U.S. patent number 3,892,236 [Application Number 05/346,729] was granted by the patent office on 1975-07-01 for apparatus for filtration-leukopheresis for separation and concentration of human granulocytes.
Invention is credited to Isaac Djerassi.
United States Patent |
3,892,236 |
Djerassi |
* July 1, 1975 |
Apparatus for filtration-leukopheresis for separation and
concentration of human granulocytes
Abstract
Apparatus of simple character is provided for continuous
withdrawal of blood from a human donor, forced extracorporeal
circulation of blood of the donor with separation of granulocytes,
and return by gravity of the leukocyte-poor whole blood to the
donor.
Inventors: |
Djerassi; Isaac (Philadelphia,
PA) |
[*] Notice: |
The portion of the term of this patent
subsequent to April 9, 1991 has been disclaimed. |
Family
ID: |
23360790 |
Appl.
No.: |
05/346,729 |
Filed: |
April 2, 1973 |
Current U.S.
Class: |
604/6.03 |
Current CPC
Class: |
A61M
1/3621 (20130101); A61M 1/3496 (20130101); A61M
2202/0441 (20130101); A61M 1/0011 (20130101); A61M
2202/0413 (20130101); A61M 2202/0413 (20130101); A61M
2230/005 (20130101); A61M 2202/0441 (20130101); A61M
2202/0057 (20130101) |
Current International
Class: |
A61M
1/34 (20060101); A61M 1/36 (20060101); A61M
1/00 (20060101); A61m 001/03 () |
Field of
Search: |
;128/213,214R,214F,214B,214C,214.2,276,278 ;23/258.5 ;210/23 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Primary Examiner: Truluck; Dalton L.
Attorney, Agent or Firm: Wobensmith, 2nd; Zachary T.
Wobensmith, III; Zachary T.
Claims
I claim:
1. Apparatus for filtration-leukopheresis comprising
a venous blood supply connection adapted to be connected to a
donor,
a venous blood return connection adapted to be connected to the
donor,
a leukocyte separating and retaining filter interposed in series
with said connections and in fluid communication therewith for
extracting leukocytes from blood passing therethrough,
a permanently vented receptacle in continuous communication with
the atmosphere interposed in series between said filter and said
return connection and in fluid communication therewith,
fixedly mounted detachable supporting members for said filter and
said vented receptacle, and
power driven pump means upstream of said receptacle for
continuously delivering blood from said supply connection to and
through said filter and to said vented receptacle.
2. The combination defined in claim 1 in which
said last mentioned means includes members for impelling said blood
under constant positive air pressure.
3. The combination defined in claim 1 in which
said last mentioned means includes a plurality of flexible
receptacles for alternate receipt and delivery of blood from the
donor, and
pressure and vacuum applying means for activating said flexible
receptacles.
4. The combination defined in claim 1 in which
said last mentioned means includes a constant volume continuous
impelling menber.
5. The combination defined in claim 4 in which
said impelling member is a constant volume pump.
6. The combination defined in claim 5 in which
said pump has a counter actuated thereby.
7. The combination defined in claim 1 in which
said filter and said receptacle are interconnected and have supply
and delivery connections to provide a replaceable unit for
individual use by a donor.
8. A replaceable unit as defined in claim 7 in which
said supply pipe has a plurality of flexible blood receiving
receptacles interposed therein.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to apparatus for filtration-leukopheresis
for separation and concentration of large amounts of normal human
granulocytes.
2. Description of the Prior Art
It has heretofore been proposed to extract blood from a human donor
for use as whole blood, for separation of plasma, for separation of
granulocytes or other blood components primarily for the purpose of
transfusion to individuals in need of such components.
Blood removal and collection apparatus has taken various forms and
reference may be had to the U.S. Pat. Nos. to Strumia, 2,845,929,
Gewecke et al., 2,757,669, Welch, Jr., 2,982,286, Rieutord et al.,
2,757,375, Poitras, 2,784,932 Erikson, 2,597,715, and Judson et
al., 3,489,145.
The delivery of blood plasma and the like to a patient for
transfusion can be effected by gravity or by applied pressure as
shown in the U.S. Pat. No. to Rundhaug, 2,842,123.
The harvesting of normal granulocytes with special continuous flow
centrifugation (Freirach, E. J., et al., Separation and collection
of leukocytes. Cancer Res. 25: 1516-1520 (1965) is inefficient and
impractical for widespread use.
The batch treating of whole blood to remove leukocytes with a
filter is shown in the U.S. Pat. No. to Greenwalt, 3,462,361.
