Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS3780935 A
Publication typeGrant
Publication dateDec 25, 1973
Filing dateJul 10, 1972
Priority dateJul 10, 1972
Also published asDE2340199A1, DE2340199B2
Publication numberUS 3780935 A, US 3780935A, US-A-3780935, US3780935 A, US3780935A
InventorsJacoby I, Lukacs M
Original AssigneeLukacs & Jacoby Ass
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Serum separating method
US 3780935 A
Abstract
The separation of a sample of blood into serum and clot portions is accomplished by means of a sealant consisting essentially of a silicone fluid and silica dispersed therein. The separation is accomplished by inserting a device containing a supply of the sealant into a container holding a sample of the blood, the device being characterized by a nozzle portion which extends into the sample. The container and device are centrifuged so that it separates into serum and clot portions and the sealant, having a specific gravity of at least 1.026, separates the two portions.
Images(1)
Previous page
Next page
Claims  available in
Description  (OCR text may contain errors)

United States Patent [191 Lukacs et al.

[ Dec. 25, 1973 SERUM SEPARATING METHOD Inventors: Michel J. Lukacs, Goshen, N.Y.; [an

H. Jacoby, Franklin Lakes, NJ.

Assignee: Lukacs & Jacoby Associates,

Goshen, NY.

Filed: July 10, 1972 Appl. No.: 270,278

US. Cl 233/1 A, 210/65, 210/83 Int. Cl 801d 21/26 Field of Search 106/287 SB; 210/65,

210/83, DIG. 23; 233/1, 26

References Cited UNITED STATES PATENTS 3/1972 Adler ..2l0/83 4/1970 Coleman ..2lO/83 Primary Examiner-Samih N. Zahama Assistant Examiner-Robert G. Mukai Attorney.lohn A. Mitchell et al.

ABSTRACT 3 Claims, 8 Drawing Figures PATENTED M825 I975 FIG. 4

FIG. 2 FIG. 3

SERUM SEPARATING METHOD BACKGROUND OF THE INVENTION This invention relates to a method, apparatus and composition of matter for separating a blood sample by centrifuging into clot portions, so that the serum may be quickly and readily removed without contamination by the clot portion.

In recent years, biomedical and hospital laboratories have been faced with increasing demands for more and more routine, as well as specialized, diagnostic tests of blood samples. To meet the demands of these tests equipment has been devised which automatically takes a sample or specimen of blood which has been placed in a cup and subjects it to a series of programmed tests which eventuate in a readout on a record member. While these analyzers have increased the efficiency of performing the necessary tests, a problem has continued in finding ways and means of separating the serum from the clot portion and removing the serum for analysis. Various types of tube and plug devices have been suggested by the prior art. For example, in U.S. Pat. No. 3,512,940, issued May 19, 1970, a device consisting of a tube with a filter at one end thereof is inserted into a second but larger diameter tube containing a sample of the material desired to be filtered. In U.S. Pat. No. 3,508,653, issued Apr. 28, 1970, a piston in the form of a solid plug is driven through a centrifuged blood sample so as to position itself between the serum and clot portions of the centrifuged sample. The tube within the tube concept of US. Pat. No. 3,512,940 suffers from the apparent deficiency of being costly and not readily adaptable for disposal after a single use. The plug' arrangement of US. Pat. No. 3,508,653 has the shortcoming of utilizing a solid plug member which when subjected to a substantial centrifugal force, may also develop radial forces acting against the side of the sample tube, thus creating the danger of breakage.

SUMMARY OF THE INVENTION a silicone fluid and silica. The sealant has a specific gravity of at least 1.026 and preferably in the range of 1.030 to 1.050. As such, it will normally be at the proper specific gravity to divide the serum and clot portions of the centrifuged sample, sealing the clot in the container while the serum is removed.

Accordingly, it is an object of the present invention to provide a simple and effective method of obtaining a serum sample during centrifuging.

DESCRIPTION OF THE DRAWINGS FIG. 4 is a view similar to FIG. 2 wherein the blood, the sample tube and dispenser have been subjected to the complete centrifuging step;

FIG. 5 is a sectional view of the sample tube with the separator in place overlying the clot portion with the serum portion removed;

FIG. 6 is an enlarged sectional view of the sealant dispenser showing the sealant contained therein;

FIG. 7 is a top view of the dispenser of FIG. 6; and

FIG. 8 is a bottom view of the dispenser of FIG. 6.

