation of the inline blood viscometer 20 is as follows: The blood vessel of the living being is coupled (e.g., a catheter, not shown) to the input of valve A which is positioned as shown in Fig. 1. As a result, the circulating blood of the living being is diverted into the inline blood viscometer 20 to form the column of blood 82 in riser tube R1. When the column of blood 82 reaches a predetermined height, h_1i; that is detected by the column level detector 54, the computer drives valves A and B into the positions shown in Fig. 2. This diverts the circulating blood through the flow restrictor 52, through valves D and B and up into riser tube R2 to form the second column of blood 84. When a predetermined height (different from hn) of the column of blood 84 is detected by the column level detector 56, a pressure differential is created between the column of fluid 82 and the column of fluid 84. The computer then drives valves A and C into the positions shown in Fig. 3. This action couples the two columns of blood 82 and 84 together through the flow restrictor 52 while cutting off the vent to atmosphere. The result of this action is that the column of blood 82 in riser tube R1 falls (see direction of arrow 31 ) while the column of blood 84 in riser tube R2 rises (see direction of arrow 33). As the column of blood 82 moves downward and the column of blood 84 moves upward, this movement causes the pressure differential to decrease, thereby causing the movement of the two columns 82/84 to slow down. The column level detectors 54/56 monitor the changing heights of the respective columns of blood 82/84 and provide that data to the computer (see Fig. 5). As discussed in detail in A.S.N. 09/573,267 and A.S.N. 09/439,795, the final levels of the columns of blood 82/84, namely, h^∞) and h₂(∞), respectively, are separated by a Δh(∞). This separation of the column heights can be attributed to surface tension, Δh_st and/or yield stress, τ_y , of the blood. As can be seen most clearly in Fig. 2, the presence of the

gas/fluid interface 85 for both columns of blood 82/84 accounts for the surface tension. As will be discussed later, a method for isolating the effects of surface tension Δh_st and yield stress τ is also incorporated into the apparatus/method of

the present invention 20.

Once the Δh(∞) is detected, the viscosity test run is complete and the computer calculates the viscosity of the circulating blood based on the changing height data (h^t), h₂(t), Δh(t)) along with the dimensions of the flow restrictor 52 and the riser tubes, R1/R2. At the same time, the computer then commands valves A - D to assume the positions shown in Fig. 4, while energizing the rinsing pump 24 (e.g., a miniature solenoid micro pump such as those sold by Bio-Chem Valve, Inc., of Boonton, NJ). The result of this action is to provide a rinsing and drying path for the flow restrictor 52 in order to discard the blood in the lower path by rinsing it with an IV solution and then drying that path using the dryer 29 (e.g., GCHIS-C05/120V small capacity/low flow heater by Omega Engineering of Stamford, CT). In particular, with the rinsing pump 24 activated and with valve A rotated as shown in Fig. 4, the input path from the vascular system of the living being is isolated while the blood in the flow restrictor 52 path is driven through valve B to be discarded (e.g., into a collector, drain, etc.); with valve C venting to atmosphere, the blood in the flow restrictor 52 path can be easily removed. The computer then de-activates the rinsing pump 24 and activates the dryer 29 for introducing hot air to dry the flow restrictor 52 path using the same valve positions. It should be noted that during rinsing, the dryer 29 acts merely as a conduit of the IV solution; conversely, when the dryer 29 is activated, no IV solution is passed to the dryer 29 from the rinsing pump 24. Next, the computer commands valves A - D into the positions shown in Fig. 5 in order to rinse/dry the riser tubes R1 and R2 through the conduit 22; the rinsing pump 24 and dryer 29 operate similarly as discussed with regard to the flow restrictor 52 path.

Once the riser tubes R1/R2 and conduit 22 are rinsed and dried, the computer de-activates the dryer 29 and commands valves A - D into the positions shown in Fig. 1 to prepare for a new set of columns of blood to be generated. Thus, the process is continuously repeated: diverting circulating blood into the inline blood viscometer 20 and establishing the oppositely moving columns of blood 82/84 which are then monitored, data generated and from which the blood viscosity is then determined, and then rinsing/drying the two paths.

