WO1996001990A1 - Rapid determination of blood sedimentation rate - Google Patents
Rapid determination of blood sedimentation rate Download PDFInfo
- Publication number
- WO1996001990A1 WO1996001990A1 PCT/US1995/008103 US9508103W WO9601990A1 WO 1996001990 A1 WO1996001990 A1 WO 1996001990A1 US 9508103 W US9508103 W US 9508103W WO 9601990 A1 WO9601990 A1 WO 9601990A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- specimen
- tube
- container
- lumen
- accomplished
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/04—Investigating sedimentation of particle suspensions
- G01N15/05—Investigating sedimentation of particle suspensions in blood
-
- G—PHYSICS
- G11—INFORMATION STORAGE
- G11C—STATIC STORES
- G11C16/00—Erasable programmable read-only memories
- G11C16/02—Erasable programmable read-only memories electrically programmable
- G11C16/04—Erasable programmable read-only memories electrically programmable using variable threshold transistors, e.g. FAMOS
-
- G—PHYSICS
- G11—INFORMATION STORAGE
- G11C—STATIC STORES
- G11C29/00—Checking stores for correct operation ; Subsequent repair; Testing stores during standby or offline operation
- G11C29/04—Detection or location of defective memory elements, e.g. cell constructio details, timing of test signals
- G11C29/50—Marginal testing, e.g. race, voltage or current testing
- G11C2029/5002—Characteristic
-
- G—PHYSICS
- G11—INFORMATION STORAGE
- G11C—STATIC STORES
- G11C29/00—Checking stores for correct operation ; Subsequent repair; Testing stores during standby or offline operation
- G11C29/04—Detection or location of defective memory elements, e.g. cell constructio details, timing of test signals
- G11C29/50—Marginal testing, e.g. race, voltage or current testing
- G11C2029/5006—Current
Definitions
- the present invention relates, in general, to a method and apparatus fordeterminingthe settling rate of solids in a liquid-solid mixture, and more particularly, relates to methods and apparatus for determining the erythrocyte or red blood cell sedimentation rate in whole blood.
- the original laboratory studies are still regarded as the standards. More particularly, there is a introbe sedimentation method and a Westergren sedimentation method.
- the Westergren method is most widely used and employs a 300 millimeter long settling tube with the lower 200 millimeters being graduated. The tube is filled to the 200 millimeter mark with approximately 0.8 milliliter of blood and 0.2 milliliters of anticoagulant diluent which is allowed to gravity settle over a one or a two hour period.
- the amount of settling in a one hour period in a Westergren settling tube is generally regarded as the standard for blood sedimentation rate.
- the specimen is first thoroughly mixed so that the erythrocytes are evenly distributed throughout the specimen.
- the 300 millimeter tube is brought to a vertical orientation for gravity settling and the settling clock started. After one hour the amount of settling which has occurred, as determined by the distance that the interface between the plasma and the erythrocytes has traveled downward, is measured.
- United States Patent No. 4,041,502 to Williams, et al. discloses an automated sedimentation measuring system which measurements are taken every 15 seconds for one hour (or two hours) and a blood sedimentation curve is produced as a result of these measurements.
- United States Patent No. 4,848,900 to Kuo, et al. is a similar blood sedimentation automated system in which a blood sedimentation curve is also generated over a one hour period.
- the erythrocytes While the erythrocytes are more dense than the plasma, they are small and thus have such a high surface area relative to volume that they do not readily sediment through plasma as single cells. In the initial or lag phase, therefore, the erythrocytes must come in contact with each other to group together in clumps or clusters known as "rouleaux.” Once a sufficient number of erythrocytes have grouped in rouleaux, the rouleauxwill begin to sediment through the blood plasma toward the bottom of the sedimentation tube. Thus, the initial sedimentation or lag phase may take 5 to 15 minutes for sufficient rouleaux clusters to form to enter the more rapid decantation phase. The lag phase portion of a sedimentation vs. time curve, therefore, is relatively flat and typically shows little sedimentation or movement of the plasma-erythrocyte separation interface.
- the settlingprocess involves both downward migration or sedimentation of the more dense erythrocytes in rouleaux and upward migration of the lighter plasma through the downwardly migrating rouleaux.
- the sedimentation rate increases significantly and is fairly linear in the decantation phase or the mid- range of the sedimentation process.
- the erythrocytes begin to packmore tightly at the bottom of the tube. This narrows the pathways for plasma to upwardly migrate to the plasma-erythrocyte separation boundary or interface.
- the plasma therefore, has amore difficult time escaping from between the red cells in rouleaux as the packing density or hematocrit rises. Sedimentation, therefore, again slows in this last or syneresis phase of sedimentation.
- accelerated blood sedimentation has been measured using tilted or inclined sedimentation tubes instead of vertically oriented tubes.
- a tube atube 100-200millimeters long and 2.5millimeters in diameter inclined at about 30 or 45 degrees from vertical
- settling rates can be measured after only 20 minutes of settling.
- the settling rate which is determined using such apparatus is not a true Westergren sedimentation rate because once again the relationship between the hematocrit rise and the entrapment of plasma is altered resulting in a nonlinear relationshipbetweenthetestmethod.
- the settling is non-linear and the measured rates must be related to Westergren rates by non-linear correlation algorithms. Tilting of the tube reduces the settling time by about two-thirds but because there is in this method no shortening of the lagphase, 20 minutes is still required and a non-linear correlation to Westergren rates is also necessary.
- non-linearalgorithms becomes less reliable in relatingresults toWestergren sedimentation rates as the sedimentation rate increases.
- High sedimentation rates usually indicate the presence of inflammatory conditions.
- the non-linear effects induced by rapid sedimentation tend to decrease the correlation accuracy to Westergren rates for specimens which are most affected by disease and other conditions sought to be discovered or analyzed by the sedimentation process.
- Another object of the present invention is to provide an erythrocyte sedimentation method and apparatus which can be used repeatedly on the same specimen to rapidly determine and verify the blood sedimentation rate.
- Another object of the present invention is to provide a blood sedimentation apparatus and method in which the whole blood specimen, from the moment of venipuncture, remains in a sealed container.
- Still a further object of the present invention is to provide a blood sedimentation apparatus and method in which smaller blood specimens are required and mixing of the blood specimen can be readily accomplished in very small volumes.
- Another object of the present invention is to provide an improved specimen container for use with processes requiring mixing of small liquid volumes.
- Still another object of the blood sedimentation apparatus and method of the present invention is to provide a sedimentation process having increased accuracy, relatively low cost, and suitability for semi-automated use by relatively unskilled paramedical personnel.
- the blood sedimentation method and apparatus of the present invention have other objects and features of advantage which will become apparent from, and are set forth in more detail in, the accompanying drawing and following Best Mode Of Carrying Out The Invention.
- the method of the present invention provides a process for accelerated determination of erythrocyte sedimentation inwholebloodwhich canbe correlatedwith averyhigh confidence level toWestergren settlingrates using linear data transposition.
- the present method greatly accelerates the lagphaseby using one of several techniques, accomplishes the gravity decantation phase rapidly by orienting the specimen container in a manner reducingthe time required for settling, and essentially eliminates the syneresis phase, again by orienting the specimen container to avoid plasma trapping as hematocrit rises.
- the method for accelerated determination of erythrocyte sedimentation of the present invention comprises, briefly, inducing rouleaux formation in a time period substantially less than the Westergren lag phase time period for the same specimen and in an amount sufficient for the specimen to enter the decantation phase.
- a portion of the specimen is formed into a very thin cross-section in the specimen container through which a fluid current is induced to flow so that contact between individual erythrocytes is enhanced and rouleaux formation in such portion occurs rapidly.
- This thin cross-sectional portion of the container is advantageously provided by a rod positioned inside the lumen of a tubular container and extending beyond the top surface of the specimen to cause a veil of specimen material to form by capillary attraction between the rod and container.
- the very thin cross-sectional portion of the specimen is oriented preferably at about 20 to about 30 degrees from horizontal for gravitational movement of the rapidly formed rouleaux down through the specimen to seed the specimen and commence the decantation phase.
