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Patent 2241246 Summary

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(12) Patent: (11) CA 2241246
(54) English Title: RED BLOOD CELL SPILLOVER DETECTION TECHNIQUE
(54) French Title: TECHNIQUE DE DETECTION DU DEBORDEMENT DES GLOBULES ROUGES
Status: Deemed expired
Bibliographic Data
(51) International Patent Classification (IPC):
  • G01N 15/06 (2006.01)
  • A61M 1/36 (2006.01)
  • G01N 21/55 (2014.01)
(72) Inventors :
  • GIBBS, BRUCE W. (United States of America)
(73) Owners :
  • CARIDIANBCT, INC. (United States of America)
(71) Applicants :
  • COBE LABORATORIES, INC. (United States of America)
(74) Agent: ROBIC
(74) Associate agent:
(45) Issued: 2006-04-11
(86) PCT Filing Date: 1997-11-04
(87) Open to Public Inspection: 1998-05-14
Examination requested: 2001-07-03
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): Yes
(86) PCT Filing Number: PCT/US1997/020086
(87) International Publication Number: WO1998/020345
(85) National Entry: 1998-06-29

(30) Application Priority Data:
Application No. Country/Territory Date
08/746,109 United States of America 1996-11-06

Abstracts

English Abstract



An apparatus and
a method are provided
to monitor a generally
transparent blood tube at a
location that is downstream
from a blood separator in
order to detect the presence
of red blood cells in a tube
that is intended to carry a
different blood component,
for example platelets. A
red light source and a green
light source are located
id relation to the tube so
that red light emission and
green light emission are
directed toward the tube
and toward the flowing
blood component(s) that is
carried within the tube. The
red light source produces
a red reflection intensity
from red blood cells whose
magnitude increases as a
function of an increase in
the concentration of red
blood cells. The green light
source produces a green
reflection intensity from the red blood cells whose magnitude decreases as a
function of an increase in the concentration of the red blood
cells. These two light reflections are sensed by means of one broadband
photodetector, or by two band-specific photodetectors, that are
located on the same side of the tube, so as to be responsive only to reflected
light. An output is provided by detecting the ratio of the
magnitude of the red reflection intensity to the magnitude of the green
reflection intensity.


French Abstract

L'invention porte sur un appareil et un procédé de surveillance d'un tube de sang généralement transparent se trouvant en aval d'un séparateur sanguin de façon à détecter la présence de globules rouges dans un tube destiné à transporter un composant sanguin différent tel que des plaquettes. Une source de lumière rouge et une source de lumière verte sont placées en relation avec le tube de sorte que l'émission de lumière rouge et l'émission de lumière verte soient dirigées vers le tube et vers le(s) composant(s) sanguin(s) s'écoulant et s'acheminant vers le tube. La source de lumière rouge génère une intensité de réflexion rouge émanant des globules rouges dont la grandeur est proportionnelle à la concentration des globules rouges. La source de lumière verte génère une intensité de réflexion verte émanant des globules rouges dont la grandeur est inversement proportionnelle à la concentration des globules rouges. Ces deux réflexions lumineuses sont détectées au moyen d'un photodétecteur large bande, ou par deux photodétecteurs à spécificité de bande qui sont placés sur le même côté du tube de sorte qu'ils réagissent uniquement à la lumière réfléchie. Il en résulte une sortie qui détecte le rapport de la grandeur de l'intensité de lumière rouge à la grandeur de l'intensité de lumière verte.

Claims

Note: Claims are shown in the official language in which they were submitted.




WHAT IS CLAIMED IS:
1. Apparatus (24) for monitoring a light transparent
tube (22) adapted to carry flow of a first blood component
and for detecting the undesirable presence or spillover of
a second blood component into the tube flow, the apparatus
(24) comprising:
a first (54) and a second (53) light source physically
located in relation to a side of the tube (22) so that
light emission from said first light source (54) and from
said second light source (53) are directed toward said side
of the tube (24), said first light source (54) having a
first wavelength that is selected to produce a first light
reflection intensity from any second blood component
present in the tube flow, the first light reflection
intensity increasing as a function of an increase in
concentration of the second blood component in the tube
flow, and said second light source (53) having a second
wavelength that is selected to produce a second light
reflection intensity from any second blood component
present in the tube flow, the second light intensity
decreasing as a function of an increase in the
concentration of the second blood component in the tube
flow;
a light intensity responsive photosensor (56)
producing a first signal proportional to said first light
reflection intensity and a second signal proportional to
said second light reflection intensity; and
a comparator (33) receiving said first and second
signals from said photosensor and producing a ratio
measurement proportional to said first signal as a
numerator and said second signal as a denominator.
2. The apparatus of claim 1, wherein said first and
second light sources are pulse energized during a first
time interval and a second time interval, respectively,
21


said photosensor operates to detect said first reflection
intensity during said first time interval and to detect
said second reflection intensity during said second time
interval.
3. The apparatus of claim 1, wherein the second blood
component is red blood cells, wherein said first light
source is a red light source, and wherein said second light
source is a green light source.
4. The apparatus of claim 3, wherein said comparator
detects a ratio of said first light reflection intensity to
said second light reflection intensity.
5. The apparatus of claim 4, wherein the first blood
component comprises platelets.
6. The apparatus of claim 5, wherein said first light
source and said second light source are energized during a
first time interval and a second time interval, respec-
tively, wherein said photosensor operates to detect said
first light reflection intensity during said first time
interval and to detect said second light reflection
intensity during said second time interval, and wherein
said first light source and said second light source are
pulse energized.
7. The apparatus of claim 1, wherein said first light
source, said second light source and said photosensor are
all physically located adjacent to same side of the tube,
to thereby facilitate the physical loading of the tube onto
the apparatus.
8. The apparatus of claim 7, wherein said comparator
detects a ratio of said first light reflection intensity to
said second light reflection intensity.
22



9. A method of monitoring a non-red blood cell tube and
detecting the quantity of red blood cells flowing in the
tube, comprising the steps of:
directing red light toward and from a side of the
tube;
directing green light toward and from a side of the
tube;
detecting a red light reflection intensity from said
side of the tube, and from red blood cells that may be
within the tube;
detecting a green light reflection intensity from said
side of said tube, and from red blood cells that may be
within the tube;
providing an output by detecting a ratio of said red
light reflection intensity to said green light reflection
intensity; and
using the output to detect the quantity of red blood
cells that is flowing in the tube.
10. The method of claim 9, wherein said step of
providing an output includes the steps of;
providing a threshold value, and
comparing said ratio to said threshold value.
11. The method of claim 9, wherein said step of
directing said red light toward the tube and said step of
detecting said red light reflection intensity occur during
a first time interval, and wherein said step of directing
said green light toward the tube and said step of detecting
said green light reflection intensity occur during a second
time interval that is different than said first time
interval.
23