As stated in A.S.N. 09/439,795, there are a plurality of mathematical models that can be used as curve fitting models for the data obtained from the DRSC viscometer such as a power law model, a Casson model, a Carreau model, a Herschel-Bulkley model, a Powell-Eyring model, a Cross model, Carreau-Yasuda model. It is within the broadest scope of this invention 20 to also include all of these models. The following discussion utilizes a power law model and is used by way of example only and not by way of limitation. Thus, one skilled in the art could substitute any of the above curve fitting models for the exemplary power law model discussed below

In particular, for non-Newtonian fluids, as is blood, the viscosity varies with shear rate, however, Hagen-Poiseuille flow within the capillary still holds for steady or quasi-steady laminar flow. For a fluid that is well-correlated with a non- Newtonian power law viscosity model, the capillary pressure drop and flow rate are related as follows:

where the shear rate, γ is related to the capillary flow rate by:

where the power law viscosity is defined as:

and where

ΔP_C = capillary tube pressure drop (Pa)

L_c = length of capillary tube (m)

Q = volumetric flow rate (m³/s) k = consistency index (a constant used in capillary viscometry) - that is determined; n = power law index (another constant used in capillary viscometry) -that is determined; φ_c = capillary tube diameter (m) μ = fluid viscosity (centipoise, CP) γ = shear rate (s^"1)

Since blood, a non-Newtonian fluid, is well-characterized with a power law viscosity model, Equation (1) can be re-written as:

+ h_stpg (4)

where p - blood fluid density; g = gravitational constant; h₁ = instantaneous height of the column of blood in riser R1 h₂ = instantaneous height of the column of blood in riser R2 φ_c = inside diameter of the capillary tube φ_r = inside diameter of riser tube and where φ_c «< φ_r Δh_st = an offset in column heights due to surface tension and/or yield stress τ_y of the blood.

It should be noted that the length of the capillary tube L_c is assumed large such that any friction forces in the riser tubes R1 and R2 and connecting fluid components can be ignored. In addition, the diameter of the riser tubes R1 and R2 are equal. By integrating both sides of Equation (4) with respect to time, the need to dh determine—— is eliminated, which yields: at

where h₀ = h₁(t) - h₂(t) at t=0; i.e., h₀ = h_ιr h_2i; and

In order to determine the viscosity, it is necessary to determine the values for k and n using curve fitting based on the test run data. In particular, the following procedure is used:

1) Conduct a test run and obtain all h^t) and h₂(t) data;

2) Fit curves through the data to obtain symbolic expressions for h^t) and h₂(t);

3) Determine all h^t) - h₂(t) data, as well as Δh_st;

3) Assume values for the power law parameters k and n;

4) Calculate the following error values for all data points:

Error [K - - (7)

6) Sum the error values for all data points; 7) Iterate to determine the values of k and n that minimize the error sum; and

8) Use the determined k and n values in Equations (2) and (3) to calculate viscosity.

As mentioned earlier, the apparatus and method of the present invention 20 also incorporates a method of isolating surface tension (Δh_st) and yield stress ( τ_y )effects as set forth in A.S.N. 09/708,137 filed on November 8, 2000 entitled

Method of Isolating Surface Tension & Yield Stress in Viscosity Measurements and which is assigned to the same Assignee as the present invention, namely Visco Technologies, Inc. Thus, the entire disclosure of A.S.N. 09/708,137 is incorporated by reference herein. As described in detail therein, the method basically comprises defining an expression for the pressure drop across the flow restrictor 52, in terms of the height of the columns of blood as: P_c(t) = giMt) - h₂(t) - Ah_st] (8) where Δh_st represents the height difference between the two columns of blood due to surface tension. The method also further comprises defining the yield stress of the blood as:

where ΔP(∞) is evaluated at t=∞ using Equation 8.

The method uses two alternative approaches for solving for Δh_st and τ_y and

thereby provides a mechanism for isolating the effects of these two components on the blood viscosity determination.

It should be understood that the pressure differential created between the columns of blood 82/84, pgΔh, where p is the density of the blood, ignores the density of the gas (e.g., air) that is trapped in the conduit 22 since the density of the gas is significantly smaller in comparison to the blood density.