DESCRIPTION OF THE ILLUSTRATED EMBODIMENT Referring to the drawings, a container 10 for holding a blood sample is illustrated as a straight side wall sample tube 10 with an open top end 11. Into the open top 11 is inserted a dispenser 12. The dispenser 12 has a flange member 14 which overlies the top edge 16 of the side wall 18 of the container. The dispenser 12 includes a body portion 19; consisting of three ring sections 20, 22 and 24. Extending from the body 19 is an elongated nozzle portion 26 and at the end of the nozzle 26 is a tip 28 having an opening 30 therein. The purpose of the three rings 20, 22 and 24 is to permit the dispenser 12 to be used with containers of various diameters. Ring 20 has a shoulder 32 and a side wall 33,-ring 22 a shoulder 34 and a side wall 35, and ring 24 has a shoulder 36 and a side wall 37. When using a narrow container, the dispenser bears on the top edge of the side wall of the container at one of the shoulders 32, 34 or 36 and the side wall of the next smaller ring is parallel with the inner side wall of the container. During centrifuging the relationship between the inner surface of the container and the side wall of the ring insures stability of the dispenser during this period.

By utilizing a dispenser as illustrated herein, it is possible to use one dispenser for varying diameter containers.

The body portion 19 of the dispenser has an open end 37 over which is placed a seal 38. The seal 38 has a small opening 40 therein. The seal 38 is not placed over the open end until a sealant 42 has been placed in the dispenser.

The sealant 42 consists essentially of a silicone fluid with an inert filler, such as silica, dispersed therein. The sealant should have a specific gravity of at least 1.026

. and preferably in the range of 1.030 to 1.050.

The normal specific gravity of blood as determined by the pycnometric method is considered to be in the range of 1.048 to 1.066 with averages of 1.052 to 1.063. After centrifuging the specific gravity of the blood serum which separates from the remainder of the blood is at least 1.026 and in the range of 1.026 to 1.031. The specific gravity of the heavier portions such as the erythrocytes is 1.092 to 1.095.

In selecting a sealant it is necessary to select one which has a specific gravity greater than that of the serum portion. Accordingly, the sealant should have a specific gravity of at least 1.026. However, its specific gravity should not be too high so as to cause it to layer somewhere in the clot portion. Such layering would be of no practical use towards obtaining a separated serum portion. A preferred sealant would have a specific gravity in the range of 1.030 to 1.050.

The sealant is also preferably thioxtropic, water insoluble, substantially non-toxic as well as substantially chemically inert with respect to the constituents of the blood sample, particularly those in the serum portion.

A preferred sealant formulation is as follows:

EXAMPLE I Parts by weight The silicone fluid used in Example I was a dimethylpolysiloxane polymer made by Union Carbide Corporation and identified by the designation L- 45. it had a viscosity of 12,500 centistokes and a specific gravity of about 0.973 at 25C. The silica with a specific gravity of 2.65 was an amorphous silica having a particle size of at least 75 percent being less than 5.0 microns. It was made by Whittaker, Clark & Daniels and identified by the designation No. 31 Lo Micron". The silica with a specific gravity of 2.3 was a hydrophobic amorphous silica having an average particle size of about 20 millimicrons. It was made by Degussa Inc. and identified by the designation Aerosil R 972.

The silicone fluid and the silica were mixed together to a thixotropic condition with a resultant specific gravity of 1.045 to 1.050 to form the sealant.

The sealant was then placed in a dispenser of the type illustrated in FIG. 6 in particular. The diameter of the flange was 0.70 inches and the overall length 1.75 inches with the nozzle and tip being 1.10 inches. The opening in the tip was 0.032 inches. The filled dispenser was placed in a standard sample tube having an overall length of 3.875 inches with the shoulder 32 of the first ring resting on the top of the tube side wall. The tube had previously been filled with a whole blood specimen to within 1.10 inches of the open end of the tube. The extent of the dispenser from shoulder 32 to the end of the tip was 1.5 inches. Thus, the dispenser tip and part of the nozzle extended well into the blood sample.