- lagphase acceleration is accomplished by centrifugating the specimen, rather than creating a capillary veil, to form rouleaux rapidly.
- a confined cross-sectional portion of the specimen container is used and combined with a change of the specimen container configuration to accelerate 1990
- This form of lag phase acceleration is accomplished byholding a rod, for example magnetically, against an upper side of a horizontally oriented container lumen and then releasing the rod to gravitate down through the specimen to a lower side of the lumen.
- the present process further includes the step of gravity settling the erythrocytes, after rouleaux formation, with the specimen container oriented to substantially reduce the time required for the decantation phase below that which would be required in the Westergren process for the same specimen.
- gravity settling is accomplished, for example, by maintaining the specimen container oriented at 30 degrees or less to the horizon. This orientation, together with the presence of the rod on the upper side of the tube lumen, provides two protected channels through which plasma can escape thus significantly shortening the syneresis phase of sedimentation.
- the method of the present invention includes as a final step determining the amount of sedimentation which has occurred in the specimen, preferably by reorienting the specimen container from its near horizontal orientation for gravity settling to a near vertical orientation for sedimentation measurement.
- the apparatus for accelerated determination of erythrocyte sedimentation rate is comprised, briefly, of an elongated specimen tube having a lumen formed to contain a blood specimen therein and preferably including a very thin cross-sectional portion.
- the thin cross- sectional portion of the lumen advantageously can be provided by mounting a rod, adhesively or magnetically, in the specimen tube next to a wall of the tube and in a position to extend above a top surface of the specimen so that a veil of blood will form between the rod and tube wall.
- the present apparatus also includes specimen tube orienting assembly which can hold the specimen tube in a manner orienting it for accelerated rouleaux formation, for example at about 30 degrees from a horizontal plane.
- the orienting assembly also orients the specimen tube for accelerated gravity settling during the decantation phase, again at about 30 degrees or less to a horizontal plane.
- the orienting assembly is further formed to enable manipulation of the specimen tube to enable specimen mixing and reorientation from a gravity settling orientation to a sedimentation determination orientation.
- the orienting assembly is also formed for centrifugation of the specimentube, and in a second alternative embodiment the orientation assembly is formed to selectively hold and release a rod mounted in the specimen tube.
- a specimen container for mixing small volumes of liquid, such as blood specimens is provided.
- the specimen container has an elongated bore with an elongated member mounted therein to define a resulting elongated lumen with a channel portion of the cross sectional area of the lumen being formed to be sufficiently thin in transverse cross section that a liquid-mixinggasbubble cannot enterthis channel portion of the lumen and the liquid can flow along the channel.
- FIGURE 1 is a top perspective view of an erythrocyte sedimentation apparatus constructed in accordance with the present invention.
- FIGURE 2 is a top perspective view corresponding to FIGURE 1 with the blood specimen tubes oriented for accelerated rouleaux formation and gravity settling.
- FIGURE 3 is an enlarged, top plan view in cross section of the apparatus taken substantially along line 3-3 in FIGURE 1.
- FIGURE 4 is a greatly enlarged, side elevation view, in cross section, of a specimen container tube constructed in accordance with the present invention.
- FIGURE 5 is an end view, in cross section, taken substantially along the plane of line 5-5 in FIGURE 4.
- FIGURE 6 is a graph of sedimentation rate data using the apparatus of FIGURES 1-5, as compared to Westergren sedimentation data formodified blood specimens from the same patients.
- FIGURE 7 is a top perspective view of an alternative embodiment of an erythrocyte sedimentation apparatus constructed in accordance with the present invention.
- FIGURE 8 is an enlarged, side elevation view, in cross section, of a specimen container designed for use with the apparatus of FIGURE 7.
- FIGURE 9 is a further enlarged, cross sectional view taken substantially alongthe plane of line 9-9 in FIGURE 8.
- FIGURE 9A is a cross sectional view corresponding to FIGURE 9 of an alternative embodiment of the specimen collection tube of FIGURE 8.
- FIGURE 9B is a cross sectional view corresponding to FIGURE 9 of another alternative embodiment of the specimen collection tube of FIGURE 8.
- FIGURE 10 is a schematic representation of the specimen tube of FIGURE 8 after drawing of a specimen.
- FIGURE 11 is a schematic representation of the specimen tube of FIGURE 8 during mixing.
- FIGURE 12 is a schematic representation of the specimen tube of FIGURE 8 during centrifuging.
- FIGURE 13 is a schematic representation of the specimen tube of FIGURE 2 at the start of gravity settling.
- FIGURE 13A is an enlarged, cross sectional view of the specimen tube at the start of settling.
- FIGURE 13B is an enlarged, cross sectional view of the specimen tube after significant settling has occurred.
- FIGURE 14 is a schematic representation of the specimen tube of FIGURE 8 during the step of determining the amount of sedimentation.
- FIGURE 15 is a graph of sedimentation rate data using the apparatus of FIGURES 7 and 8, as compared to Westergren sedimentation data for unmodified blood specimens from the same patients.
- FIGURE 16 is a graph of sedimentation rate data using the apparatus of FIGURES 7 and 8, as compared to Westergren sedimentation data for modified blood specimens from the same patients.
- FIGURE 17 is a side elevation view, in cross section of an alternative embodiment of a specimen container constructed in accordance with the present invention.
- Themethod andapparatus ofthepresent invention achieve rapid erythrocyte sedimentation results which can be linearly related to Westergren sedimentation results.
- Essentially two key principles are employed to greatly accelerate the time required for sedimentation.
- the lag phase of the conventional Westergren sedimentationmethod is acceleratedby inducingrouleaux formation in the specimen rapidly, until there is sufficient rouleaux to cause erythrocyte settling at substantially the decantation rate for the specimen.
- the specimen is gravity settled in a container formed and oriented so that the erythrocytes can settle through upwardly migrating plasma in a manner which is substantially unimpeded by the increasing hematocrit.
- the method and apparatus of the present invention allow a blood specimen sedimentation to be accelerated across the lag phase, gravity settled through the decantation phase in a much shorter period of time, and settling in the syneresis phase to essentially be eliminated.
- the result is that sedimentation data that can be linearly transposed to Westergren data can be obtained in five minutes or less.
- the first step of the present process is to accelerate sedimentation by greatly reducing the time which would normally be required for the specimen to pass through the lag phase and begin the linear decantation phase.
- Several techniques for acceleration of blood sedimentation through the lag phase have been discovered andwill be describedherein, but thepreferredtechnique can be described by reference to a specimen tube which is particularly well suited for use in the method of the present and is shown in FIGURES 4 and 5. Essentially the same tube also is shown in FIGURES 8 and 9.
- specimen tube 21 is formed with a tube wall 22 which defines a tube lumen 23.
- Lumen 23 terminates in an open end 24 having a rubber stopper or other end closure member 26 mounted therein.
- specimen tube 21 advantageously can be a partially evacuated, blood specimen tube having a length of about 110 millimeters and a lumen diameter of about 6 millimeters.
- An anti ⁇ coagulant is placed in the tube before the specimen is drawn.
- the specimen is taken by a needle 159 (shown in broken lines in FIGURE 8) which extends through stopper 26 in a conventional manner, and such blood specimen tubes, as thus far described and blood specimen drawing techniques, are well known in the medical profession.
- tube 21 preferably has an elongated member or rod 27 mounted in the lumen.
- Rod 27 is preferably about 4 millimeters in diameter and is secured or held by adhesive, fused glass or other means, against one side of lumen 23, in this case the upwardly oriented side 28.
- tube 21 has a substantially cylindrical lumen 23 and elongated member 27 is a cylindrical rod, but other lumen-rod configurations are suitable for use in the present invention.
- the Westergren lag phase can require 5 to 15 minutes to complete.
- rouleaux must be formed from individual erythrocytes in sufficient number to seed the specimen and start the linear or decantation phase of sedimentation.
- rouleaux formation is induced at an accelerated rate and sufficient rouleaux created to begin the decantation phase in a matter of seconds, for example, 30 seconds or less.
- the preferred manner of accelerating rouleaux formation is to provide a specimen container which will have a very thin cross- sectional area in one portion of lumen 23.