It should be further noted that the conduit 22, the riser tubes R1/R2, the valves A-D, the pump 24 are all disposable as a set. Thus, when a new patient is to be coupled to the inline blood viscometer 20, a new set can be inserted. As with the devices disclosed in A.S.N. 09/573,267 and A.S.N. 09/439,795, although the riser tubes R1 and R2 are shown in vertical orientations, these riser tubes R1 and R2 could be positioned in at any angle greater than zero degrees with respect to a horizontal reference, e.g., the datum line.

It should be understood that, as explained in A.S.N. 09/573,267, due to the symmetry of the height vs. time data (see Fig. 6) for each of the columns of blood that move in the respective riser tubes, R1 and R2, it is not necessary to monitor both columns as they move; instead, only one column needs to be monitored over time while a single data point from the other column need only be taken. Thus, either column level detector 54 or 56 can be replaced by a single point detector; as further discussed in A.S.N. 09/573,267, it is preferable to monitor over time, the changing column level of the rising column while detecting a single data point from the falling column.

Without further elaboration, the foregoing will so fully illustrate our invention that others may, by applying current or future knowledge, readily adopt the same for use under various conditions of service.

Claims

1. An apparatus for continuously determining the viscosity of the circulating blood of a living being over plural shear rates using a decreasing pressure differential.

2. The apparatus of Claim 1 comprising a circulating blood viscometer coupled to the vascular system of the living being, said circulating blood viscometer comprising: a first lumen and a second lumen having respective upper ends and respective lower ends, said lumens being positioned at an angle, greater than zero degrees, to a horizontal reference, said respective upper ends being coupled together through a first valve, said first valve also being coupled to the vascular system of the living being, said first and second lumens having a first known dimension; a flow restrictor having a first end and a second end, said first end being coupled to the lower end of said first lumen through a second valve and wherein said second end is coupled to the lower end of said second lumen through a third valve, said flow restrictor having some known dimensions; a first sensor for detecting the movement of blood over time in either said first or second lumen and a second sensor for detecting a single data point from the other one of said first or second lumens, said first sensor generating data relating to the movement of the blood over time in said first or second lumen; a processor, coupled to said sensors and to said first, second and third valves, said processor arranged to operate said valves to create a first column of blood in said first lumen and a second column of blood in said second lumen and to establish a pressure differential between said columns of blood, said first column of blood moving through said first lumen and said flow restrictor and said second column of blood moving through said second lumen at a first shear rate caused by said pressure differential, said movement of said columns of blood causing said pressure differential to decrease from said first shear rate for generating said plural shear rates; and wherein said processor calculates the viscosity of the blood based on said data relating to the movement of blood in said first or second lumen over time, said single data point, said first dimension of said first or second lumen and said some known dimensions of said flow restrictor.

3. The apparatus of Claim 2 further comprising means for rinsing and drying said flow restrictor and said first and second lumens after calculating the viscosity of the blood.

4. The apparatus of Claim 3 wherein said means for rinsing and drying comprises: a fourth valve coupled between said second and third valves; a dryer coupled to said fourth valve; a pump coupled to said dryer, said pump being coupled to a source of rinsing solution; and wherein said fourth valve is arranged to operate with said first, second and third valves to permit said rinsing solution to be introduced into said flow restrictor by said pump and wherein said dryer is then activated to dry said flow restrictor, said fourth valve also being arranged to operate with said first, second and third valves to permit rinsing solution to be introduced into said first and second lumens by said pump and wherein said dryer is then activated to dry said first and second lumens.

5. The apparatus of Claim 2 wherein said first and second lumens are riser tubes that are positioned vertically with respect to said horizontal reference.

6. The apparatus of Claim 5 wherein said processor comprises an expression of a pressure drop across said flow restrictor in terms of the height of said columns of blood over time.

7. The apparatus of Claim 6 wherein said processor curve fits said expression of said pressure drop across said flow restrictor using said data relating to the movement of said columns of blood over time, said first dimension of said first or second lumen and said some known dimensions of said flow restrictor to determine the viscosity of the blood.