The tube with the blood sample and dispenser was centrifuged for approximately 10 minutes. After 5 minutes substantially all of the sealant had passed from the dispenser. The sealant did not disperse but instead remained homogeneous and settled as a layer between the serum and clot portions of the centrifuged blood. it was noted that the sealant settled as a substantially even layer between the two portions since its specific gravity of 1.045 to 1.050 was less than that of the clot portion and greater than that of the serum portion. The sealant formed a tight seal against the inner wall of the tube. Also noted was the fact, that the sealant had mixed into it, particularly in the portion near the clot portion, fibrant matter which had been filtered out of the serum portion as the sealant settled to its own specific gravity level.

The use of the dispenser which extended into the blood sample expedited the procedure since it was not necessary for the sealant to overcome the surface tension of the blood sample.

With the sealant in place it was possible to merely decant off the serum portion with the clot being trapped behind the sealant.

The specific gravity of the sealant was determined by using a copper sulfate method. The procedure consists of letting drops of the sealant fall into a graded series of solutions of copper sulfate of known specific gravity and noting whether the drops rise or fall. The series used were graded at 0.005 intervals. Merely by observing the drops it was possible to determine that the sealant had a specific gravity between 1.045 and 1.050.

Another sealant formulation is as follows:

EXAMPLE ll Parts by weight Silicone fluid (dimethylpolysiloxane) I00 Silica (specific gravity 1.95) 14 The silicone fluid of Example 11 is the same dimethylpolysiloxane polymer of Example 1. The silica with a specific gravity of 1.05 has an average particle size of 16 millimicrons. it is made by Henlig & Co. and identified by the designation TRI-SlL 404. The specific gravity is from 1.045 to 1.050.

Still another sealant formulation is as follows:

EXAMPLE Ill Parts by weight Silicone fluid (ethyltriethoxysilane) Silica (specific gravity 2.65) 8 Silica (specific gravity 2.3) 20 The silicone fluid of Example 11 is an ethyltriethoxysilane monomer made by Union Carbide Corporation and identified by the designation A-15. The silicas are the same as those used in Example I.

The filler serves the dual purpose of making the silicone fluid thixotropic and of adjusting the specific gravity to that which is desired for the resultant sealant. In place of silica other inert fillers which may be used in a fine powdered form are bentoniate, alumina and talc. Others will also occur to those skilled in the art.

Another silicone fluid which may be used is made by Dow Corning Corporation and identified as 200 Fluid.

In selecting silicone fluids and fillers, one should select materials which when mixed together will give the desired specific gravity, be substantially non-toxic, water insoluble and substantially chemically inert with respect to the constituents of at least the serum portion.

The dispenser serves to meter out the sealant gradually and this gradual metering provides sufficient lead time for the centrifugation to take effect before the sealant is in place. If the sealant were allowed to be positioned too soon some unwanted matter, such as red cells or fibrilar like material, may be trapped in the serum portion by the sealant.

While various examples have been described herein and one embodiment illustrated on the drawings, those skilled in the art may practice the invention in its various forms by other examples and embodiments without departing from the scope of the claims herein.

What is claimed is:

1. A method of separating a sample of whole blood into serum and clot portions comprising the steps of:

placing a quantity of whole blood into a container adapted to be centrifuged;

inserting into said container a supply of a thixotropic,

water insoluble, substantially non-toxic sealant consisting essentially of a silicone fluid and an inert filler dispersed therein, said sealant having a specific gravity in the range of 1.026 to 1.092; and

centrifuging the blood into serum and clot portions until the sealant forms a'separator between said portions.