12. The method of claim 11, wherein said step of
providing an output includes steps of:
providing a threshold value, and
comparing said ratio to said threshold value.
13. The method of claim 9, wherein said side of the
tube toward which red light is directed, and said side of
the tube toward which green light is directed, comprise a
common side of the tube.
14. The method of claim 9, wherein said side of the
tube toward which red light is directed, and said side of
the tube toward which green light is directed, comprise
opposite sides of the tube.
15. A method sensing red blood cell spillover into a
non-red blood cell tube, comprising the steps of:
providing a light transparent empty tube;
providing a photosensor to view an external portion of one side
of said tube;
determining a first output of said photosensor when said
photosensor views said external portion of said empty tube;
providing a red light source that is located to illuminate said
external portion of said one side of said tube with red light when said red
light
source is energized;
providing a green light source that is located to illuminate said
external portion of said one side of said tube with green light when said
green
light source is energized;
determining a second output of said photosensor while said
photosensor views said external portion of said empty tube, and while only
said red light source is energized;
24


determining a third output of said photosensor while said
photosensor views said external portion of said empty tube, and white only
said green light source is energized;
establishing a compensated red photosensor output by
subtracting said first output from said second output;
establishing a compensated green photosensor output by
subtracting said first output from said third output;
providing ratio determining means;
initializing said ratio determining means by
utilizing said ratio determining means to set a ratio of
said compensated red photosensor output to said compensated
green photosensor output equal to one;
filling said tube with a non-red blood cell sample that is normally
devoid of red blood cells;
energizing only said green light source, to thereby direct green
light toward said external portion of said filled tube;
determining a fourth output of said photosensor as said
photosensor views green light that is reflected from said non-red blood
sample within said filled tube while only said green light source is
energized;
energizing only said red fight source, to thereby direct red light
toward said external portion of said filled tube;
determining a fifth output of said photosensor as said
photosensor views red light that is reflected from said non-red blood sample
within said filled tube while only said red light source is energized; and
utilizing said initialized ratio determining means to provide a red
blood cell spillover output as a function of a ratio of said fifth output and
said
fourth output.
16. Apparatus for continuously monitoring the flow of
an non-red blood cell blood component for the occurrence of
a spillover or red blood cells, comprising:




a generally elongated and light transparent tube for carrying the
flow of a non-red blood cell blood component, said tube having a generally
elongated tube axis;
a red light source located to one side of the tube and positioned
to direct a beam of red light at an angle of about 45 degrees to said tube
axis,
and toward an external portion of said one side of the tube, when said red
light source is energized;
a green light source located to said one side of the tube and
positioned to direct a beam of green light at an angle of about 45 degrees to
said tube axis, and toward said external portion of said one side of the tube
when said red Light source is energized;
a photodetector that is responsive to red light reflection and to
green fight reflection, said photodetector being located to said one side of
the
tube and positioned to view said external portion of said one side of the tube
along a view axis that extends generally normal to said tube axis;
energizing means for alternately pulse energizing said red light
source during a first time interval and said green light source during a
second
time interval;
ratio determining means responsive to a red light reflection
output from said photodetector during said first time interval, and to a green
light reflection output from said photodetector during said second time
interval; and
red blood spillover output means controlled by said ratio
determining means as a function of a ratio of said red light reflection output
to
said green light reflection output.
17. The apparatus of claim 16, wherein said
energizing means provides generally equal time periods of
pulse energizing of said red light source and said green
light source.
26



18. The apparatus of claim 17, wherein said red light
source and said green light source comprise light emitting
diodes.
19. The apparatus of claim 18, wherein said light
emitting diodes are energized at a frequency of about
2 Khz.
20. The apparatus of claim 19, wherein the tube is a
component of a disposable set and wherein the photosensor
is further operable to detect a third reflection intensity
and a fourth reflection intensity before a blood component
is carried in said tube and to determine a configuration of
the disposable set based on said third and fourth
reflection intensities.
21. The method of claim 11, wherein the step of
providing an output by detecting a ratio further comprises
applying said red light reflection intensity as a numerator
and said green light intensity as a denominator to produce
a ratio measurement, and wherein the step of using the
output to detect the quantity of red blood cells flowing in
said tube further comprises correlating said ratio
measurement to a hematocrit.
27

Description

Note: Descriptions are shown in the official language in which they were submitted.



CA 02241246 1998-06-29
WO 98/20345 PCT/fIS97/20086
RED BLOOD CELL SPILLOVER DETECTION TECHNIQUE
° Field Of The Invention
The present invention generally relates to the field of blood separation,
and specifically to the separation of whole human blood info its red blood
cell,
plasma and platelet components. More particularly, the present invention
relates to the detection of an undesirable spiliover of red blood cells into a
blood component stream, for example a platelet stream, that should not
contain red blood cells.
Background Of The invention
Continuous blood separators are used to separate whole human blood
into its various components, such as platelets, red blood cells andlor plasma.
These components are removed from the separators in separate streams,
sometimes referred to as collect tubes. Normally, the collect tubes of the
blood separator are continuously monitored to detect the undesirable
occurrence of a spillover of one blood component into a collect tube intended
to carry a different blood component. For example, the spillover of red blood
cells into a collect tube intended to carry only platelets may be monitored.
A conventional technique by which undesirable spillover of red blood
cells is monitored is the measurement of a color index of a non-red blood cell
blood component that flows through a collect tube. This measurement is
taken at a point downstream of the blood separator. By using a green fight
source and measuring the optical density of the non-red blood cell blood
component, the total number of particles in the flowing non-red blood cell
blood component and the green light absorbence of the non-red blood cell
blood component can be monitored. An increase in green light absorbence in
SUBSTITUTE SHEET (RULE 26)