8. The apparatus of Claim 7 wherein said flow restrictor is a capillary tube and wherein said pressure drop across said capillary tube can be defined using a power law as follows:

where p = blood fluid density; g = gravitational constant;

L_c = length of said capillary tube; k = consistency index; n = power law index h₁ = instantaneous height of said column of blood in said first riser tube; h₂ = instantaneous height of said column of blood in said second riser tube; φ_c = inside diameter of said capillary tube; φ_r = inside diameter of said first and second riser tubes and where φ_c <« φ_r ; and

Δh_st = an offset of said column heights due to surface tension and yield stress of the blood.

9. The apparatus of Claim 8 wherein said processor calculates the yield stress, τ . , of the blood in accordance with the following:

Δ » - & ^τy = 4E

where,

ΔP_C(∞) is the pressure across said capillary tube after a long period of time and is given by:

ΔP_C(∞) = pg[h. (∞ ) - h₂{∞) - M _st ] ; and

where h^∞) is the height of said column of blood in said first riser tube after a long period of time; and h₂(∞) is the height of said column of blood in said second riser tube after a long period of time.

10. The apparatus of Claim 9 wherein said processor calculates the viscosity using h^t) - h₂(t) and Δh_st to determine said consistency index, k, and said power law index, n, as given by:

hι(t) - hι(t) - _h_st =

where

and where h₀ = h₁(0) - h₂(0).

11. The apparatus of Claim 10 wherein said processor calculates the viscosity, μ, using said determined values of n and k in the equation:

|Λ-1 μ = k\ ϊ where

and where

Q = volumetric flow rate in said capillary tube; and γ = shear rate.

12. The apparatus of Claim 1 comprising a circulating blood viscometer coupled to the vascular system of the living being, said circulating blood viscometer comprising: a first lumen and a second lumen having respective upper ends and respective lower ends, said lumens being positioned at an angle, greater than zero degrees, to a horizontal reference, said respective upper ends being coupled together through a first valve, said first valve also being coupled to the vascular system of the living being, said first and second lumens having a first known dimension; a flow restrictor having a first end and a second end, said first end being coupled to the lower end of said first lumen through a second valve and wherein said second end is coupled to the lower end of said second lumen through a third valve, said flow restrictor having some known dimensions; a respective sensor for detecting the movement of blood over time in said first and second lumens, said sensors generating data relating to the movement of the blood over time in said first and second lumens respectively; a processor, coupled to said sensors and to said first, second and third valves, said processor arranged to operate said valves to create a first column of blood in said first lumen and a second column of blood in said second lumen and to establish a pressure differential between said columns of blood, said first column of blood moving through said first lumen and said flow restrictor and said second column of blood moving through said second lumen at a first shear rate caused by said pressure differential, said movement of said columns of blood causing said pressure differential to decrease from said first shear rate for generating said plural shear rates; and wherein said processor calculates the viscosity of the blood based on said data relating to the movement of the columns of blood over time, said first known dimension of said first or second lumen and said some known dimensions of said flow restrictor.

13. The apparatus of Claim 12 further comprising means for rinsing and drying said flow restrictor and said first and second lumens after calculating the viscosity of the blood.

14. The apparatus of Claim 13 wherein said means for rinsing and drying comprises: a fourth valve coupled between said second and third valves; a dryer coupled to said fourth valve; a pump coupled to said dryer, said pump being coupled to a source of rinsing solution; and wherein said fourth valve is arranged to operate with said first, second and third valves to permit said rinsing solution to be introduced into said flow restrictor by said pump and wherein said dryer is then activated to dry said flow restrictor, said fourth valve also being arranged to operate with said first, second and third valves to permit rinsing solution to be introduced into said first and second lumens by said pump and wherein said dryer is then activated to dry said first and second lumens.

15. The apparatus of Claim 12 wherein said first and second lumens are riser tubes that are positioned vertically with respect to said horizontal reference.

16. The apparatus of Claim 15 wherein said processor comprises an expression of a pressure drop across said flow restrictor in terms of the height of said columns of blood over time.