- the combination of cylindrical rod 27 and cylindrical lumen 23 is that two areas of small cross-section, namely, horn-like areas 31 and 32, exist proximate upper side 28 of lumen 23.
- blood specimen 29 in these areas is at least somewhat confined.
- horn-shaped cross-sectional areas 31 and 32 are "small” or “thin” in cross section, in the absence of lengthwise current induced by the exaggerated settling of rouleaux in the veils, they do not by themselves produce the accelerated rouleaux formation of the method of the present invention.
- upper end 33 of rod 27 protrudes above top surface 34 or the meniscus of specimen 29 for a tube oriented as shown, in this case, oriented at an angle of 30 degrees to a horizontal plane 36.
- the blood specimen forms an arcuate veil-like volume 37 in each of horn areas 31 and 32 proximate and up to the upper end 33 of rod 27. While impractical to show in the drawing, very thin specimen veil 37 will extend up rod 27 by capillary action to the last point of contact 38 of the rod with tube upper side wall 22.
- the amount of the specimen in the upper reaches of veil region 37 is small as compared to the entire specimen 29. It is believed, however, that rouleaux are starting to form elsewhere in the specimen and particularly in small cross-sectional horns 31 and
- rouleaux formed in very thin upper region of veil 37 are immediately free to gravitate downwardly along veil 37 and across rod 27, and as they do so plasma is pulled up along horned regions 31 and 32 between the rod and tube and into veil region 37.
- the orientation of tube 21 is such that rouleaux can escape veil region 37 and plasma can enter the veil 1990
- rod 27 should extend above upper specimen meniscus by at least 3 to 4 millimeters for optimum acceleration effect, but any protrusion starts to provide a thinned capillary veil which should be useful.
- the maximum useful protrusion similarly is not known, but blood specimens will rise up to an inch or more abovemeniscus surface 34 along thin capillary-like channels, such as horns 31 and 32.
- tube 21 which is best suited for both accelerated rouleaux formation and gravity settling during the decantation phase is believed to be between about 20 degrees to about 35 degrees from the horizon. Most preferably tube 21 is oriented at about 30 degrees from horizontal plane 36 during both accelerated rouleaux formation and gravity settling during the decantation phase. As tube 21 is lowered to an orientation below about 25 degrees, circulation of plasma up along horns 31 and 32 is reduced and sedimentation times begin to increase. Similarly, as tube orientation is increased to above about 35 degrees egress of plasma becomes impeded by settling of red cell aggregates which, at these higher angles no longer seed the sedimentation process but instead impede plasma egress.
- the next step in the process of the present invention is to gravity settle the specimen, which is now through the lag phase of sedimentation.
- the middle or decantation phase tends to be relatively linear until the hematocrit increases significantly and the settled erythrocytes trap or impede upward migration of plasma at the bottom of the specimen tube, that is the specimen enters the syneresis phase.
- specimen container21 is oriented in a manner enabling settling of erythrocyte cells through upwardly migrating plasma without trapping or impeding of the plasma as a result of the relatively small transverse cross sectional area of the tube.
- Westergren tubes, and settling tube 21 both have relatively small diameters in order that the amount of whole blood required to perform sedimentation testing can be minimized, but it is the small diameter which causes the slowing of sedimentation at the end of the settling period.
- the time required for the linear decantation phase is greatly shortened and the syneresis phase is substantially eliminated by orienting specimen tube 21 with its longitudinal axis 55 of specimen tube 21 in a near horizontal orientation, as shown in FIGURE 4.
- near horizontal shall mean between about 35 degrees and about zero degrees from the horizon. Orienting longitudinal axis 55 in a nearhorizontal plane cause the transverse area of specimen tube 21 to be greatly increased as compared to the transverse area (FIGURE 5) of a vertically-oriented tube 21.
- Such an orientation of the specimen tube 21 will cause the rouleaux in the specimen tube to simultaneously gravitate or fall across the relatively small diameter of the tube, but over a relatively large area of the tube.
- the resistance to downward movement of rouleaux and to upward migration of plasma in the tube as a result of the large horizontal area of the near-horizontal, elongatedtube substantially eliminates impeding, choking or slowing down of the sedimentation rate.
- the syneresis phase as a result of dramatically increasinghematocrit and resultant trapping of plasma by the erythrocytes, is substantially eliminated.
- the rouleaux move or settle down through the plasma in a manner which is very close to or approximates settling in a bottomless tube.
- the hematocrit or blood cell packing density buildup hasvery little effect intrappingplasma because of the large transverse or horizontal area and of the very short distance need for plasma travel to escape the settling erythrocytes.
- the time required for completion of the decantation or linear settling phase is much less. It has been determined that, after about 3.5 to about 5.0 minutes of gravity settling with the specimen tube in a horizontal orientation, the decantation or linear sedimentation phase is completed in a degree which is substantially equal to, and correlatable with, 60 minutes of settling using the Westergren method.
- the next step in the process of the present invention is to determine the amount of settling which has occurred during the period of time which the lag phase was accelerated and the decantation phase was taking place, for example, 5.0 minutes.
- tube 21 can be rotated to a near vertical orientation, for example, to about 90 degrees from the horizon.
- the reorientation of the specimen tube to a nearvertical position will cause the settled cells to reach the bottom of the tube quickly, and a measurement of the separation boundary or interface between the plasma and settled cells can be taken, for example, as soon as five seconds after reaching a vertical orientation.
- a measurement of the separation boundary or interface between the plasma and settled cells can be taken, for example, as soon as five seconds after reaching a vertical orientation.
- the tube may, however, be read in a semi-vertical position with a modest increase in associated reading error.
- the steps of accelerated induction of rouleaux formation, gravity settling in an orientation shortening the decantation phase and determining the amount of settling can be implemented by hand by a laboratory technician.
- a technician can easily perform the procedure of the present invention without automation or special equipment.
- FIGURES 1 through 3 show one form of sedimentation tube manipulating apparatus 20 which can be used to perform the present process.
- Sedimentation apparatus 20 preferably includes a base 41 having leveling assembly, such as manually engageable leveling screws 42 and a spirit level 43, so that the apparatus can be leveled for reproducible results on a laboratory bench top.
- leveling assembly such as manually engageable leveling screws 42 and a spirit level 43, so that the apparatus can be leveled for reproducible results on a laboratory bench top.
- mounted on base 41 is a housing
- a light source such as two U-shaped fluorescent tubes 46 and 47 (FIGURE 3) , are positioned.
- a rotatable tubeholder assembly is mounted to extend from front panel 44 of housing 43.
- assembly 48 includes a central U-shaped frame member 49 mounted by collar 51 to a shaft 52 for rotation therewith. Secured by fasteners to U-shaped frame member 49 are tube holder members 53 and 54.
- Each of the tube holder housings 53 and 54 includes a slotted or windowed front opening 56 with sedimentation measuring indicia 57 positioned closely proximate thereto.
- the back side 58 of housings 53 and 54 is open so that light may enter the housing and fall upon tubes 21.
- Housings 53 and 54 further include two mounting support felts (not shown) which receive and firmlyholdthe tubes in the housings without interfering with the passage of light through the tubes and out slots 56.
- the tubes 21 are mounted in housings 53 and 54 with rod 27 on the same side of the respective housings so that when assembly 48 is stopped in the position shown in FIGURE 2, rods 27 will be oriented inside tubes 21 essentially as shown in FIGURE 4.
- Shaft 52 extends through front wall 44 of housing 43 and completely through the housing and out back wall 59.
- a first spur gear 61 is mounted on the end of shaft 52 and cooperatively engages a pinion 63 carried by shaft 64 of motor 66.
- Mounted interiorly of housing 43 is an indexing disk 67 which is fixed for rotation with shaft 52 by collar 68.
- a magnet 69 and a ferromagnetic collar 71 coupled to shaft 52.
- an indexing detent assembly 72 and light ballasts 73 also are mounted inside housing 43.
- the first step of the present invention is to thoroughly mix specimen 29 in specimen tube 21.
- Mixing insures that there is no pre-formed rouleaux in the specimen, and mixing thoroughly mixes the anti-coagulant material in the specimen tube with the whole blood that has been drawn.