It has heretofore been undertaken to withdraw blood from a donor,
in a plastic bag with saline solution and a mixture of heparin,
saline and sodium citrate selectively delivered to the plastic bag
and then transferring the fluid through two leukocyte filters and
then advance the blood by manual manipulation to another plastic
bag for return through a tube to the donor, a second source of
saline solution being connected to the return tube. The respective
tubes were controlled by hemostats for manual regulation and the
entire procedure was manual.
Very close supervision and control by trained personnel has been
required and the time for the filtration-leukopheresis has required
about some 4 hours or more with each individual donor.
In my prior application for U.S. Letters Pat. filed May 18, 1972,
Ser. No. 254,609, now U.S. Pat. No. 3,802,432 issued Apr. 9, 1974,
there is described apparatus for separation and retention of human
granulocytes with which the weight of the blood in intermediate
receptacles in its circuit from and to the body of the donor is
utilized to control the flow.
In my prior application for U.S. Letters Pat. filed Dec. 20, 1972,
Ser. No. 317,057, improved apparatus is shown.
The present invention comprises simplified apparatus utilizing in
one embodiment constant volume of blood from the donor and to and
through the granulocyte separating filter and in another embodiment
constant pressure of the blood from the donor to and through the
filter in both instances for effecting the flow through the
apparatus to a receptacle for gravity return of leukocyte-poor
whole blood to the donor.
SUMMARY OF THE INVENTION
In accordance with the present invention apparatus is provided for
harvesting granulocytes from a single donor and within a relatively
short period of time and which includes a filter connected to a
vented blood return receptacle, the blood being delivered to and
through the filter to the return receptacle either by constant
volume or by constant pressure delivery to the filter.
It is the principal object of the invention to provide apparatus
for harvesting granulocytes from human blood of a donor with return
of the leukocyte-poor blood to the donor which is of simplified
construction, which requires a minimum of attention and which will
permit of rapid cycling and attendant short period of retention of
the donor.
It is a further object of the invention to provide apparatus of the
character aforesaid in which the filter and the blood return
receptacle and associated tubing may be supplied as a disposable
unit for connection to a permanently installed withdrawal and
delivery apparatus.
It is a further object of the invention to provide apparatus of the
character aforesaid in which the withdrawal and delivery apparatus
may selectively be such as to effect a constant volume or a
constant pressure transfer of the blood from the donor.
Other objects and advantageous features of the invention will be
apparent from the description and claims.
BRIEF DESCRIPTION OF THE DRAWINGS
The nature and characteristic features of the invention will be
more readily understood from the following description taken in
connection with the accompanying drawings forming part hereof, in
which:
FIG. 1 is a diagrammatic view of a preferred form of apparatus in
accordance with the invention utilizing constant pressure for blood
delivery; and
FIG. 2 is a diagrammatic view of another preferred form of
apparatus in accordance with the invention, utlizing constant
volume for blood delivery.
It should, of course, be understood that the description and
drawings herein are illustrative merely and that various
modifications and changes can be made in the structure disclosed
without departing from the spirit of the invention.
Like numerals refer to like parts throughout the several views.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now more particularly to FIG. 1 of the drawings, a fluid
connection 10 of flexible tubing, has a needle (not shown) of well
known type, and preferably of 15 gauge, on its free end for
insertion into a vein in one arm A1 of the donor for withdrawing
blood.
The fluid connection 19 preferably extends to branch connections 11
and 12 of flexible tubing and past inlet control valves 13 and 14,
which may be non-return valves or positively positioned valves. The
valves 13 and 14 preferably act externally of and are adapted to
pinch or release the tubes 11 and 12. The pipes 11 and 12 extend to
flexible blood receiving receptacles 15 and 16, preferably of inert
transparent or translucent synthetic plastic, suspended from fixed
brackets 17 and 18 in rigid enclosing cylinders 19 and 20. The
cylinders 19 and 20 are preferably transparent for observation of
the receptacles 15 and 16 and each has its interior alternately
placed under vacuum and under pressure and phased so that when
cylinder 19 is under vacuum cylinder 20 is under pressure.
Vacuum pipes 23 and 24, connected to a suitable source of vacuum VP
and connected to the cylinders 19 and 20 through control valves 25
and 26 and pressure supply pipes 27 and 28, connected to a suitable
source of pressure PP through control valves 29 and 30, permit
alternate pressure and vacuum application in cylinders 19 and
20.
