WO1998053314A1 - Device for determining transformed cells possibly contained in the blood of an individual - Google Patents

Device for determining transformed cells possibly contained in the blood of an individual

Info

Publication number
WO1998053314A1
WO1998053314A1 PCT/DE1998/001362 DE9801362W WO9853314A1 WO 1998053314 A1 WO1998053314 A1 WO 1998053314A1 DE 9801362 W DE9801362 W DE 9801362W WO 9853314 A1 WO9853314 A1 WO 9853314A1
Authority
WO
Grant status
Application
Patent type
Prior art keywords
device
ƒ
da
transformed cells
aphereseeinrichtung
Prior art date
Application number
PCT/DE1998/001362
Other languages
German (de)
French (fr)
Inventor
Ulrich KÜBLER
Original Assignee
Dr. Kübler GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5002Partitioning blood components

Abstract

The invention relates to a device comprising elements which are essential to repeatedly determine the presence of transformed cells and which are located in a first segment (Ch1) of the device. An apheresis device (2) and a purification device (2) arranged downstream thereto are located in a second segment of the device (Ch2a, Ch2b) which is detachably connected to the first segment of the device. The leukocytes are eliminated from the blood fractions rendered by the apheresis device. A cell identification device (10, 17) is included in a third segment (Ch3) of the device which is detachably connected to the second segment (Ch2a, Ch2b) of the device.

Description

description

Apparatus for the determination of possibly contained in the blood of an individual transformed cells

The invention relates to a device for the determination of possibly contained in the blood of an individual transformed cells after its apheretischer treatment and then optionally forming successful cultivation of thus obtained transformed cells containing blood fractions, followed by determination and evaluation of the detectable transformed cells.

It is known that transformed cells or tumor cells in an organism absiedeln from a tumor and may be in the blood stream trespassing. About the importance of circulating in the bloodstream transformed cells for the formation of metastases AJ Salsbury reports in "Significance of Circulating Cancer Cells"; William Heinemann Medical Books, New Aspects of Breast Cancer, Vol. 3, pp 245 et seq., 1977. It can circulating tumor cells in most cases, ie long before the primary tumor can be clinically proven in the bloodstream occur (PM Gullino, dev Oncol., 49, 251-271 1986.

For the treatment of tumor diseases, it is extremely advantageous if the tumorous disease is detected at a very early stage, ie before it has come to metastasize. such a tumorous disease can be diagnosed sooner, the better are the chances of recovery for the patient. In the prior art process for the isolation of transformed cells through a density gradient centrifugation are known, as they are usually used for the isolation of lymphocytes using a Ficoll gradient. However, large amounts of blood from 1500 ml of blood are required, which is very stressful for the patient. Furthermore, the apparatus required is very large, so that these methods can not be used for a routine examination. Furthermore, usually present in very low numbers tumor cells are damaged or contaminated by this conventional centrifugation.

According to the DE-Al-42 28 389 underlying process has been found that a centrifugation at

are blood sample in the arranging between the erythrocytes and the plasma layer of leukocytes, the so-called buffy coat, also abgesiedelte transformed cells of the primary tumor. In DE-Al-42 28 389 a process for the isolation and cultivation of circulating in the blood stream of an individual transformed cells is also described, wherein one by centrifugation of blood by means of a suitable for the separation of lymphocytes, continuous centrifuge or Aphereseeinrichtung a buffy coat containing the transformed cells, leukocytes and lymphocytes, takes over one of the centrifuge downstream bypass and the buffy coat cultured under multiplication of the transformed cells.

However, a disadvantage is that this method is only in

can perform installations that require a variety of individual, very time-consuming part steps that make this method not suitable for routine analysis. In addition, such systems of significant size so that its portability or her mobile use are not possible.

It is a further blood processing machine is known (EP 0771569 A2), which is equipped with a number of units which are discarded after use. These units include an apheresis centrifuge tube, inlet and outlet pipes and a manifold. This known machine has, however, no facilities, which optionally can be seen in the respective processed blood existing tumor cells or permit to be determined.

Finally, it is already a system for extracorporeal blood processing (WO 96/40322), in which a blood treatment is apheretische by which so-called "unhealthy" cells used for therapeutic purposes "healthy" cells are separated. However, the total required equipment costs are so high here that this system is neither viable, nor is suitable for mobile use. In addition, the relevant known installation is not intended for the determination of an individual's blood which may be present in transformed cells or designed.