- Apparatus 20, therefore, preferably is constructed in a manner which will manipulate tube 21 so as to effect mixing.
- one of the substantial advantages of the construction of specimen tube 21 in which rod 27 is positioned in lumen 23 is that the gas bubble which will always be present in the tube can be used as a mixing device.
- the bubble will move from one end of the tube to the other, with the blood/anti-coagulant moving in the opposite direction.
- One of the substantial problems in connection with mixing small liquid volumes is that in small diametertubes gas bubbles or the like will bridge, rather than move up and down the tube, and prevent mixing.
- the presence of the rod in lumen 23 enables the blood/anti-coagulant to pass beyond the bubble in horn regions 31 and 32, because the bubble cannot enter into the thin transverse cross section horn regions.
- motor switch 74 can be turned on and the motor 66 will slowly rotate the holder assembly 48 when the shaft and gears are in the solid line positions shown in FIGURE 3.
- gear 61 is engaged with gear 63 and assembly 48 is positioned out away from front panel 44 of housing 43.
- the gearing and motor speed can be set so that rotation occurs at about 1990 _
- indexing disk 67 can have two notches which receive detent element 76 when the notches are in indexed relation to element 76.
- the indexing disk 67 is fixed by a collar for rotation with shaft 52 and has a first notch at a location which will secure tube holder assembly 48 in the position shown in FIGURE 2, namely, at an angle of about 30 degrees to a horizontal plane.
- a second notch is provided in indexing disk 67 which will hold tube holder assembly 48 in the position of FIGURE 1, namely, in a near vertical position.
- the technician turns motor switch 74 off, pushes tube holder assembly 48 inwardlyto apositioncloselyadjacenttotranslucent front panel 44 and rotates the assembly to the position of FIGURE 2, at which it is held in place by detent element 76 engaging a notch indexing disk 67.
- the assembly is left in this position for five minutes.
- the technician can then manually rotate assembly 48 from the FIGURE 2 position to the FIGURE 1 position, at which point detent 76 will engage a second notch indexing disk 67, holding the assembly as shown in FIGURE 1.
- the technician can then read the location of the plasma/erythrocyte interface using indicia 57 on the front of tube holder housings 53 and 54.
- each blood specimen 29 can repeatedly have its sedimentation rate tested. Accordingly, the technician normally will complete the measurement process and then return the tube holder assembly to the FIGURE 3 solid line position and turn on the motor to re-mix the specimen. It should be noted, of course, that light switch 77 should be turned on so that reading of the plasma/erythrocyte interface or boundary can be easily accomplished by back lighting of the specimen through opening 58.
- FIGURE 6 shows a graph of sedimentation results obtained using apparatus 20 and the process of the present invention. These results have been compared to Westergren sedimentation rates for the same specimens.
- the specimens are whole blood specimens which have been modified in the laboratory to change their sedimentation rate in a manner well known and set forth in the blood sedimentation literature.
- specimen tube 21 and 121 of the present invention a method and apparatus for mixing constituents of a small volume of liquid in a container having a small cross section is provided by the preferred form of specimen tube 21 and 121 of the present invention, as shown in FIGURES 4 and 8 of the drawings.
- specimen tubes 21, 121 canbe elongatedtubularmembershaving a central lumen 23,151 extending along the length of the tube.
- An elongated member 27, 152 is mounted in the lumen and preferably extends over a majority of the length of the lumen.
- Elongated member 27,152 can be secured to an interior surface of the tube along one side of the tube, for example, by an ultraviolet-activated adhesive 153, or by other means, such as fusing a glass member to the interior of a glass tube, or magnetically holding the rod to a side of the tube, which will be described in more detail hereinafter.
- tube 21 is similarly constructed.
- the specimen tube wall 150 andmember 152 define therebetween a lumen 151 having a transverse cross section configuration which will prevent a gas bubble from completely filling the cross section of the lumen, whichwould prevent the liquid from passing beyond the gas bubble as it rises in the tube. This can be accomplished, for example, by providing a wedge-shaped transverse area.
- a tube 121 having a cylindrical bore with an elongated cylindrical rod 152 mounted therein will define therebetween a lumen 151 which is crescent-shaped intransverse cross sectionandhas twowedge-shapedhorn regions or converging areas 156 at ends of the crescent.
- specimen tube 121 are vacuum tubes which contains a predetermined amount of specimen diluent, such as, about 0.25 milliliters anticoagulant material, suitable for mixing with a 1.0 millilitervolume ofwhole blood.
- specimen diluent such as, about 0.25 milliliters anticoagulant material
- Suchvacuum tubes with anticoagulant and a vacuum which will draw a predetermined known amount of blood specimen are well known in the art.
- These vacuum tubes do not have elongated member 27, 152 mounted therein.
- the vacuum tube container 21, 121 of the present invention therefore, includes a rubber end stopper 26, 158 through which a needle 159 can be inserted.
- the inner end 161 ofthe needle preferablyshouldnotcontactthe outermost end 162 of member 152.
- end 162 of member 152 is recessed by an amount (for example, one-half centimeter) to allow inner end 161 of needle 159 to clear member 152.
- specimen container 21, 121 Since it is not possible to draw a perfect vacuum inside specimen tube 121, therewill always be some gas, usually air, trapped in the vacuum tube. When a specimen is drawn, therefore, it will be pulled into lumen 151 by the vacuum therein until the lumen between the tube and elongated member is substantially filled (about 1.25 milliliters) , with the exception of a small air bubble 157. Air bubble 157 can then be used to mix liquid after needle 159 is removed from rubber stopper 158.
- a major advantage of specimen container 21, 121 and the method and apparatus of the present invention is that at all times the blood specimen is sealed in container 21, 121. Thus, the danger to technicians from handling whole blood is greatly reduced. Moreover, the same specimen can be used in the sealed container to repeat the sedimentation process.
- specimen tube 121 includes a stopper 58 having a diameter greater than the tube body. This will result in a slight tilt to the specimen tube, for example, of 2-4 degrees, from the horizon when tube 121 is placed in a horizontally oriented trough 137.
- This has the advantage that it ensures that bubble 157 will be up at stopper 158 so that the bubble will not cause remixing when the tube is reoriented to a near vertical orientation to determine the amount of settling. It is a feature of the present process, therefore, to effect gravity settlingwith container 121 orientedwith upper end or stopper 158 tilted up from horizontal by about 1 degree to about 6 degrees.
- FIGURE 9A still a further alternative embodiment 121a of the specimen container of the present invention is shown.
- An elongated plastic insert member 181 is positioned in lumen 151a of tube 121a.
- the plastic insert includes horn regions or wedge-shaped cross sectional areas 156a into which a gas cannot extend.
- the liquid in tube 121a will pass beyond the gas bubble in areas 156a as the tube is tilted.
- a tube constructed as shown in FIGURE 9A if oriented with one horn region 156a uppermost, and if a very thin section extended upwardly beyond the specimen upper surface 34, would accelerate rouleaux formation and be suitable for use in apparatus 21.
- Still a further alternative tube embodiment is shown in FIGURE 9B.
- Tube 121b has been formed to provide the narrow cross sectional areas 156b by, for example, deforming a heated glass tube to provide narrow areas 156b. Again, areas 156b are sufficiently narrow to prevent a gas from entering these areas, and the liquid can move past the bubble in these areas. Whether or not glass fabrication techniques will allow a sufficiently thin horn region 156 to be formed to allow use of the accelerated rouleaux formation technique described in connection with FIGURES 4 and 5 is unknown.
- Sedimentation apparatus 120 preferably employs a centrifuge assembly as a means for inducingrouleaux formation intheblood specimen.
- centrifuge assembly 122 includes a rotatable turntable 124 on which tube receiving head 126 is mounted.
- a plurality of elongated tube receiving notches 127 are formed in head 126 and a tube retaining means, such as brand 128, can be mounted over head 126 so as to retain specimen tubes 121 in notches 126 during rotation of the centrifuge.
- Various other forms of tube retaining structures are suitable for use with centrifuge 122.