CA 02241246 1998-06-29
WO 98/20345 PCT/US97/20086
relation to optical density is then correlated to the occurrence of a red
blood
cell spillover.
This type of detection equipment typically requires a Eight source to be
physically positioned on one side of a collect tube and a photosensor located
on the opposite side of the collect tube. For this system to work in an
optically efficiently manner, the portion of the collect tube adjacent the
light
source must present a generally flat surface to the light source and the
photosensor. Relatively expensive schemes and custom containers have
been used to produce a flat interface to the light source and to the
photosensor, to thereby increase optical efficiency in this manner. For
example, collect tubes may be flattened.
Another problem experienced with such detection equipment is-that
measurement of optical density requires measurement of the intensity of light
that is received by the photosensor. Artifacts such as dirt particles that
affect
the light intensity received by the photosensor tend to provide a false
indication of red blood cell spillover. In addition, there remains a
continuous
need for a detector equipment capable of greater sensitivity in a sensitive
detection of red blood cell spillover.
The following United States patents are of general interest: U.S.
Patent No. 3,236,602 relates to a flow cell for the colorimetric examination
of
the light transmission characteristics of a liquid. U.S. Patent No. 3,527,542
relates to apparatus for measuring blood flow wherein a first beam of
monochromatic light passes through a cuvette to impinge on a first photocell
while a second light beam impinges on a second photocell. The two photocell
outputs are then compared. Reissue Patent No. 29,141 describes a slit cell
for use with optical particle sensors that operate on the principle of light
scattering or interception.
b
2
SUBSTITUTE SHEET (RULE 26)


CA 02241246 1998-06-29
WO 98/20345 PCT/US97/2Q086
Various patents identify light sources having particular wave lengths for
the measurement of liquid characteristics. U.S. Patent No. 4,227,814
describes an optical detector that is used with blood separating apparatus
wherein red blood cell spiilover is detected as a function of optical density.
Low power light (750 foot candles at a power consumption of 1 to 2 watts)
passes through the sample and a photodetector senses the optical density of
the sample. Blue-green light 550 nanometers (nm) wavelength and a type 9
CAD sulfide photodetector are used. U.S. Patent No. 4,229,179 describes
spectrophotometric measuring apparatus wherein the visible, UV or
IO fluorescent radiant energy that passes through a sample is detected. U.S.
Patent No. 4,444,498 describes the measurement of blood characteristics by
using blood reflected light provided by two intermittently operating light
sources having two different wavelengths {red and infra-red). Optical
feedback loops control the intensity of the two light sources. A flat-
bandwidth
sensor detects the two reflections of different wavelengths.
Also by way of example, U.S. Patent No. 4,810,090 describes the
sensing of platelet concentration, and the detection of red blood cell
spiliover
into the platelet flow, by using an infra-red-emitting LED {875 nm) and a
green-emitting LED (565 nm) that operate at different times. These two LEDs
emit fight along an axis that extends through the stream of platelet flow. A
first light sensor is placed on-axis and opposite the two light sources to
detect
light that passes on-axis and through the platelet stream. A second light
sensor is placed generally across from the two light sources, but is located
upstream of the first sensor, so as to measure light that is scattered off
axis
and upstream of the two fight sources. A third light sensor is placed
generally
across from the two light sources but is located downstream of the first
sensor, to measure light that is scattered off-axis and downstream of the
light
sources. Under abnormal conditions, for example, when clumping, air
bubbles, hemolysis, and spillovers of red blood cells or white blood
cells has occurred, a color-index and a scatter-index are calculated.
3
SUBSTITUTE SHEET (RULE 26~


CA 02241246 1998-06-29
WO 98/20345 PCT/ITS97/20086
Scattered light is also measured as a means of identifying blood
components in other U.S. patents. For example, U.S. Patent No. 4,522,494
describes an apparatus that determines the concentration of non-aggressive
platelets and the concentration of discs that are within a flexible bag, using
scattered laser light. U.S. Patent No. 4,577,964 relates to the use of
scattered light to discriminate platelets from red blood cells within a sample
volume. U.S. Patent 4,745,279 relates to the diffusion of infrared light by a
volume of blood in order to measure the hematocrit of a volume of blood.
This device may be used to measure oxygen saturation by the use of an LED
light emitter and a reflection detector that are located on the same side of
the
blood volume. U.S. Patent No. 5,372,136 describes a finger-clip/ear-lobe-clip
arrangement in which at least two wavelengths of light are passed through
body tissue and light transmission or reflection is detected by a
photodetector.
While the prior art as exemplified above is generally useful for its
limited intended purposes, the need remains for a construction and
arrangement that provides a more sensitive detection of red blood cell
spillover. In addition, there remains a need for equipment configuration
wherein collect tubing does not have to be of special flattened construction
manually between opposing transmitted and receiving devices.
SUMMARY OF THE INVENTION
The present invention provides a new, unusual and unobvious
construction and arrangement for monitoring the undesirable spillover of a
blood component in a tube intended to carry a different blood component.
The present invention is particularly adapted for continuously monitoring one
or more blood collect tubes at one or more locations downstream of a
continuous blood separator, to detect the undesirable spillover of one blood
component into a collect tube intended to carry a different blood component.
4
SUBSTITUTE SHEET (RULE 26)


CA 02241246 2004-09-20
In an embodiment of the invention, the undesirable
spillover of red blood cells into a tube intended to carry
platelets is continuously monitored.
According to the present invention, there is provided
an apparatus for monitoring a light transparent tube
adapted to carry flow of a first blood component and for
detecting the undesirable presence or spillover of a second
blood component into the tube flow, the apparatus
comprising:
a first and a second light source physically located
in relation to a side of the tube so that light emission
from said first light source and from said second light
source are directed toward said side of the tube, said
first light source having a first wavelength that is
selected to produce a first light reflection intensity from
any second blood component present in the tube flow, the
first light reflection intensity increasing as a function
of an increase in concentration of the second blood
component in the tube flow, and said second Light source
having a second wavelength that is selected to produce a
second light reflection intensity from any second blood
component present in the tube flow, the second light
intensity decreasing as a function of an increase in the
concentration of the second blood component in the tube
flow;
a light intensity responsive photosensor producing a
first signal proportional to said first light reflection
intensity and a second signal proportional to said second
light reflection intensity and
a comparator receiving said first and second signals
from said photosensor and producing a ratio measurement
5


CA 02241246 2004-09-20
proportional to said first signal as a numerator and said
second signal as a denominator.
!n accordance within its broader aspects; the present invention
provides two light sources having two different but related emission
wavelengths. The light outputs of these two light sources are directed toward
a tube intended to exclusively carry a first blood component. The two
different light wavelengths are selected such that (1) the first light source
has
a first wavelength which is reflected from a second blood component with an
intensity that increases with an increase in the concentration of the second
blood component, and (2) the second light source has a second wavelength
which is reflected from the second blood component with an intensity that
5a