17. The apparatus of Claim 16 wherein said processor curve fits said expression of said pressure drop across said flow restrictor using said data relating to the movement of said columns of blood over time, said first dimension of said first or second lumen and said some known dimensions of said flow restrictor to determine the viscosity of the blood.

18. The apparatus of Claim 17 wherein said flow restrictor is a capillary tube and wherein said pressure drop across said capillary tube can be defined using a power law as follows:

pg{hι - hi) + Δh_stpg

where p = blood fluid density; g = gravitational constant;

19. The apparatus of Claim 18 wherein said processor calculates the yield stress, τ , of the blood in accordance with the following:

where,

20. The apparatus of Claim 19 wherein said processor calculates the viscosity using h^t) - h₂(t) and Δh_st to determine said consistency index, k, and said power law index, n, as given by:

hι(t) - hι(t) - Ah_sl =

where

and where h₀ = h₁(0) - h₂(0).

21. The apparatus of Claim 20 wherein said processor calculates the viscosity, μ, using said determined values of n and k in the equation: μ = k where

and where

Q = volumetric flow rate in said capillary tube; and γ = shear rate.

22. A method for continuously determining the viscosity of the circulating blood of a living being over plural shear rates using a decreasing pressure differential.

23. The method of Claim 22 comprising the steps of:

(a) diverting a portion of the circulating blood of the living being;

(b) generating a pair of oppositely-moving columns of said diverted blood over plural shear rates using the decreasing pressure differential;

(c) monitoring the movement of one of said pair of oppositely- moving columns of blood over time and detecting a single data point from the other one of said oppositely-moving columns of blood to generate moving column data;

(d) determining the viscosity of the circulating blood from said moving column data;

(e) discarding said columns of blood; and

(f) repeating steps a - e.

24. The method of Claim 23 wherein said step of diverting a portion of the circulating blood of the living being comprises:

(a) providing a first and second lumen, each having upper ends and lower ends and wherein said upper ends are coupled together through a first valve and each lumen having a first known dimension, said first and second lumens being positioned at an angle, greater than zero degrees, to a horizontal reference;

(b) providing a flow restrictor having a first and second end and wherein said first end is coupled to the lower end of said first lumen through a second valve and wherein said second end is coupled to the lower end of said second lumen through a third valve, said flow restrictor having some known dimensions;

(c) coupling the vascular system to said second valve;

(d) venting said first valve to atmospheric pressure and diverting a portion of the circulating blood of a living being through said second valve into said first lumen to form a first column of blood therein; and

(e) diverting another portion of the circulating blood through said second valve, said flow restrictor and said second lumen to form a second column of blood in said flow restrictor and said second lumen and wherein a pressure differential is established between said columns of blood.

25. The method of Claim 24 wherein said step of generating a pair of oppositely-moving columns of said diverted blood comprises closing off said first valve from atmospheric pressure while operating said second and third valves to place said first and second columns of blood in fluid communication, said first column of blood moving through said first lumen and said flow restrictor and said second column of blood moving through said flow restrictor and said second lumen at a first shear rate caused by said pressure differential, said movement of said columns of blood causing said pressure differential to decrease from said first shear rate for generating said plural shear rates.

26. The method of Claim 25 wherein said step of monitoring the movement of one of said pair of columns of blood comprises providing a first sensor for detecting the movement of blood over time in either said first or second lumen and a second sensor for detecting a single data point from the other one of said first or second lumens, said first sensor generating data relating to the movement of the blood over time in said first or second lumen.

27. The method of Claim 26 wherein said step of determining the viscosity comprises calculating the viscosity of the blood based on said data relating to the movement of the blood over time in said first or second lumen, said single data point, said first dimension and said some known dimensions.

28. The method of Claim 27 wherein said step of discarding said columns of blood comprises discarding blood in said flow restrictor and said first and second lumens by rinsing and drying said flow restrictor and said first and second lumens.