- Turntable 124 is mounted to a drive controller assembly 129. Power can be controlled through on-off switch 131, the spin rate by control knob 130 and the spin duration through knob 135.
- Centrifuge assembly 122 of the present invention can be provided by any one of a number of standard laboratory centrifuges as long as they are capable of spinning elongated specimen tubes 121 with the longitudinal axis thereof generally parallel to the spin axis of the centrifuge at a rate high enough to induce rouleaux formation in an amount sufficient to cause erythrocyte settling to begin at substantially the decantation rate for the specimen in a short period of time.
- Centrifuge assembly 122 accelerates the specimen with a centrifugal force that preferably is in the range of about 5 to 10 times the acceleration of gravity, g.
- a centrifuge operating at about 400 rpm with a distance from the spin axis to the center of the specimen tube of about 4 centimeters will produce sufficient centrifugal force to cause the somewhat more dense erythrocytes to migrate through the plasma to the outermost surface defining the specimen tube bore or lumen.
- the erythrocytes are driven to the tube side, they come in contact with each other and begin to adhere together to form rouleaux which are held against the outer side of the lumen by the centrifugal force. After about 20 to 45 seconds, sufficient rouleaux will be formed on the outer side of the specimen tube lumen so that, if the rouleaux are allowed to gravitate, theywill begin settling of the specimen at the decantation rate.
- the next step in the process of the present invention is to gravity settle the specimen, which is now through the lag phase of sedimentation.
- Specimen container 121 again is oriented in a manner for settlingof erythrocyte cells throughupwardlymigrating plasma without being constricted or impeded by the relatively small cross sectional area of tube 121.
- This canbe accomplished using the preferred elongated, small diameter specimen tube by placing the specimen tube in manipulation apparatus 123 with the longitudinal axis 155 of specimen tube 121 in a near horizontal orientation, in this case essentially zero degrees or in a horizontal plane, as shown in FIGURES 7 and 8.
- Orienting axis 155 in a substantially horizontal plane cause the transverse area of the specimen tube to be greatly increased as compared to a vertically-oriented tube 121.
- the outer side 160 of the specimen tube, against which the rouleaux were formed by centrifugation is oriented in an uppermost position.
- specimen tubes 121 are transferred from centrifuge head 126 to a support member 136, which has a plurality of tube-receiving mounting structures, such as troughs or grooves 137.
- Specimen container 121 is oriented with its longitudinal axis 155 horizontal and side 160, which was facing outwardly in the centrifuge, facing upwardly on tube support member 136. This results in rod 152 in tube 121 being on bottom side 150 of the tube, which is just opposite of the position of rod 27 in tube 21 during decantation.
- the distance across the tube diameter is short, and the time required for completion of the decantation or linear settling phase is much less than for the Westergren process.
- the decantation or linear sedimentation phase is completed to a degree which is substantially equal to, and correlatable with, 60 minutes of settling using the Westergren method.
- sedimentation apparatus 120 reorient specimen container 121 to a near vertical position.
- support member 136 can be rotated to a nearvertical orientation, for example, to about 80 degrees from the horizon. This causes the settled erythrocytes to slip down the bottom side of the specimen tube 121 and the plasma on upper side 160 of the lumen 151 to float up the opposite side of the tube to the top.
- container orientation assembly 123 preferably includes support axle 139 and control and motor assembly 141 which can be used to rotate tube support member 136 from a horizontal to a near vertical position in a slow but smooth reorienting step.
- Apparatus 123 also may include means (not shown) for retaining each of tubes 121 in troughs 137 during their orientation to a near vertical position, although since they do not go beyond vertical, tubes 121 can be retained in troughs 137 by means of gravity.
- the step of mixing the blood specimen be undertaken immediatelyprior to inducing rouleaux formation.
- sedimentation apparatus 120, and particularly container- orienting apparatus 123, of the present invention preferably is formedtomixtheblood specimenthoroughly justpriortothe centrifugingorrouleaux inducingstep.
- Sedimentation apparatus 120 preferably includes a controller 141, which includes a mixer input 142 that will cause tube support member 136 to oscillate about a horizontal axis, for example, about axle 139.
- a controller 141 which includes a mixer input 142 that will cause tube support member 136 to oscillate about a horizontal axis, for example, about axle 139.
- Such oscillation or tilting can be used to cause a gas bubble or a glass bead (not shown) to migrate from one end of specimen container 121 to the other. It would also be possible to effect mixing by a continuing rotating process, but then retention means for the specimen containers clearly would be required.
- an air bubble in the specimen container is allowed to migrate from one end of the container to the other by tilting specimen container 121 by about 60 degrees to 75 degrees from the horizon in one direction and then by about the same amount from the horizon in the opposite direction.
- Such tilting can take place at about six inversions or full swings per minute for approximately two minutes. The number of tilt cycles can be
- FIGURES 10 through 14 details of the process of the present invention and operation of the sedimentation apparatus 120 canbemore fully described.
- FIGURE 10 schematically illustrates specimen tube 121 immediately after obtaining a specimen of whole blood and removal of needle 159.
- Container 121 a 110 millimeter long tube with a 6 millimeter internal diameter bore and a 4 millimeter diameter rod in it, is filled with whole blood and diluent 171, as well as an air bubble 157, which represents the air left in the incompletely evacuated specimen tube.
- Specimen tube 121 is placed in tube orienting apparatus 123 in one of the grooves or troughs 137 in tray 136. The technician then can turn on the orientation device 123 by switching switch 140 to start the mixing process.
- Mixer light 142 will come "on” and the specimen tube is tilted about axle 139 above and below the horizon by about 70 degrees, as schematically illustrated in FIGURE 11.
- Bubble 157 migrates through specimen 171 along the member 152 as the liquid specimen passes beyond the bubble in the crescents created by the rod 152 positioned in bore 151 of tube 121.
- the mixing process is continued at six inversions per minute for approximately 2 minutes, at which time controller 141 for the mixer brings tube supporting tray 136 to a horizontal stationary position and turns off mixing light 142. It may be necessary for controller 141 to slow the rate of tilting or even stop at the extremes of the cycle to allow effective mixing, particularly of contents proximate the tube ends.
- the technician then lifts tube 121 from tray 136 and places the same in one of the notches 127 of centrifuge head 126.
- the operator turns the centrifuge "on,” using actuator button 131, and the tube will be spun about a spin axis 172, as schematically illustrated in FIGURE 12.
- the spin rate will typically be 400 rpm at a radius 173 of 4 centimeters. Centrifugation continues for approximately 20 seconds, which will cause a layer of rouleaux, schematically illustrated at 174, to form along the outermost side 160 of tube bore 151.
- Bubble 157 will be present at the top of the tube, and the tube will be oriented in centrifuge head 126 with the rod 152 closest to spin axis 172 so that the rouleaux will be induced to form and collect against the tube wall farthest from rod member 152.
- the technician will remove specimen tube 121 from centrifuge 126 and place the same in troughs 137 of tube orienting assembly 123, namely, in a near horizontal orientation as shown in FIGURE 13.
- Some upward tilt is advantageous in that it ensures that air bubble 157 will be located just under the stopper.
- FIGURE 13A shows the specimen in tube 121 at the start of gravity settling.
- Rouleaux 174 can be seen to be collected proximate the uppermost side 160 of the tube and the remainder of the specimen 177 is comprised of a mixture of erythrocytes and plasma in suspension.
- the centrifugation step has created sufficient rouleaux that upon placement of the tube in the horizontal position on tray 136 rouleaux will begin to settle or gravitate downwardly through mixture 177 of plasma and red blood cells.
- additional erythrocytes adhere to the falling clusters and additional rouleaux are formed.
- the specimen will have the appearance as schematically illustrated in FIGURE 13B.
- the bottom of the crescents of lumen 154 will be filled with sedimented erythrocytes, largely in rouleaux 174.
- a middle area of the specimen will contain a mixture 177 of plasma and erythrocytes in which rouleaux are less densely packed.
- a layer of plasma 178 will be present proximate uppermost side 160 of specimen tube 121.
- a separation boundary 179 also will be present between plasma 178 and the remainder of the specimen including erythrocytes.