The receptacles 15 and 16 are connected by fluid delivery
connections 33 and 34, of flexible tubing, past control valves 35
and 36, which may be non-return valves or positively positioned
valves. The valves 35 and 36 preferably act externally of and are
adapted to pinch or release the tubes 33 and 34. The pipes 33 and
34 extend to a pipe 37 which is connected to a filter 38 which
delivers blood either directly to pipe 44 or through pipe 39 to and
through a transparent chamber 40 in which the flow of blood can be
observed directly. The filter 38 can be of any suitable type which
separates and retains granulocytes and permits the passage of
leukocyte-poor whole blood for return to the donor. Filters
identified as Leuko-Pak Leukocyte Filter available from Fenwal
Laboratories, Division of Travenol Laboratories, Inc., Morton
Grove, Illinois, and which utilize nylon fibers for adherence
thereto of the granulocytes, have been found satisfactory.
The unit comprising the pendant filter 38 and chamber 40, if used,
are preferably supported by a stand 41 having a hook 42 for
detachable engagement by a ring 43 on the bag 37.
The filter assembly 38 and 40 is connected by a pipe 44 to the
lower part of a vented blood return receptacle 45.
The receptacle 45 is preferably supported on the stand 41 by a hook
47 for detachable engagement by a ring 48 on the receptacle 45.
The receptacle 45 has an air vent tube 49 extending upwardly to
close to the top of the receptacle 45 to prevent pressure build-up
within the receptacle 45.
The receptable 45 is connected through a transparent sight tube 53
by a flexible tube 52 which has a needle (not shown) of well known
type and preferably of 15 gauge on its free end for insertion into
a vein in the other arm A2 of the donor for return, by gravity of
granulocyte-poor whole blood to the donor.
The structure, irreversibly connected, comprising the fluid
connection 10, tubes 11 and 12, receptacles 15 and 16, pipes 33 and
34, pipe 37, filter 38 with or without chamber 40, pipe 44, vented
receptacle 45 and pipe 52 with its sight tube 53 can be made as a
single use unit one for each donor pre-sterilized and in a sealed
protective package. The necessity for breaking sterile points of
connection at the time of usage will thus be avoided. Quick removal
and replacement can be effected.
Referring now to FIG. 2 of the drawings, a fluid connection 10 of
flexible tubing is provided, as before, to a needle for withdrawing
blood from a vein in one arm A1 of the donor.
The fluid connection 10 is connected to the inlet side of a
variable speed positive displacement liquid pump 60. The pump 60,
as a positive displacement pump, will have a constant volume
delivery per revolution irrespective of the speed of rotation and
can have a revolution counter 61 connected thereto and calibrated,
if desired, in accordance with the liquid volume delivery of the
pump 60.
The delivery side of the pump 60 is connected by a flexible pipe 62
to a filter 38, of the type previously described, for delivery to a
vented blood return receptacle 45.
The receptacle 45 is connected by a flexible tube 52 for return by
gravity, of granulocyte-poor whole blood to a needle in a vein in
the arm A2 of the donor.
When suction of the blood through filter 38 by the pump is
preferred, the pump is located to apply its action on pipe 44. In
this case pipe 44 may be of special material with increased
resiliency such as siliconized rubber or plastic.
The structure, irreversibly connected, comprising the pipe 62,
filter 38, with or without chamber 40, pipe 44, vented receptacle
45, and pipe 52 with or without a transparent chamber, can be made
as a single use unit similar to that previously described.
In the form of the invention shown in FIG. 1, the blood is
withdrawn from a vein in the arm A1 of the donor by the suction
alternately created in the cylinders 19 and 20 and therein on the
flexible receptacles 15 and 16 and therefrom in the fluid
connection 10. The blood in the receptacles 15 and 16 is then
alternately delivered under pressure through the pipe 37, through
the filter 38 under pressure and through the pipe 39 and chamber 40
under pressure which pressure by reason of the alternating delivery
from the receptacles 15 and 16 is substantially constant.
In the filter 38 the granulocytes are separated from the whole
blood, and collected in the filter 38 for subsequent recovery, the
leukocyte-poor whole blood still under pressure being delivered to
the vented receptacle 45.
The leukocyte-poor blood is then returned by gravity to a vein in
the arm A2 of the donor through the return pipe 52, the height of
the receptacle 45 being such as to insure adequate rate of return
of the blood and the receptacle 45 providing the desired storage
capacity for continuous return of blood.
In the form of the invention shown in FIG. 2, the blood is
withdrawn from a vein in the arm A1 of the donor by the suction of
the pump 60 and continuously delivered with constant volume through
the pipe 62 to the filter 38.
The blood is delivered to and through the filter 38 under pressure
or by suction through the filter 38 by the continuity of flow and
to the vented receptacle 45, as before.
The granulocyte-poor whole blood in the receptacle 45 is returned
by gravity to a vein of the donor as previously explained.
The quantity of blood delivered by the pump 60, can be measured by
the counter 61 which functions as a volume meter.
* * * * *