29. The method of Claim 28 wherein said step of discarding blood in said flow restrictor and said first and second lumens comprises:

(a) venting said first valve to atmosphere;

(b) operating said second valve to isolate said flow restrictor from said first lumen;

(c) operating said third valve to couple said second lumen to a discard point;

(d) operating said fourth valve to couple a dryer and pump to said first end of said flow restrictor, said pump being coupled to a source of rinsing solution;

(e) activating said pump to pass said rinsing solution through said dryer, said fourth valve, said flow restrictor and through said third valve to said discard point;

(f) de-activating said pump and activating said dryer to dry said fourth valve and said flow restrictor;

(g) operating said first valve to couple said upper ends together;

(h) operating said third valve to de-couple said second end of said flow restrictor from said second lumen;

(i) operating said second and fourth valves to couple said dryer and pump to said first lumen;

(j) activating said pump to pass said rinsing solution through said dryer, said second valve, said first lumen, said first valve, said second lumen and through said third valve to said discard point; and (k) de-activating said pump and activating said dryer to dry said second valve, said first lumen, said first valve, said second lumen and said third valve.

(I) operating said fourth valve to de-couple said dryer and pump from said first end of said flow restrictor; and

(m) operating said second valve to couple said second valve to the vascular system.

30. The method of Claim 24 wherein said first and second lumens are riser tubes that are positioned vertically with respect to said horizontal reference.

31. The method of Claim 30 wherein said step of calculating the viscosity of the blood comprises using an expression for a pressure drop across said flow restrictor in terms of the height of said columns of blood over time.

32. The method of Claim 31 wherein said step of calculating the viscosity of the blood further comprises curve fitting said expression for said pressure drop across said flow restrictor using said data relating to the movement of said column of blood over time, said single data point, said first dimension of said first or second lumen and said some known dimensions of said flow restrictor.

33. The method of Claim 32 wherein said flow restrictor is a capillary tube and wherein said step of using an expression for a pressure drop comprises defining a power law as follows:

where p = blood fluid density; g = gravitational constant;

34. The method of Claim 33 wherein said step of calculating the viscosity of the blood comprises determining the yield stress, τ_y , of the blood in accordance

with the following:

Δ » - A ^τy = 4Z,

where,

ΔP_c(co ) = pg[h_x(∞ ) - /z₂ (∞ ) - i\h_st ] ; and

where h.,(∞) is the height of said column of blood in said first riser tube after a long period of time; and h₂(∞) is the height of said column of blood in said second riser tube after a long period of time.

35. The method of Claim 34 wherein said step of calculating the viscosity of the blood comprises using h.,(t) - h₂(t) and Δh_st to determine said consistency index, k, and said power law index, n, as given by:

hι(t) - hι(t) - Δh_st =

where

and where ho = h^O) - h₂(0).

36. The method of Claim 35 wherein said step of calculating the viscosity, μ, of the blood further comprises using said determined values of n and k in the equation: n-l μ = k r where

and where

Q = volumetric flow rate in said capillary tube; and γ = shear rate.

37. The method of Claim 22 comprising the steps of:

(a) diverting a portion of the circulating blood of the living being;

(c) monitoring the movement of said pair of oppositely-moving columns of blood over time to generate moving column data;

(e) discarding said columns of blood; and

(f) repeating steps a - e.

38. The method of Claim 37 wherein said step of diverting a portion of the circulating blood of the living being comprises:

(c) coupling the vascular system to said first valve; (d) venting said first valve to atmospheric pressure and diverting a portion of the circulating blood of a living being through said second valve into said first lumen to form a first column of blood therein; and

39. The method of Claim 38 wherein said step of generating a pair of oppositely-moving columns of said diverted blood comprises closing off said first valve from atmospheric pressure while operating said second and third valves to place said first and second columns of blood in fluid communication, said first column of blood moving through said first lumen and said flow restrictor and said second column of blood moving through said flow restrictor and said second lumen at a first shear rate caused by said pressure differential, said movement of said columns of blood causing said pressure differential to decrease from said first shear rate for generating said plural shear rates.