2. A method as defined in claim 1 wherein the inert filler is silica.

3. A method as defined in claim 1 wherein the sealant has a specific gravity in the range of 1.030 to 1.050.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3508653 *Nov 17, 1967Apr 28, 1970Charles M ColemanMethod and apparatus for fluid handling and separation
US3647070 *Jun 11, 1970Mar 7, 1972Technicon CorpMethod and apparatus for the provision of fluid interface barriers
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3852194 *Dec 11, 1972Dec 3, 1974Corning Glass WorksApparatus and method for fluid collection and partitioning
US3869388 *Jun 25, 1973Mar 4, 1975Continental Oil CoOil water separation
US3909419 *Feb 27, 1974Sep 30, 1975Becton Dickinson CoPlasma separator with squeezed sealant
US3919085 *Feb 27, 1974Nov 11, 1975Becton Dickinson CoPlasma separator assembly
US3920549 *Mar 18, 1974Nov 18, 1975Corning Glass WorksMethod and apparatus for multiphase fluid collection and separation
US3920557 *Feb 27, 1974Nov 18, 1975Becton Dickinson CoSerum/plasma separator--beads-plus-adhesive type
US3929646 *Jul 22, 1974Dec 30, 1975Technicon InstrSerum separator and fibrin filter
US3957653 *Apr 3, 1975May 18, 1976Becton, Dickinson And CompanyMeans for dispensing a thixotrope into the blood collection chamber
US3957654 *Jun 5, 1975May 18, 1976Becton, Dickinson And CompanyPlasma separator with barrier to eject sealant
US3976579 *Jul 10, 1975Aug 24, 1976Becton, Dickinson And CompanyNovel assembly
US3977982 *Jan 20, 1975Aug 31, 1976Corning Glass WorksControlling viscosity of silica-silicone oil gels
US3986962 *Jul 10, 1975Oct 19, 1976Becton, Dickinson And CompanyNovel assembly for separating blood
US4001122 *Aug 22, 1973Jan 4, 1977Telan CorporationBarrier, specific gravity, truncated cone
US4018564 *Nov 24, 1975Apr 19, 1977General Electric CompanySilicone composition for analyzing blood samples
US4021340 *Nov 28, 1975May 3, 1977Corning Glass WorksThixotropic, poly-butene polymer
US4043928 *Oct 31, 1973Aug 23, 1977Lukacs And Jacoby AssociatesSerum separating composition of matter
US4049692 *Dec 16, 1974Sep 20, 1977Corning Glass WorksSilicone fluid, filler, polysiloxanepolyether copolymer, thixotropic
US4052320 *Jul 8, 1976Oct 4, 1977Eastman Kodak CompanyTelescoping serum separator and dispenser
US4055501 *Jan 16, 1976Oct 25, 1977Sherwood Medical Industries Inc.Fluid collection device with phase partitioning means
US4071316 *Dec 20, 1976Jan 31, 1978General Electric CompanySilicone composition for analyzing blood samples
US4083784 *Apr 28, 1977Apr 11, 1978Corning Glass WorksStabilized blood separating composition
US4088582 *Jan 16, 1976May 9, 1978Sherwood Medical Industries Inc.Blood phase separation means
US4152269 *Feb 1, 1977May 1, 1979Warner-Lambert CompanyBlood and isolation and storage of serum; thioxotropic barriers
US4167955 *Jun 5, 1978Sep 18, 1979Beckman Instruments, Inc.Layering a liquid sample onto centrifuge tube liquid contents
US4189382 *Apr 3, 1978Feb 19, 1980Sherwood Medical Industries Inc.Blood coagulation and separation
US4190535 *Jul 10, 1978Feb 26, 1980Corning Glass WorksMeans for separating lymphocytes and monocytes from anticoagulated blood
US4235725 *Aug 16, 1978Nov 25, 1980Owens-Illinois, Inc.Polybutadiene gel barrier for testing
US4279863 *Sep 12, 1979Jul 21, 1981Sherwood Medical Industries, Inc.Reagent separator for a blood collection tube
US4333564 *Jan 16, 1980Jun 8, 1982Sherwood Medical Industries Inc.Method of controlling rheological properties of gel-like compositions
US4350593 *Jun 25, 1979Sep 21, 1982Becton, Dickinson And CompanyAssembly, compositions and method for separating blood