CA 02241246 2001-11-16
decreases as a function of an increase in the concentration of the second
blood component.
Preferab~_y, in accordance with the present
invention, the intensity of the first light source's
reflection and the ini=ensity of the second light source's
reflection are both detected. This results in an intensity-
1 electrical signal that increases when the second blood
component concentration or density increases, and an
intensity-2 electrical signal that decreases when the
second blood component. concentration or density increases.
By electrically comparing the intensity-1 signal to the
intensity-2 signal, a.n arrangement is provided which is
very sensitive to the occurrence of spillover of the second
blood component into the tube intended to carry only the
first blood component. Preferably this comparison comprises
a ratio measurement. wh~~re:i_n i:he numerator increases and the
denominator decreases as the concentration of red blood
cells increases.
Preferably, i_n one embodiment of the present
invention, l~he secon:~ blood component comprises red blood
cells, the first lighi, source is a red light source, the
second light source is a green light source, and the
electrical comparisoru c>perates to detect the ratio of the
reflected red light a.ntensity to the reflected green light
intensity. :3ince an increase in the concentration of red
blood cells causes the numerator of this ratio to increase,
as the denominat=or of this ratio concomitantly decreases,
the resulting ratio si.gna:L is very sensitive to changes in
the concentration of red blood cells within the tube. For
example, this ratio changes markedly at hematocrit of lo,
0. 5 o and even below 0. '>'o, thus making the apparatus/method
6


CA 02241246 2001-11-16
of this invention more sensitive than prior detection of
red blood cell spillover.
Preferably, the light outputs of these two light
sources may be continuous, in which case the two light
reflections are simultaneously detected by the use of two
light specific detectors that are individually responsive
only to one of ~~he two wavelengths. Alternatively, the two
light sources are pulse-energized during two different time
intervals, and one or two light detectors are provided,
having a relatively wide wavelength response. Since the two
light reflections oc~cur during t:wo different time
intervals, interference between the two light reflections
is prevented.
Preferably, when the second blood component
includes another particular component, reflection of the
green and red light. form t=hat particular component is found
to be affected i.n a similar manner as the concentration or
density of the component changes.
Preferably, in an embodiment of the present
invention, each light source and its mating light detector
are physically mounted on the same side of the tube.
Preferably, the two light sources and the two detectors are
physically located oru t:he same side of the tube. In this
configuration the tube can be automatically loaded into the
apparatus of this invention, and set-up time and
manufacturing cost are mirnimized. Moreover, the
construction and arrangement of this invention does not
require the use of cuvettes, does not require that the tube
be flattened, is less prone tc: the false detection of red
blood cell spillover, locates the light emitters and the
light detectors on the same side of the tube, and provides
6a


CA 02241246 2001-11-16
for the optically ef1=ir_ient and sensitive detection of red
blood cell spillover.
According t<_> the present invention, there is
provided apparatus f<>r continuously monitoring the flow of
a non-red blood cell )'Mood component for the occurrence of
a spillover of red blood cells, comprising:
a generally elongated and light transparent tube for carrying the
flow of a non-red blood cell blood component, said tube having a generally
elongated tube axis;
l,~ a red light source located to one side of the tube and positioned
to direct a beam of red light at an angle of about 45 degrees to said tube
axis,
and toward an external portion of said one side of the tube, when said red
light source is energized;
a green light source located to said one side of the tube and
positioned to direct a beam of green light at an angle of about 45 degrees to
said tube axis, and toward said external portion of said one side of the tube
when said red light source is energized;
a photodetector that is responsive to red light reflection and to
green light reflection, said photodetector being located to said one side of
the
tube and positioned to view said external portion of said one side of the tube
2 0 along a view axis that extends generally normal to said tube axis;
energizing means for alternately pulse energizing said red light
source during a first time interval and said green light source during a
second
time interval;
ratio determining means responsive to a red light reflection
output from said photodetector during said first time interval, and to a green
light reflection output from said photodetector during said second time
interval; and
red blood spillover output means controlled by said ratio
determining means as a function of a ratio of said red light reflection output
to
said green light reflection output.
6b

CA 02241246 2004-07-12
According to the present invention, there is also
provided a method of monitoring a non-red blood cell tube
and detecting the quantity of red blood cells flowing in
the tube, comprising the steps of:
directing red light toward and from a side of the
tube;
directing green light toward and from a side of the
tube;
detecting a red light reflection intensity from said
side of the tube, and from red blood cells that may be
within the tube;
detecting a green light reflection intensity from said
side of said tube, and from red blood cells that may be
within the tube;
providing an output by detecting a ratio of said red
light reflection intensity to said green light reflection
intensity; and
using the output to detect the quantity of red blood
cells that is flowing in the tube.
According to the present invention, there is also
provided a method sensing red blood cell spillover into an
non-red blood cell tube, comprising the steps of:
providing a light transparent empty tube; .
providing a photosensor. to view an extema~ portion of one side
of said tube; . , .
determining a first output of said photosensor when said
photosensor views said external portion of said empty tube;
providing a red light source that is located to illuminate said
external portion of said one side of said tube with red light when said red
light
source is energized;
providing a green light source that is located to illuminate said
external portion of said one side of said tube with green light when said
green
light source is energized;
6c


CA 02241246 2004-07-12
determining a second output of said photosensor while said
photosensor views said external portion of said empty tube, and while only
said red light source is energized;
determining a third output of said photosensor while said
photosensor views said external portion of said empty tube, and while only
said green light source is energized;
establishing a compensated red photosensor output by
subtracting said first output from said second output;
establishing a compensated green photosensor output by
subtracting said first output from said third output;
providing ratio determining means;
initializing said ratio determining means by
utilizing said ratio determining means to set a ratio of
said compensated red photosensor output to said compensated
green photosensor output equal to ones
filling said tube with a non-red blood cell sample that is normally
devoid of red blood cells;
energizing only said green tight source, to thereby direct green
light toward said external portion of said frlled tube;
~ determining a fourth output of said photosensor as said
photosensor views green light that is reflected from said non-red blood
sample within said filled tube while only said green Light source is
energized;
energizing only said red light source, to thereby direct red light
toward said external portion of said filled tube;
determining a fifth output of said photosensor as said
photosensor views red light that is reflected from said non-red blood sample
within said filled tube while only said red light source is energized; and
utilizing said initialized ratio determining means to provide' a red
blood cell ~spillover output as a function of a ratio of said fifth output and
said
fourth output.
6d