40. The method of Claim 39 wherein said step of monitoring the movement of said pair of oppositely-moving columns of blood comprises providing a respective sensor for detecting the movement of blood over time in said first and second lumens, said sensors generating data relating to the movement of the blood over time in said first and second lumens respectively;

41. The method of Claim 40 wherein said step of determining the viscosity comprises calculating the viscosity of the blood based on said data relating to the movement of the blood over time in said first and second lumens, said first known dimension and said some known dimensions.

42. The method of Claim 41 wherein said step of discarding said columns of blood comprises discarding blood in said flow restrictor and said first and second lumens by rinsing and drying said flow restrictor and said first and second lumens.

43. The method of Claim 42 wherein said step of discarding blood in said flow restrictor and said first and second lumens comprises: (a) venting said first valve to atmosphere;

(c) operating said third valve to couple said second lumen to a discard point;

(g) operating said first valve to couple said upper ends together;

(j) activating said pump to pass said rinsing solution through said dryer, said second valve, said first lumen, said first valve, said second lumen and through said third valve to said discard point; and

(k) de-activating said pump and activating said dryer to dry said second valve, said first lumen, said first valve, said second lumen and said third valve.

44. The method of Claim 38 wherein said first and second lumens are riser tubes that are positioned vertically with respect to said horizontal reference.

45. The method of Claim 44 wherein said step of calculating the viscosity of the blood comprises using an expression for a pressure drop across said flow restrictor in terms of the height of said columns of blood over time.

46. The method of Claim 45 wherein said step of calculating the viscosity of the blood further comprises curve fitting said expression for said pressure drop across said flow restrictor using said data relating to the movement of said columns of blood over time, said first dimension of said first or second lumen and said some known dimensions of said flow restrictor.

47. The method of Claim 46 wherein said flow restrictor is a capillary tube and wherein said step of using an expression for a pressure drop comprises defining a power law as follows:

where p = blood fluid density; g = gravitational constant;

L_c = length of said capillary tube; k = consistency index; n = power law index

In., = instantaneous height of said column of blood in said first riser tube; h₂ = instantaneous height of said column of blood in said second riser tube; φ_c = inside diameter of said capillary tube; φ_r = inside diameter of said first and second riser tubes and where φ_c <« φ_r ; and Δh_st = an offset of said column heights due to surface tension and yield stress of the blood.

48. The method of Claim 47 wherein said step of calculating the viscosity of the blood comprises determining the yield stress, τ_y , of the blood in accordance

with the following:

where, ΔP_C(∞) is the pressure across said capillary tube after a long period of time and is given by:

Δ _C(∞) = ρg[h_x{∞) - h₂(∞) -

and

49. The method of Claim 48 wherein said step of calculating the viscosity of the blood comprises using h^t) - h₂(t) and Δh_st to determine said consistency index, k, and said power law index, n, as given by:

hι(t) - hι(t) ~ Δλ,

where

and where ho = /0) - h₂(0).

50. The method of Claim 49 wherein said step of calculating the viscosity, μ, of the blood further comprises using said determined values of n and k in the equation: n-l μ = k 7

where

and where

Q = volumetric flow rate in said capillary tube; and γ = shear rate.

51. The method of Claim 22 comprising the steps:

(a) providing a circulating blood viscometer having a plurality of lumens and which has been modified to form a closed system;

(b) coupling said modified circulating blood viscometer between the vascular system of the living being and a discard point using a plurality of valves;

(c) operating said plurality of valves to generate a pair of oppositely-moving columns of blood from the circulating blood of the living being that move through plural shear rates using the decreasing pressure differential;

(d) monitoring the movement of one of said pair of oppositely- moving columns of blood and detecting a single data point from the

, other one of said oppositely-moving columns of blood to generate moving column data;

(e) determining the viscosity of the circulating blood based said moving column data and some known dimensions of said plurality of lumens; and

(f) discarding the blood in said plurality of lumens to the discard point by rinsing and drying said plurality of lumens; and

(g) repeating steps c - f.

52. The method of Claim 22 comprising the steps:

(c) operating said plurality of valves to generate a pair of oppositely-moving columns of blood from the circulating blood of the living being that move through plural shear rates using the decreasing pressure differential; (d) monitoring the movement of said pair of oppositely-moving columns of blood to generate moving column data;

(g) repeating steps c - f.