US4386003 *Sep 17, 1981May 31, 1983Sherwood Medical Industries Inc.Radiation-resistant gel from the gelation of a silicone oil, a silica filler, and a gel-forming; sterilization
US4534798 *Nov 18, 1983Aug 13, 1985Sekisui Kagaku Kogyo Kabushiki KaishaComposition for partitioning blood components
US4770779 *Jul 1, 1987Sep 13, 1988Terumo CorporationApparatus for separating blood
US4994393 *Feb 22, 1989Feb 19, 1991Becton, Dickinson And CompanyBlood partitioning composition
US5169543 *Mar 27, 1990Dec 8, 1992Nippon Paint Co., Ltd.Crosslinked addition-condensation copolymer dispersed in liquid copolymer; high viscosity, specific gravity, chemical resistance; barriers
US5236604 *May 29, 1991Aug 17, 1993Sherwood Medical CompanyAffinity means to attract the separated oil and prevent the interference of the separated oil with the sampling of the blood sample
US5266199 *Nov 19, 1991Nov 30, 1993Nigata Chemicals And Plastics Co., Ltd.Serum separating apparatus
US5269927 *Dec 16, 1991Dec 14, 1993Sherwood Medical CompanySeparation device for use in blood collection tubes
US5438000 *Nov 12, 1993Aug 1, 1995Nippon Paint Co., Ltd.Serum separation sealant
US5454958 *Sep 1, 1993Oct 3, 1995Sherwood Medical CompanyMethod for sampling in a container having a material therein which separates from a barrier material
US5506333 *Feb 16, 1995Apr 9, 1996Henkel CorporationSeparating blood by centrifuging
US5968018 *Oct 30, 1996Oct 19, 1999Cohesion CorporationCell separation device and in-line orifice mixer system
US5997811 *Jul 2, 1997Dec 7, 1999Cohesion Technologies, Inc.Method for sterile syringe packaging and handling
US6376210Jul 6, 1999Apr 23, 2002General AtomicsMethods and compositions for assaying analytes
US6398956May 30, 2000Jun 4, 2002Bio/Data CorporationMethod and apparatus for directly sampling a fluid for microfiltration
US6610504Apr 10, 2000Aug 26, 2003General AtomicsMethods of determining SAM-dependent methyltransferase activity using a mutant SAH hydrolase
US6740240Feb 6, 2002May 25, 2004Bio/Data CorporationMethod and apparatus for directly sampling a fluid for microfiltration
US6878346May 6, 2003Apr 12, 2005Bayer CorporationSerum transfer cup
US6926834May 25, 2004Aug 9, 2005Bio/Data CorporationMethod and apparatus for directly sampling a fluid for microfiltration
US7070939Sep 26, 2001Jul 4, 2006The Scripps Research InstituteMethods for detecting vasculopathies and tumors
US7151000 *Apr 28, 2003Dec 19, 2006The Regents Of The University Of CaliforniaSerum is treated with a complexing agent which agent binds prions in the sample forming an agent/protein complex which makes it possible to concentrate the complex
US7192729Jan 10, 2002Mar 20, 2007General AtomicsMethods for assaying homocysteine
US7288195Aug 9, 2005Oct 30, 2007Bio/Data CorporationMethod and apparatus for directly sampling a fluid for microfiltration
US7384760Apr 30, 2004Jun 10, 2008General AtomicsMethods for assaying inhibitors of S-adenosylhomocysteine (SAH) hydrolase and S-adenosylmethionine (SAM)-dependent methyltransferase
US7517694 *Jul 24, 2003Apr 14, 2009Ortho-Clinical Diagnostics, Inc.Metering tip with internal features to control fluid meniscus and oscillation
US7673758Nov 1, 2007Mar 9, 2010The Regents Of The University Of CaliforniaCollection tubes apparatus, systems, and methods
US7674388Aug 4, 2006Mar 9, 2010The Regents Of The University Of Californiaseparator tubes include curable composition with density intermediate to density of serum and cell-containing fraction; after centrifugation composition is located between serum and cell fraction and irradiated with UV light to initiate curing wherein composition solidifies to breakdown resistant barrier
US7766900Sep 8, 2005Aug 3, 2010Biomet Manufacturing Corp.Method and apparatus for application of a fluid