CA 02241246 1998-06-29
WO 9$/20345 PCTlUS97/20086
These and other objects, advantages and features of the present
invention will be apparent to those of skill in the art upon reference to the
following detailed description of presently preferred embodiments of the
invention, the drawings and the appended claims.
BRIEF DESCRIPTION OF THE DRAWING
F(G. 1 is a schematic representation of a continuous blood separator
having three relatively transparent blood component collect tubes and a red
blood cell detector in accordance with the present invention associated with
one of the collect tubes.
FIG. 2 is a flowchart illustrating the method of the present invention.
FIG. 3 shows an embodiment of the invention wherein a platelet collect
tube has associated therewith a first emit/detect station that operates to
emit
a first color of light (red) into the collect tube, and then to detect the
reflection
of this first color from the blood component flow within collect tube, and a
second emit/detect station that operates to emit a second color of light
(green) into the collect tube, and then to detect the reflection of this
second
color from the blood component flow within the collect tube.
FIG. 4 shows an embodiment of the invention wherein a platelet collect
tube has associated therewith a first emit/detect station that operates to
emit
a first color of fight (red) into the collect tube, and to then detect the
reflection
of this first color from the blood component flow within the collect tube,
wherein a second emit/detect station is located diametrically across from the
first emit/detect station and is operative to emit a second color of light
(green)
into the collect tube, and then to detect the reflection of this second color
from
the blood component flow within the collect tube.
FIG. 5 shows a preferred embodiment of the invention wherein blood
component flow takes place perpendicular to the plane of the figure, wherein
red light and green light are projected at an angle of about 45 degrees to the
7
SUBSTITUTE SHEET (RULE 26)


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WO 98/20345 PCT/(TS97/20086
collect tube-axis of a collect tube, and wherein a single photodetector views
the collect tube along an angle generally 90 degrees to the collect tube-axis.
FIG. 6 is a flowchart showing of an initializing procedure for the
apparatus of FIG. 5.
F1G. 7 is a graph which contains a multiplicity of curves each of which
represent changes in light reflection measured at wavelengths of from 400 to
700 nm incident upon a blood sample from a donor having a relatively high
concentration of platelets, wherein the hematocrit of the samples range from
a zero hematocrit (Series 1 ) to 3% hematocrit (Series 5).
FlG. 8 is a graph which contains a multiplicity of curves similar to that
of FIG. 7, in which the blood sample is from a donor having a normal
concentration of platelets.
FIG. 9 is a graph which contains a multiplicity of curves similar to that
of FIGS. 7 and 8, in which the blood sample is from a donor having a
relatively low concentration of platelets.
Detailed Description Of The Invention
As shown in FIG. 1, conventional continuous blood separator 20
includes three relatively transparent blood component collect tubes 21, 22
and 23. Collect tube 21 is intended to carry red blood cells. Platelet collect
tube 22 is intended to carry platelets, with the flow rate of the blood
component within collect tube 22 typically in the range of from about 0.8 to
about 25 ml/min. Plasma collect tube 23 is intended to carry blood plasma.
In FIG. 1 the direction of blood component flow is from left to right, as is
shown by the arrows associated with collect tubes 21, 22 and 23, with it being
assumed that the blood being separated by separator 10 is human blood, but '
this selection is by way of example only. In this embodiment, collect tubes
21, 22 and 23 are constructed of optically transparent polyvinylchloride and
8
SUBSTITUTE SHEET (RULE 26)


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WO 98/20345 PCT/U897/z0086
are generally circular in cross section, and having an inner diameter of about
2.87 mm and an outer diameter of about 4.75 mm.
A red blood cell spillover detector 24 of the present invention is
associated with collect tube 22. While the physical spacing or distance that
exists between detector 24 and separator 20 is not critical, a utility of the
present invention includes halting separator 20 when red blood cells are
detected in platelet collect tube 22. Therefore, it may be desirable to keep
the physical separation between detector 24 and separator 20 at a minimum.
In any case, the detector 24 includes light sources and mating light
detector(s). In accordance with an important feature of the invention, both
light sources and the mating light detectors) that are within detector 24 are
located on the same side of collect tube 22.
FIG. 2 is a flowchart illustrating the present invention. As shown at
functions 10 and 11, red light and green light are directed toward the blood
collect tube that is to be monitored for the presence or spillover of red
blood
cells. As used herein, the term green light is intended to mean visible
electromagnetic radiation having a wavelength of from about 4,912 to about
5,750 angstroms, and the term red light is intended to mean visible
electromagnetic radiation having a wavelength of from about 6,470 to about
7,000 angstroms.
Funetions/method steps 10, 11 can occur during the same time
interval, in which case two light sensors or light detectors are provided, one
sensor being selectively responsive only to red light reflection and the other
sensor being selectively responsive only to green light reflection. However,
in
a preferred embodiment, the two steps 10, 11 occur during two different but
closely spaced time intervals. In this embodiment, only one sensor may be
provided, this one sensor having a wide wavelength response so that it is
responsive to red light reflection during one time interval, and is responsive
to
green fight reflection during another time interval. fn any case, the
detection
9
SUBSTITUTE SHEET (RULE 26)


CA 02241246 2003-09-12
of red light reflection and green light reflection are shown at functions 12
and
13, respectively.
At function 14 the magnitude of the red light reflection and the
magnitude of the green light reflection are compared. In a preferred
embodiment, the ratio of red light reflection magnitude to green light
reflection
magnitude is determined. While function 14 may be constructed and
arranged to directly provide an output, FIG. 2 shows a compare function 15
that compares the ratio that was determined by function 14 to a user supplied
threshold value 16, which is the minimum spillover tolerated or lacking in
adverse consequences for a given application. A function 17 then responds
to comparison 15, and provides an output when the ratio output of 14
exceeds the threshold output of 16.
FIG. 3 shows an embodiment of the invention wherein platelet collect
tube 22 has associated therewith a first emit/detect station 30 in accordance
with the invention that operates to emit a first color of light (red) into
collect
tube 22, and then to detect the reflection of this first color from the blood
component flow 32 within collect tube 22. Spaced a short distance from
station 30 is a second emitldetect station 31 in accordance with the invention
that operates to emit a second color of light (green) into collect tube 22,
and
then to detect the reflection of this second color from the blood component
flow 32 within collect tube 22. Note that in accordance with an important
feature of the invention, both the light source and its mating light detector
are
located on the same side of collect tube 22.
The two respective output conductors 34 and 35 of stations 30 and 31
25 carry electrical signals whose magnitudes are directly proportional to the
magnitude of the reflected first light and to the magnitude of the reflected
second light. An electrical signal comparator 33 in accordance with the
invention operates to compare the two signals on conductors 34, 35, and to
provide an output 36 as a result of this comparison.