- the final step in the method of the present invention is to measure the amount of settling which has occurred during the gravity settling period. This can be theoretically accomplished by measuring the location of separation boundary 179 while the specimen tube is still horizontally oriented. As a practical matter, however, determination of the precise quantity of settling is less accurate when specimen tube is horizontally oriented. Thus, it is preferable that the step of determining the amount of settling be accomplished by reorienting the specimen tube to the position shown in FIGURE 14, namely a near vertical orientation. Such reorientation is accomplished automatically after 3.5 minutes of gravity settling by controller 141, which smoothly and gradually tilts tray member 136 to a near vertical position, for example, to 80 degrees above the horizon.
- the rouleaux layer 174 sinks to the bottom end of the tube as does the mixture layer 177, while the lighter plasma layer 178 gravitates to the top and comes to rest just under bubble 157.
- the position of separation boundary 179 can now be measured by comparing the same to a measuring scale 138 on tray 136, or as shown in FIGURE 13, a measuring scale 138a on specimen 1990
- the entire process, as above described, can be accomplished in less than 5 minutes.
- the quantity of sedimentation which has occurred can be linearly related to Westergren sedimentation units by simply multiplying the sedimentation result in millimeters of fall by a linearmultiplier.
- extremelyhigh correlationwith Westergren data can be obtained using the apparatus of FIGURE 7 and a multiplier of 1.88.
- Correlation using a 1.88 times the measured sedimentation values using the FIGURE 7 apparatus and Westergren sedimentation values from specimens from the same patient have been found to have a Pearson correlation coefficient, r, value of approximately 0.99 and r 2 value of 0.95, which is an extremely high correlation.
- the same specimen can be tested again using the present process by simply turning on the mixer after the sedimentation has been measured to re-mix and re-suspend the erythrocytes. The process is then run again until a new sedimentationvalue is measured. Repeated runs on the same specimen allow an average value to be used. In 20-30 minutes, therefore, the same specimen can be tested three times to produce a highly accurate Westergren sedimentation rate.
- FIGURES 15 and 16 illustrate the high correlation of the sedimentation process of the present invention usingthe apparatus of FIGURE 7 with the Westergren process.
- SSR Speedy Sedimentation Rate
- ESR Electronic Stemcell Sedimentation Rate
- FIGURE 15 is based upon blood specimens from patients known to have disease or inflammatory conditions.
- FIGURE 16 is based upon blood specimens taken from healthy patients, which specimens were modified, as is well known in the art, by the addition of various amounts of gelatin and/or saline solution to increase the sedimentation rate of the specimen to simulate the sedimentation rates which would occur when a disease or inflammatory condition is present.
- FIGURES 15 and 16 the same blood specimen from a single patient was divided into two sub-specimens and sedimentation was measured with one sub-specimen using the Westergren process and the other sub-specimen using the present process.
- a centrifugation of 400 rpm on a 4 centimeter radius for a time period of 20 seconds and a gravity settling time of 3.5 minutes was used in each case.
- the SSR data was compared to the ESR data and a multiplier of 1.88 was used in both FIGURES 15 and 16 with the SSR data, based upon a "best fit" analysis of the SSR data to the line of identity.
- each data point represents two sedimentation rate measurements.
- Data point 91 on FIGURE 15, for example, is a SSR measurement times 1.88 which yielded a sedimentation value of 26 millimeters while the Westergren ESR value for the same patient was 29 millimeters.
- Data point 92 is a SSR x 1.88 value of 48 millimeters and a Westergren ESR of 39 millimeters.
- FIGURE 17 illustrates an apparatus suitable for use with this embodiment of the present process.
- a specimen tube 221 is provided which includes an elongated lumen 222 having an elongated member 223 mountedtherein.
- Member 223, however, is a ferromagnetic member, such as a glass or plastic tube 224 having a ferromagnetic material 226 inserted therein and end seals 227.
- Mounted proximate tube 221 is an electromagnet device 228, and the specimen tube 221 is supported on horizontal surface 229, although stopper 231 provides a slight inclination so that bubble 232 is proximate the stopper end of the specimen tube.
- the specimen 233 is first thoroughly mixed, for example by tilting or rotating tube 221 about a horizontal axis to cause bubble 232 to migrate from one end of the tube to the other.
- the ferromagnetic rod is fixed to one wall and, if not, ferromagnetic rod 223 is free to translate from side to side inside lumen 222.
- mixing tube 221 is placed on surface 229 and the electromagnet energized to pull member 223 to the upper side 235 of lumen 222.
- the rod is held against upper side 235 for 20 seconds, and it is believed that during that time period rouleaux begin forming in the horn regions between the rod and tube. If this techniquewere used alone, however, rouleaux formation would still be undesirably slow.
- electromagnet 228 is turned off and ferromagnetic rod 223 drops from upper side 235 of the tube lumen to the lower side 240 of lumen 222.
- the rod motion has a stirring or mixing effect, but it is hypothesizedthatthismotionof rod223 through specimen 233 is sufficient to create further rouleaux and effectively start the decantation phase.
- the specimen can be slowly raised to a vertical position and sedimentation measured.
- erythrocytes will remain in suspension in the plasma to a degree giving the plasma a cloudy appearance. This may be the result of the rod's motion through the specimen. Nevertheless, with strong backlighting the plasma/erythrocyte interface can still be located and the sedimentation rate determined. It is believed that location of the interface may be most accurately determinedbyusing automated optical readingapparatus.
- the preferred time period for the gravity settling step in a 6 millimeter by 100 millimeter tube with a 4 millimeter rod insert member is between about 2 to about 6 minutes.
- centrifuge time will effect results significantly. As the time is increased, more rouleaux than would be formed during the lag phase will be formed. Settling would accordinglybe too rapidor cause the sedimentation multiplication factor to change. A maximum of about 45 seconds of centrifugation can be tolerated, but 20 to 30 seconds at 5-10 g's is preferred. As the spin radius and spin rate are changed, the centrifugal force also will be varied, which will increase or decrease the amount of rouleaux formation.
- the rate of the reorientation step to enable measurement is not sensitive in the thin veil embodiment and only slightly more sensitive in the centrifugation and magnetic rod embodiments. If it is too fast, mixing can occur and if it is too slow, additional settling occurs. Reorientation in the range of about 2 to 4 seconds is permissible for the thin veil embodiment and in about 15 to 45 seconds for the centrifugation and magnetic rod embodiments produces substantially the same results, with 20 seconds being preferred.