US7780861Jan 21, 2010Aug 24, 2010The Regents Of University Of CaliforniaPhotopolymer serum separator
US7829112May 22, 2008Nov 9, 2010The General Hospital CorporationForming two drug permeable polymeric segments, exposing to preferential drug, connecting segments, delivering drug treatment; for use in treatment of menopausal symptoms and benign ovarian secretory disorder; contraceptive
US7833545Apr 29, 2004Nov 16, 2010The General Hospital CorporationMethods and devices for the sustained release of multiple drugs
US7838024May 22, 2008Nov 23, 2010The General Hospital CorporationMulticompartment drug delivery system for use in treatment of menopausal symptoms and benign ovarian secretory disorder; contraceptive
US7883718May 22, 2008Feb 8, 2011The General Hospital CorporationMethods and devices for the sustained release of multiple drugs
US7971730Nov 14, 2008Jul 5, 2011The Regents Of The University Of CaliforniaCollection tubes apparatus, systems and methods
US8151996Aug 23, 2010Apr 10, 2012The Regents Of The University Of CaliforniaPhotopolymer serum separator
US8182769Apr 4, 2008May 22, 2012Biomet Biologics, LlcClean transportation system
US8206638Jan 21, 2010Jun 26, 2012The Regents Of The University Of CaliforniaCollection tubes apparatus, systems, and methods
US8318077 *May 29, 2012Nov 27, 2012The Regents Of The University Of CaliforniaCollection tubes apparatus, systems, and methods
US8377395Apr 29, 2011Feb 19, 2013Charles M. ColemanIntegrated blood specimen processor
US8394342Jul 21, 2009Mar 12, 2013Becton, Dickinson And CompanyDensity phase separation device
US8444620Jul 8, 2010May 21, 2013Biomet Biologics, LlcMethod and apparatus for application of a fluid
US8475742 *Nov 9, 2009Jul 2, 2013Hitachi Chemical Co., Ltd.Blood serum or blood plasma separating material and blood-collecting tube using same
US8518272Apr 4, 2008Aug 27, 2013Biomet Biologics, LlcSterile blood separating system
US8580183Nov 19, 2012Nov 12, 2013The Regents Of The University Of CaliforniaCollection tubes apparatus, systems, and methods
US8747781Jul 21, 2009Jun 10, 2014Becton, Dickinson And CompanyDensity phase separation device
US8794452Aug 1, 2013Aug 5, 2014Becton, Dickinson And CompanyDensity phase separation device
US20110250105 *Nov 9, 2009Oct 13, 2011Kunihiro SutoBlood serum or blood plasma separating material and blood-collecting tube using same
CN102872616BSep 26, 2012Oct 1, 2014成都众睿达科技有限公司一种血液分离胶及其制备方法
DE2743882A1 *Sep 29, 1977Mar 30, 1978Nippon Paint Co LtdTrennmittel und verfahren zum auftrennen einer blutprobe in serum- oder plasma- und gerinnsel-anteile
DE2820706A1 *May 11, 1978Nov 16, 1978Unilever EmeryCopolyesterzusammensetzung
EP0046391A1 *Aug 14, 1981Feb 24, 1982Sekisui Kagaku Kogyo Kabushiki KaishaComposition for partitioning blood components
EP0705882A2Sep 26, 1995Apr 10, 1996Becton Dickinson and CompanyBlood compatible, shear sensitive formulations
EP1552267A2 *May 13, 2003Jul 13, 2005Bayer CorporationSerum transfer cup
WO2003099190A2 *May 13, 2003Dec 4, 2003Bayer AgSerum transfer cup
WO2007095450A2 *Feb 8, 2007Aug 23, 2007Peter CroninImproved gel compositions, apparatuses and fluid separation methods
Classifications
U.S. Classification494/37, 494/38, 422/73, 494/23, 436/17, 210/789
International ClassificationG01N33/49
Cooperative ClassificationG01N33/491
European ClassificationG01N33/49C
Legal Events
DateCodeEventDescription
Feb 28, 1990ASAssignment
Owner name: ORGANON TEKNIKA CORPORATION, A CORP. OF DE.
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:LUKACS AND JACOBY ASSOCIATES;REEL/FRAME:005251/0338
Effective date: 19890914
Feb 28, 1990AS02Assignment of assignor's interest
Owner name: LUKACS AND JACOBY ASSOCIATES
Effective date: 19890914
Owner name: ORGANON TEKNIKA CORPORATION, A CORP. OF DE.