CA 02241246 1998-06-29
WO 98/20345 PC7YUS97/20086
The two stations 30, 31 may operate during the same time interval
having a duration of, for example, fractions of a second. In this case the two
signals on conductors 34 and 35 also appear during this common time
interval. Signal comparator 33 may or may not include a latch means (not
shown) that operates to latch the magnitudes of these two signals 34, 35 to
enable a magnitude comparison to be made.
In accordance with an important feature of this invention, the above
described signal comparison is a comparison, such as a ratio calculation, thaf
takes advantage of the fact that red light reflection increases and green
light
reflection decreases as the concentration of red blood cells increases.
The two stations 30, 31 may also operate during two different time
intervals that are spaced from one another. In this case, the two signals on
conductors 34 and 35 also appear during these two different time intervals,
and signal comparator includes a latch means (not shown) that operates to
latch the magnitudes of these two signals 34, 35 in order to enable a
magnitude comparison to be made after expiration of the later or second of
the two time intervals.
While the physical spacing of the two stations 30, 31 along the length
of collect tube 22 is not critical to the invention, it may be desirable to
maintain this spacing to a minimum, and/or to time the later operation of
station 31, relative to the earlier operation of station 30, as a function of
the
flow rate of the blood component 32 that is within collect tube 22. In this
way,
both station 30 and station 31 operate on the same flowing volume of blood
component 32.
FIG. 4 shows an embodiment of the invention wherein platelet collect
tube 22 has associated therewith a first emit/detect station 40 in accordance
with the invention that operates to emit a first color of light (red) info
collect
tube 22, and to then detect the reflection of this first color from the blood
component flow 32 within collect tube 22. Located diametrically across from
station 40 is a second emit/detect station 41 in accordance with the invention
11
SUBSTITUTE SHEET (RULE 26)


CA 02241246 2003-09-12
that operates to emit a second color of light (green) into collect tube 22,
and
then to detect the reflection of this second color from the blood component
flow 32 within collect tube 22.
Two respective output conductors 44 and 45 of stations 40 and 41
carry electrical signals whose magnitudes are directly proportional to the
magnitude of the reflected first light and to the magnitude of the reflected
second light. An electrical signal comparator 33 in accordance with the
invention operates to compare the two signals on conductors 44, 45, and to
provide an output 36 as a result of this comparison.
The two stations 40, 41 may operate during the same time interval,
whereupon the two stations 40, 41 include individual light detectors that are
selectively responsive only to the first light for the detector of station 40,
and
to the second light for the detector of station 41. 1n this case, the two
signals
on conductors 44 and 45 also appear during this time common interval.
Comparator 33 rnay or may not include a latch means (now shown) to latch
the magnitudes of these two signals 44, 45 as the signal comparison is made.
The two stations 40, 41 may also operate during two different time intervals.
In this case, the light detector that is within each of the two stations 40,
41 is
rendered operative only during the period of operation of that respective
station 40, 41. Since interference is precluded by providing different time
periods of operation for the two light detectors, the two light detectors may
be
of a relatively wide color response. The two electrical signals on conductors
44 and 45 also appear during these two different time intervals, and signal
comparator 33 in this case includes a latch means (not shown) that operates
to latch the magnitudes of these two signals 44, 45 in order to enable a
comparison to be made after expiration of the later or second time interval.
Note that in accordance with an important feature of the invention, each
individual light source and its mating light detector are located on the same
side of collect tube 22.
12


CA 02241246 1998-06-29
WO 98/20345 PCT/US97/20086
- !n accordance with an important feature of this invention, the signal
comparison provided at 33 is a comparison, such as a ratio calculation, that
' takes advantage of the fact that red light reflection increases and green
light
reflection decreases as the concentration of red blood cells increases.
FIG. 5 shows a preferred embodiment of the invention wherein blood
component flow takes place through a three dimensional volume 50 that is
defined by the intersection of a red-light beam 52 and a green-light beam 51.
The direction of blood component flow relative to the plane of FIG. 5 is not
critical. For example, flow may be perpendicular to the plane of FIG. 5, flow
may be in the plane of FIG. 5, or flow may take place at an angle to the plane
of FIG. 5. That is, area 50 represents a generally spherical volume that
carries the blood component flow to be monitored, for example this flow may
take place within a circular cross section, visually transparent, collect tube
as
previously described.
The two linear, rod-shaped beams 51 and 52 of FIG. 5 generally
designate a beam of green light that is emitted from a green LED 53, and a
beam of red light 52 that is emitted from a red LED 54. Beams 51, 52 are, far
example, circular in cross section. In this embodiment of the invention, light
beams 51, 52 are directed at an angle of about 45 degrees to a horizontal
reference axis 55 that extends in the plane of F1G. 5, i.e. beams 51, 52
define
an included angle 58 of about 90 degrees.
A photosensor 56 that is responsive to both green Light reflection and
red light reflection is positioned to view volume 50 and the red light and
green
light that is reflected therefrom. This reflection takes place along a
photosensor view axis 59 that extends downward at about 90 degrees to
reference axis 55, i.e. photosensor view axis 59 generally bisects angle 58.
While not critical to the invention, sensor 56 comprises a photodiode, having
a size of about 2.92 mrn.
LEDs 53, 54 and photosensor 56 are all located in a common plane
that includes volume 50, i.e., for example, they may be located in the plane
of
13
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WO 98/20345 PCT/US97/20086
FIG. 5, or they may be located in a common plane that is inclined to the plane
of FIG. 5. In any case, as will be appreciated, the detailed construction and
arrangement of FIG. 5 provides a number of mechanical or physical support '
surfaces and the like. In operation, photosensor 56 operates to detect red
light and green light that is reflected off of these various surfaces as well
as
from the blood components that are flowing through volume 50.
In accordance with a feature of the invention, LEDs 53, 54 are pulsed
off and then on at the rate of about 2 Khz, with a generally equal off/on duty
cycle. This pulse energization of LEDs 53, 54 is time-staggered such that
one LED is on during the time interval that the other LED is off.
The two output signals that are provided by photosensor 56, i.e. a red
light reflection output during one time interval, and a green light reflection
output during a second time interval, are now processed by a signal
comparator such as 33 of FIGS. 3 and 4, in accordance with FIG. 2. With this
FIG. 5 construction and arrangement, the hematocrit is about 1 percent when
this ratio equals about 1.5. Using the unique ratio calculation of this
invention
accommodates changes in surface finish of the apparatus, changes in
cleanliness, changes in alignment and physical orientation of the apparatus
parts, optoelectronic component changes, etc., all of which may occur
between testing runs and with the passage of time.
In order to initialize the apparatus of FIG. 5 the procedure shown in
FIG. 6 is followed. At function 60, a dry, empty cassette is positioned in a
red
blood cell spillover detector 24 in which LEDs 53 and 54 are off. The blood
separation system 20 of which the detector 24 is a part immediately and
automatically detects the presence of an empty cassette (function 61 ) and is
programmed to immediately proceed to perform a series of operations to
adjust a compensated red/cornpensated green ratio to 1 prior to introduction
of blood into the cassette.
Initially, the red LED 53 is_energized for eight cycles with an LED which
functions at 2000 cycfeslsecond, as shown at function 62. During each of the
14
- SUBSTITUTE SHEET (RULE 26)