- the sedimentation measurement can be made almost immediately, for example, within 5 seconds. Waiting too longwill have some effect on the correlation of data, even though the specimen hematocrit will be high as the specimen will be in the final or syneresis phase. The effect of waiting too long to measure can be significant because of the continual slumping of erythrocytes.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU28726/95A AU697731B2 (en) | 1994-07-12 | 1995-06-26 | Rapid determination of blood sedimentation rate |
EP95924076A EP0770207A4 (en) | 1994-07-12 | 1995-06-26 | Rapid determination of blood sedimentation rate |
NZ289006A NZ289006A (en) | 1994-07-12 | 1995-06-26 | Specimen container with a lumen portion having walls close together to prevent entry of a mixing bubble |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/270,681 | 1994-07-12 | ||
US08/270,681 US5594164A (en) | 1994-07-12 | 1994-07-12 | Method and apparatus for rapid determination of blood sedimentation rate |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996001990A1 true WO1996001990A1 (en) | 1996-01-25 |
Family
ID=23032342
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1995/008103 WO1996001990A1 (en) | 1994-07-12 | 1995-06-26 | Rapid determination of blood sedimentation rate |
Country Status (6)
Country | Link |
---|---|
US (4) | US5594164A (en) |
EP (1) | EP0770207A4 (en) |
AU (1) | AU697731B2 (en) |
CA (1) | CA2194870A1 (en) |
NZ (1) | NZ289006A (en) |
WO (1) | WO1996001990A1 (en) |
Families Citing this family (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5594164A (en) * | 1994-07-12 | 1997-01-14 | Bull; Brian S. | Method and apparatus for rapid determination of blood sedimentation rate |
US6506606B1 (en) * | 1995-06-06 | 2003-01-14 | Brigham And Women's Hospital | Method and apparatus for determining erythrocyte sedimentation rate and hematocrit |
ES2151939T3 (en) * | 1995-07-21 | 2001-01-16 | Becton Dickinson Co | METHOD AND APPLIANCE TO DETERMINE THE RATE OF SEDIMENTATION OF Erythrocytes. |
DE69515858T2 (en) * | 1995-07-21 | 2000-07-20 | Becton Dickinson Co | Sample tube for blood sedimentation determination and a detergent for use therein |
IT1286631B1 (en) * | 1996-05-16 | 1998-07-15 | Diesse Diagnostica | EQUIPMENT FOR THE PREPARATION AND DETERMINATION OF THE TESTS OF THE SPEED OF SEDIMENTATION OF ORGANIC LIQUIDS AND MORE |
US5914272A (en) * | 1996-06-19 | 1999-06-22 | Becton Dickinson And Company | Test method for determining the erythrocyte sedimentation rate and a surfactant for use therein |
US5731512A (en) * | 1996-09-16 | 1998-03-24 | Lewy, Deceased; Henry | Method for quick estimation of erythrocyte sedimentation rate with capillary tubes lined with preformed anticoagulant, mounted in an oblique position, and supported on a specially designed stand |
US6235536B1 (en) * | 1998-03-07 | 2001-05-22 | Robert A. Levine | Analysis of quiescent anticoagulated whole blood samples |
JP2000329779A (en) * | 1999-05-19 | 2000-11-30 | Sefa Technology Kk | Sedimentation speed measuring method and its device |
US6204066B1 (en) * | 1999-06-25 | 2001-03-20 | Robert A. Levine | Rapid method for determining the erythrocyte sedimentation rate in a sample of anticoagulated whole blood |
US6422068B1 (en) * | 2000-09-29 | 2002-07-23 | General Electric Company | Test rig and particulate deposit and cleaning evaluation processes using the same |
WO2002087660A1 (en) * | 2001-04-26 | 2002-11-07 | Asahi Medical Co., Ltd. | Blood filtration methods and blood filtration apparatus |
US20060216829A1 (en) * | 2003-03-21 | 2006-09-28 | Denis Bouboulis | Erythrocyte sedimentation rate (ESR) test measurement instrument of unitary design and method of using the same |
US6974701B2 (en) * | 2003-03-21 | 2005-12-13 | Hemovations, Llc | Erythrocyte sedimentation rate (ESR) test measurement instrument of unitary design and method of using the same |
US20060133963A1 (en) * | 2004-12-16 | 2006-06-22 | Israel Stein | Adapter for attaching information to test tubes |
US20060157549A1 (en) * | 2005-01-14 | 2006-07-20 | Stein Israel M | Smart cards for automated sample analysis devices |
US20060233676A1 (en) * | 2005-04-13 | 2006-10-19 | Stein Israel M | Glass test tube having protective outer shield |
DE102005048236A1 (en) * | 2005-10-07 | 2007-04-12 | Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg | Apparatus and method for determining the volume fractions of the phases in a suspension |
US7731414B2 (en) * | 2007-02-08 | 2010-06-08 | Instrumentation Laboratory Company | Reagent cartridge mixing tube |
US8728413B2 (en) * | 2007-02-08 | 2014-05-20 | Biokit, S.A. | Reagent container pack |
SE531510C2 (en) * | 2007-09-04 | 2009-05-05 | Tommy Forsell | blood Analysis |
US8667832B2 (en) * | 2008-03-04 | 2014-03-11 | Cleveland State University | Method and system for particle settling velocity measurement |
JP5484849B2 (en) * | 2009-09-30 | 2014-05-07 | シスメックス株式会社 | Blood sample processing apparatus and blood sample processing method |
AU2013292378A1 (en) * | 2012-07-18 | 2015-01-29 | Theranos Ip Company, Llc | Rapid measurement of formed blood component sedimentation rate from small sample volumes |
BR112015002561A2 (en) * | 2012-08-08 | 2018-05-22 | Koninklijke Philips Nv | system for separation of a heterogeneous analyte, and method for separation of a heterogeneous analyte. |
CN103245606B (en) * | 2013-05-07 | 2014-10-22 | 山东慧敏科技开发有限公司 | Device for measuring suspension property of turbid liquid, and method for testing suspension property of turbid liquid by centroid method |
US11378435B2 (en) * | 2014-09-17 | 2022-07-05 | Quest Diagnostics Investments Incorporated | Device and method for evaluating amount of biological sample in a specimen container |
US11291931B2 (en) | 2014-12-15 | 2022-04-05 | Akadeum Life Sciences, Inc. | Method and system for buoyant separation |
WO2016100290A1 (en) * | 2014-12-15 | 2016-06-23 | Akadeum Life Sciences, LLC | Method and system for buoyant separation |
FR3040891B1 (en) * | 2015-09-14 | 2019-05-31 | Olivier Charansonney | DEVICE FOR DISAGGREGATING A COMPLEX MEDIUM |
US11618031B2 (en) * | 2016-11-18 | 2023-04-04 | North Carolina State University | Multi-sample chamber for extended term microscope imaging |
JP7189314B2 (en) | 2018-07-09 | 2022-12-13 | アカデューム ライフ サイエンセズ,インコーポレイテッド | Systems and methods for handling airborne particles |
CN113369363B (en) * | 2021-06-22 | 2022-07-08 | 中山市莱利灯饰股份有限公司 | Lamps and lanterns production and processing equipment |
WO2023028329A1 (en) | 2021-08-26 | 2023-03-02 | Akadeum Life Sciences, Inc. | Method and system for buoyant separation |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3824841A (en) * | 1971-02-08 | 1974-07-23 | Coulter Electronics | Method for sedimentation study |
US4278437A (en) * | 1979-04-09 | 1981-07-14 | Jan Haggar | Fluid specimen holder for biological fluid testing |
US4474056A (en) * | 1981-08-18 | 1984-10-02 | University Of Victoria | Erythrocyte settling rate meter |
US4701305A (en) * | 1985-09-06 | 1987-10-20 | Nissho Corporation | Device for sampling blood and measuring erythrocyte sedimentation rate |
US4848900A (en) * | 1987-06-22 | 1989-07-18 | Kuo Cheng Deng | Computerized automatic monitoring and recording system of erythrocyte sedimentation process |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1244025A (en) * | 1913-08-16 | 1917-10-23 | Charles Browning Jr | Viscometer. |
US1247523A (en) * | 1913-08-29 | 1917-11-20 | Tinius Olsen Testing Mach Co | Method and machine for determining viscosity. |
US1480849A (en) * | 1922-03-22 | 1924-01-15 | Ralph G Adams | Lubricating-oil dispenser |
US2431378A (en) * | 1944-04-15 | 1947-11-25 | Eitzen | Viscosimeter |
US2609682A (en) * | 1948-12-18 | 1952-09-09 | Louis C Eitzen | Viscosity meter air barrier |
US3631847A (en) * | 1966-03-04 | 1972-01-04 | James C Hobbs | Method and apparatus for injecting fluid into the vascular system |
US3525253A (en) * | 1968-03-21 | 1970-08-25 | Monsanto Co | Arresting elements for viscometers |
CH475793A (en) * | 1969-01-22 | 1969-07-31 | Greiner Electronic Ag | Sample tube |
US3533229A (en) * | 1969-05-26 | 1970-10-13 | Jon L Liljequist | Tilting timers |