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WO 98/20345 - PC'd'/US97/20086
eight cycles energizing red LED 53, two sample measurements are taken and
stored, and represent reflected red light on values, as shown at function 63.
Thereafter, red LED 53 is deenergized (function 64), during which time two
sample measurements are taken and designated reflected red light off values,
as shown at function 65. The functions 62, 63, 64 and 65 are repeated seven
more times, that is, until sixteen reflected red light on measurements are
collected and sixteen reflected red light off measurements are collected.
Thereafter, the average reflected red fight is determined by averaging the
sixteen reflected red light on measurements, averaging the sixteen eight
reflected red light off measurements, and subtracting the average reflected
red light off from the average reflected red light on, as shown at function
66.
The green LED 54 is then energized for eight cycles with an LED
which also functions at 2000 cycles/second, as shown at function 67. During
each of the eight cycles energizing green LED 54, twa sample measurements
are taken and stored, and represent reflected green light on values, as shown
at function 68. Thereafter, green LED 54 is deenergized (function 69), during
which time two sample measurements are taken and designated reflected
green light off values, as shown at function 70. The functions 67, 68, 69 and
70 are repeated seven more times, that is, until sixteen reflected green light
on measurements are collected and sixteen reflected green tight off
measurements are collected. Thereafter, the average reflected green light is
determined by averaging the sixteen reflected green fight on measurements,
averaging the sixteen reflected green light off measurements, and subtracting
the average reflected green light off from the average reflected green light
on
(function 71 ).
The FIG. 6 initializing procedure is completed at function 72 by setting
the calculated red/green ratio to be equal to the value "one", which may be
accomplished by adjusting the energizing current to the green LEDs 54. If a
value of "one" cannot be achieved with such an adjustment, the system is
placed in an alarm condition. Note that it is not critical to the invention
SUBSTITUTE SHEET (RULE 26)


CA 02241246 1998-06-29
WO 98120345 PCT/US97/20086
whether the average reflected red light is determined (steps 62-66) before or
after the average reflected green fight is determined (steps 67-71 ). In
addition, it should be understood that before step 72 is performed and the '
compensated red/compensated green ratio is set to one, as described above,
multiple repetitions of steps 62-71 may be performed, thereby providing
additional data for the average reflected light values and the redJgreen
ratio.
Furthermore, it should also be understood that while in the presently
preferred
embodiment, a specific number of measurements and cycle frequencies are
disclosed, the number, frequency, and pattern of measurements and cycles
may be varied.
Blood then is introduced into the cassette, and as it flows therethrough,
reflected red light and reflected green light are repeatedly measured as
described in steps 62-71. After each pair of average reflected red light and
reflected green light values are obtained (steps 66 and 71 ), a ratio of
reflected
red to reflected green is obtained. If the ratio of reflected red to reflected
green reaches or exceeds predetermined limits, than a spillover condition is
indicated.
Referring now to F1G. 7, changes in reflection of light of wavelengths of
from 400 to 700 nm incident upon a blood sample from a donor having a
relatively high concentration of platelets are plotted. The blood sample
tested
in Series 1 had a zero hematocrit (hct), the sample tested in Series 2 had a
0.1% hct, the sample tested in Series 3 had a 0.5% hct, the sample tested in
Series 4 had a 1 % hct and the sample tested in series 5 had a 3% hct. The
approximate ratios of reflected red light of approximately 700 nm to reflected
green light of approximately 550 nm from FIG. 7 are summarized in Table I.
16
SUBSTITUTE SHEET (RULE 26)

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WO 98/20345 d'CT/iT897/Z0086
TABLE I
SERIES HEMATOCRIT REFLECTED RED RATIO


REFLECTED GREEN


1 0% 9-33 0.9


10


~ 2 0.1 % 9-33 1.1


8.6


3 0.5% 9-22 1.5


6.2


4 1 % 9_3 - 1.7


5.4


3 % ,~ 0 - 2.0


4.9


As can been seen clearly in Table I, there is a trend of increase in the ratio
of
reflected red to reflected green light from a zero hematocrit to a hematocrit
of
5 3%, and even a differentiation between a zero hematocrit sample and a
sample having a hemotocrit of 0.1
Referring now to FlG. 8, changes in reflection of light of wavelengths of
from 400 to 700 nm incident upon a blood sample from a donor having a
relatively normal concentration of platelets are plotted for samples in which
hematocrit is varied in a similar manner to the Series illustrated in FIG. 7.
The
approximate ratios of reflected red light of approximately 700 nm to reflected
green light of approximately 550 nm from FIG. 8 are summarized in Table Il.
TABLE II
SERIES HEMATOCRIT REFLECTED RED RATIO


REFLECTED GREEN


1 0% 7-88 _. 1.0


8.1


2 0.1 % 8'0 1.2


6.9


3 0.5% 7-99 1.5


5.3


_ 4 1 % 8-00 1.7


4.7


5 3% 9-00 2.1


4.3


17
SUBSTITUTE SHEET (RULE 26)


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As can been seen clearly in Table II, there is a trend of increase in the
ratio of
reflected red to reflected green light from a zero hematocrit to a hematocrit
of
3% which is substantially the same as measured for the blood sample ,
having a high concentration of platelets. Once again, there is a
differentiation
between a zero hematocrit sample and a sample having a hematocrit of 0.1
Referring now to FIG. 9, changes in reflection of light of wavelengths of
from 400 to 700 nm incident upon a blood sample from a donor having a
relatively low concentration of platelets are plotted for samples in which
hematocrit is varied in a similar manner to the Series illustrated in FIGS. 7
and 8. The approximate ratios of reflected red light of approximately 700 nm
to reflected green light of approximately 550 nm from FIG. 9 are summarized
in Table III.
TABLE III
SERIES HEMATOCRIT REFLECTED RED RATIO


REFLECTED GREEN


1 0% _7.7 1.0


7.7


2 0.1 % _7.7 1.1


7.0


3 0.5% _7.7 1.4


5.3


4 1 % _7.7 1.7


4.6


5 3% _8.8 2.0


4.3


As can been seen clearly in Table III, there is a trend of increase in the
ratio
of reflected red to reflected green light from a zero hematocrit to a
hematocrit
of 3% which is substantially the same as measured for the blood samples
having high and normal concentrations of platelets. Once again, there is a ,
differentiation between a zero hematocrit sample and a sample having to a
hematocrit of 0.1
A review of the data shown in FIG. 6 and summarized in Table I in
combination with the data shown in FIG. 7 and summarized in Table II
18
SUBSTITUTE SHEET (RULE 26)

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WO 98/20345 PCT/US97/20086
indicates that blood samples having higher platelet concentrations may be
differentiated from blood samples having lower platelet concentrations using
' the technique of the present invention. For example, green light reflection
of
blood samples having a zero hematocrit (Series 1) decreases from a high
platelet concentration value of approximately 10 to a normal platelet
concentration value of approximately 8. Also by way of example, green light
reflection of blood samples having a 1 % hematocrit (Series 4) decreases from
a high platelet concentration value of approximately 5.6 to a normal platelet
concentration value of approximately 4.5. Thus, platelets have been found to
affect reflection of light as a function of concentration and/or density.
In yet another embodiment, polyvinyl cassettes used to evaluate blood
samples using the technique of the present invention were treated with hot
stamp foil rectangle approximately'/z" by 1" of one of three colors--black,
gray
{foil No. LT12106) and white {No. CC11206). Reflectivity of green and red
light as described above was measured on blood samples having differing
hematocrit values. The results are summarized below in Table IV.
TABLE IV
HEMATOCRIT REFLECTED RATIO
RED


REFLECTED REEN
G


w/blackwlgray w/whitew/blackw/gray w/white


back- back- back- back- back- back-


ground ground ground ground ground ground


no _5


cassette 20


empty 185 636 944


cassette 136 292 886


0% _52 _775 1018 2.2 2.2 1.1


24 349 942


0.5% _60 752 985 3.3 4.0 1.5


18 187 646 --


1 % _69 725 936 4.6 4.6 2.0


15 156 480


2% _90 705 888 6.4 5.9 2.3


14 119 390


3% 128 687 844 6.4 6.5 2.5


20 105 339


19
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WO 98/20345 PCT/US97/20086
A review of the data shown in Table IV indicates how the empty
cassettes marked with selected black, gray and white foil have distinguishing
'
reflectivity. This varying reflectivity may be used, for example, to indicate
the
nature of the disposable set mounted to the blood separator, or may be
indicative of the blood components to be collected, or both. The data shown
in Table IV also appears to indicate that regardless of the presence of the
foils identified above and attached to the cassettes tested, there remains a
trend of increasing ratio of red reflectivity to green reflectivity in blood
samples, as hematocrit increases in the blood samples.
The present invention has been described in detail while making
reference to various embodiments thereof, including the preferred
embodiment thereof. Since it is apparent that those skilled in the art to
which
this invention relates, will, upon learning of the invention, visualize yet
other
embodiments that are within the spirit and scope of the invention, the
forgoing
detailed description is not to be taken as a limitation on the spirit and
scope of
this invention.
SUBSTITUTE SHEET (RULE 26)

Representative Drawing
A single figure which represents the drawing illustrating the invention.
Administrative Status

For a clearer understanding of the status of the application/patent presented on this page, the site Disclaimer , as well as the definitions for Patent , Administrative Status , Maintenance Fee  and Payment History  should be consulted.

Administrative Status

Title Date
Forecasted Issue Date 2006-04-11
(86) PCT Filing Date 1997-11-04
(87) PCT Publication Date 1998-05-14
(85) National Entry 1998-06-29
Examination Requested 2001-07-03
(45) Issued 2006-04-11
Deemed Expired 2010-11-04

Abandonment History

There is no abandonment history.

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Application Fee $300.00 1998-06-29
Registration of a document - section 124 $100.00 1998-10-30
Maintenance Fee - Application - New Act 2 1999-11-04 $100.00 1999-09-20
Maintenance Fee - Application - New Act 3 2000-11-06 $100.00 2000-02-22
Registration of a document - section 124 $50.00 2000-07-17
Request for Examination $400.00 2001-07-03
Maintenance Fee - Application - New Act 4 2001-11-05 $100.00 2001-10-01
Maintenance Fee - Application - New Act 5 2002-11-04 $150.00 2002-09-25
Maintenance Fee - Application - New Act 6 2003-11-04 $150.00 2003-09-29
Maintenance Fee - Application - New Act 7 2004-11-04 $200.00 2004-09-24
Maintenance Fee - Application - New Act 8 2005-11-04 $200.00 2005-09-29
Final Fee $300.00 2006-01-25
Maintenance Fee - Patent - New Act 9 2006-11-06 $200.00 2006-10-05
Registration of a document - section 124 $100.00 2007-03-14
Maintenance Fee - Patent - New Act 10 2007-11-05 $250.00 2007-10-09
Maintenance Fee - Patent - New Act 11 2008-11-04 $250.00 2008-10-09
Registration of a document - section 124 $100.00 2008-10-31
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
CARIDIANBCT, INC.
Past Owners on Record
COBE LABORATORIES, INC.
GAMBRO BCT, INC.
GAMBRO, INC.
GIBBS, BRUCE W.
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Representative Drawing 1998-09-25 1 6
Drawings 2003-09-12 8 153
Description 2003-09-12 24 1,110
Claims 2003-09-12 7 245
Description 2004-09-20 25 1,119
Claims 2004-09-20 7 263
Description 2001-11-16 24 1,108
Abstract 1998-06-29 1 56
Description 1998-06-29 20 961
Claims 1998-06-29 7 240
Drawings 1998-06-29 8 153
Cover Page 1998-09-25 2 73
Description 2004-07-12 24 1,109
Claims 2004-07-12 7 247
Representative Drawing 2006-03-14 1 9
Cover Page 2006-03-14 1 49
Assignment 1998-10-30 2 56
Correspondence 1998-09-02 1 29
PCT 1998-06-29 4 138
Assignment 1998-06-29 5 124
Assignment 2000-07-17 5 102
Correspondence 2000-07-17 4 68
Prosecution-Amendment 2001-07-03 1 30
Prosecution-Amendment 2001-10-11 2 43
Prosecution-Amendment 2001-11-16 8 293
Prosecution-Amendment 2003-03-31 3 92
Prosecution-Amendment 2003-09-12 17 607
Assignment 2008-10-31 4 132
Prosecution-Amendment 2004-09-20 9 279
Correspondence 2007-03-16 3 65
Assignment 2007-03-14 7 238
Prosecution-Amendment 2004-01-21 2 49
Prosecution-Amendment 2004-07-12 6 218
Correspondence 2006-01-25 1 30
Correspondence 2010-08-10 1 46