US3660037A (en) * | 1970-08-10 | 1972-05-02 | Kurt Rudolf Sokol | Device for measuring blood sedimentation rate |
US3854324A (en) * | 1971-10-27 | 1974-12-17 | T Altshuler | Blood clotting time and strength measuring system |
US3914985A (en) * | 1974-03-29 | 1975-10-28 | American Hospital Supply Corp | Centrifuging device and method |
US3888239A (en) * | 1974-06-21 | 1975-06-10 | Morton K Rubinstein | Fluid injection system |
US4041502A (en) * | 1975-12-22 | 1977-08-09 | Williams Tool, Inc. | Sedimentation recorder |
US4027660A (en) * | 1976-04-02 | 1977-06-07 | Wardlaw Stephen C | Material layer volume determination |
US4221324A (en) * | 1977-12-05 | 1980-09-09 | Raymond Frey | Centrifuge with variable angle of attack |
US4214874A (en) * | 1979-02-08 | 1980-07-29 | American Hospital Supply Corporation | Combination and method for mixing the contents of a blood collection tube and thereafter removing the mixing element |
US4472357A (en) * | 1981-11-18 | 1984-09-18 | Medical Laboratory Automation, Inc. | Blood bank cuvette cassette and label therefor |
IT1192490B (en) * | 1982-08-10 | 1988-04-13 | Diesse Diagnostica Senese Srl | APPARATUS FOR THE DETERMINATION OF THE SPEED OF ERITROSEDIMENTATION OF THE BLOOD (ESR) ON A MULTIPLE OF SAMPLES |
US4599219A (en) * | 1982-10-15 | 1986-07-08 | Hemotec, Inc. | Coagulation detection by plunger sensing technique |
US4517830A (en) * | 1982-12-20 | 1985-05-21 | Gunn Damon M | Blood viscosity instrument |
US4579828A (en) * | 1983-12-15 | 1986-04-01 | Becton, Dickinson And Company | Clot activator for serum separation tubes |
GB2166977B (en) * | 1984-11-08 | 1988-04-20 | Mitsubishi Monsanto Chem | Medical material and process for its production |
US4567754A (en) * | 1985-03-29 | 1986-02-04 | Wardlaw Stephen C | Measurement of small heavy constituent layer in stratified mixture |
JPH0687062B2 (en) * | 1985-05-10 | 1994-11-02 | 株式会社京都医科学研究所 | How to prevent glycolysis in blood |
US4765179A (en) * | 1985-09-09 | 1988-08-23 | Solid State Farms, Inc. | Radio frequency spectroscopy apparatus and method using multiple frequency waveforms |
US4873872A (en) * | 1988-01-25 | 1989-10-17 | Wechsler Lawrence I | Float for fluid measurements |
US5030421A (en) * | 1988-08-31 | 1991-07-09 | Davstar Industries, Inc. | Integral centrifuge tube and specimen slide |
IT1233510B (en) * | 1989-04-05 | 1992-04-03 | Diesse Diagnostica | APPARATUS FOR THE PREPARATION AND DETERMINATION OF THE SEDIMENTATION SPEED EXAMINATIONS OF ORGANIC LIQUIDS AND OTHER |
US5328822A (en) * | 1990-04-23 | 1994-07-12 | Solid State Farms, Inc. | Apparatus and method for sedimentation based blood analysis |
US5275953A (en) * | 1991-04-22 | 1994-01-04 | Bull Brian S | Apparatus and method for in vitro manipulation of blood |
US5154082A (en) * | 1991-05-20 | 1992-10-13 | International Technidyne Corporation | Microprocessor-controlled apparatus and method for detecting the coagulation of blood |
CA2067695C (en) * | 1991-06-06 | 1997-07-08 | James A. Burns | Blood microcollection tube assembly |
US5232828A (en) * | 1992-03-09 | 1993-08-03 | Becton, Dickinson And Company | Coating agents for cell recovery |
US5273765B1 (en) * | 1993-02-10 | 1996-05-28 | Ese Inc | Initiating a response signal to a predetermined processing condition |
US5594164A (en) * | 1994-07-12 | 1997-01-14 | Bull; Brian S. | Method and apparatus for rapid determination of blood sedimentation rate |
US5714125A (en) * | 1996-03-07 | 1998-02-03 | Medical Safety Products, Inc. | Device for collecting a blood sample from a plastic segment tube |
-
1994
- 1994-07-12 US US08/270,681 patent/US5594164A/en not_active Expired - Fee Related
-
1995
- 1995-06-26 CA CA002194870A patent/CA2194870A1/en not_active Abandoned
- 1995-06-26 EP EP95924076A patent/EP0770207A4/en not_active Withdrawn
- 1995-06-26 NZ NZ289006A patent/NZ289006A/en unknown
- 1995-06-26 AU AU28726/95A patent/AU697731B2/en not_active Ceased
- 1995-06-26 WO PCT/US1995/008103 patent/WO1996001990A1/en not_active Application Discontinuation
-
1996
- 1996-09-17 US US08/718,637 patent/US5731513A/en not_active Expired - Fee Related
-
1997
- 1997-07-28 US US08/901,593 patent/US5844128A/en not_active Expired - Fee Related
-
1998
- 1998-11-30 US US09/201,321 patent/US6098451A/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3824841A (en) * | 1971-02-08 | 1974-07-23 | Coulter Electronics | Method for sedimentation study |
US4278437A (en) * | 1979-04-09 | 1981-07-14 | Jan Haggar | Fluid specimen holder for biological fluid testing |
US4474056A (en) * | 1981-08-18 | 1984-10-02 | University Of Victoria | Erythrocyte settling rate meter |
US4701305A (en) * | 1985-09-06 | 1987-10-20 | Nissho Corporation | Device for sampling blood and measuring erythrocyte sedimentation rate |
US4848900A (en) * | 1987-06-22 | 1989-07-18 | Kuo Cheng Deng | Computerized automatic monitoring and recording system of erythrocyte sedimentation process |
Non-Patent Citations (1)
Title |
---|
See also references of EP0770207A4 * |
Also Published As
Publication number | Publication date |
---|---|
AU2872695A (en) | 1996-02-09 |
CA2194870A1 (en) | 1996-01-25 |
US5594164A (en) | 1997-01-14 |
EP0770207A1 (en) | 1997-05-02 |
EP0770207A4 (en) | 1999-10-13 |
AU697731B2 (en) | 1998-10-15 |
US5731513A (en) | 1998-03-24 |
US5844128A (en) | 1998-12-01 |
NZ289006A (en) | 1998-08-26 |
US6098451A (en) | 2000-08-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5594164A (en) | Method and apparatus for rapid determination of blood sedimentation rate | |
US6153148A (en) | Centrifugal hematology disposable | |
JP4763794B2 (en) | Apparatus and means for measuring phase volume fraction in suspension | |
US5650068A (en) | Column agglutination assay and device using biphasic centrifugation | |
US4698311A (en) | Particle washing and separation method | |
EP0830581B1 (en) | Determining erythrocyte sedimentation rate and hematocrit | |
US4148607A (en) | Apparatus and analysis for agglutination reaction | |
Sharpe | Methods of cell separation | |
JP3547894B2 (en) | Method and apparatus for determining blood sedimentation velocity | |
JP6552597B2 (en) | Microplate | |
EP0350851A1 (en) | Method and apparatus for separating mononuclear cells from blood | |
JP6263258B2 (en) | Method for determining the result of an agglutination reaction and test apparatus comprising a control unit for carrying out the method | |
Miller | [8] Separation of cells by velocity sedimentation | |
US4137755A (en) | Material layer volume determination | |
US4201470A (en) | Method and apparatus for measurement and registration of the aggregation rate of particles suspended in a liquid | |
EP0396115A2 (en) | Method of forming agglutinates in blood samples | |
CA1198970A (en) | Apparatus to evaluate the "erythrayte sedimentation rate" (esr) in several samples | |
Anderson | Analytical techniques for cell fractions: VIII. Analytical differential centrifugation in angle-head rotors | |
DE60110951T2 (en) | centrifugation container | |
JPH102900A (en) | Method for detecting analyte in sample liquid, reagent kit and reaction vessel | |
US3844662A (en) | Sedimentation instrument for body fluids and method of microscopic examination of the sediment | |
US4563332A (en) | Liquid sampling apparatus with retention means | |
Hughes et al. | A method for determining the differential sedimentation of proteins in the high speed concentration centrifuge | |
US4693984A (en) | Method and apparatus for sequential fractionation | |
Bull et al. | Is the packed cell volume (PCV) reliable? |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AM AT AU BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU IS JP KE KG KP KR KZ LK LR LT LU LV MD MG MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TT UA UG UZ VN |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): KE MW SD SZ UG AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2194870 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 289006 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1995924076 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 1995924076 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1995924076 Country of ref document: EP |