The invention is accordingly the object of providing a small, compact apparatus which allows a simplified and fast determination of optionally contained in the blood of an individual transformed cells and that is portable and thereby allows a mobile use.

the above object is achieved in a device of the type mentioned according to the invention characterized in that the serving for repeated viable provisions of transformed cells essentially means are included in a first device section that, in a detachably connected to the first device portion second device portion has a Aphereseeinrichtung and arranged downstream of the cleaning device are housed, are in the eliminated from the processing from the Aphereseeinrich- emitted blood fractions leukocytes and containing from essentially only transformed cells blood fractions can be emitted, and that in a detachably connected to the second device portion third device section a transformed cell, if necessary is included. after their cultivation recognized and evaluated permitting cell-recognition device.

The invention has the advantage of a particularly low design effort with it, wherein by dividing the entire device in three releasably interconnected device sections or parts ensures that the one of the respectively required after use of the device cleaning required is considerably reduced and that, for others are no longer eligible for re-device parts easily reusable by

Device parts can be separated. Furthermore, the device according to the invention is readily configure so small in size and to miniaturize that leads to a very compact device which is readily portable and thus well suitable for a mobile use. It is thus particularly well as a compact charger for conducting routine investigations.

Preferably, the Aphereseeinrichtung is a centrifuge with a Durchflußrotor. This allows in an advantageous manner a continuous operation of the apparatus, so that the risk of contamination of each processed blood is minimized. At this point that the risk of contamination with bacteria, yeasts or fungi is the greater, the more processing steps to be performed manually is noted. Conveniently, an optical detecting means is connected to the Aphereseeinrichtung which containing the occurrence of transformed cells during operation of the Aphereseeinrichtung blood fraction in a particular area of

Aphereseeinrichtung determined and thereupon emits a signal that can be evaluated. Characterized which is made in the Aphereseeinrichtung separation of the so-called buffy coat from red blood cells and the blood plasma can be reliably detected in an advantageous manner. The optical detection device can comprise a light sensitive sensor, the optionally determined in conjunction with a separate light source, the light transmittance of the Aphereseeinrichtung in the above-mentioned separation and then outputs a usable signal, which can be used for the triggering of other operations.

Preferably, the Aphereseeinrichtung nachgeord- designated cleaning device comprises a capillary. This can sieve capillary preferably have a bottom size of Aphereseeinrichtung depending on the used amount of blood matched diameter with pore sizes of about 7.5 microns. arranged parallel to each capillaries are understood under a capillary bed, wherein said white blood cell fraction at the upper end of the capillary is introduced into the capillaries and is flushed under the action of gravity and by an optionally inflowing physiological solution through the capillaries. The greater the number of capillaries, the shorter is the total time for the separation of leukocytes and tumor cells or transformed cells. The length of the capillaries and their diameter may be varied readily. The expert is able at any time to adjust these parameters to the corresponding requirements.

Preferably, the capillary bed with antibodies is provided which react with antigens of leukocytes such that these are retained from the supplied from the Aphereseeinrichtung her blood fractions in the cleaning device. This has the advantage of a particularly good effectiveness of the cleaning device with them so that they practically sentlichen in WE only outputs the transformed cells. The exploited here in the capillary bed between antibodies and antigens of leukocyte adhesion effect is due to specific interactions due to van der Waals forces, hydrophobic interactions and / or ionic interactions.

It should also be noted here that also molecules of organic groups may be used in place of antibodies, specifically monoclonal antibodies and / or polyclonal antibodies, which act as affinity groups, receptors, and

Ligands, that is, in particular molecules isolated cell surface, cell adhesion molecules, lectins and glycoproteins. The best cleaning effect is achieved, however, with the aforementioned antibodies.

Conveniently, the second and third device section with a heater, a humidifier and / or a CO 2 source is provided. The isolated tumor cells or transformed cells can be maintained under optimum cell culture turbedingungen thus, that is at 37 ° C, and in a humid atmosphere, for example, 5% CO2 and 95% air.

Advantageously, the contained cell-recognition device section in the third fixture comprises a semiconductor device characteristic antibodies are bound in such a way on the individual for the transformed cells to be determined that a compound of such a transformed cell with its antigen on such antibodies, a detectable signal in the semiconductor device in question causes. This brings with it the advantage that, in a compact apparatus to be set up, a relatively simple before, but yet effective cell-recognition device is present.

Conveniently, the semiconductor device of individual transistors, in particular field effect transistors, constructed, at the base or gate electrodes that are relevant for the individual transformed cells antibodies are bound. This has the advantage of particularly easy to be established cell-recognition device with it. Conveniently, the individual transistors are each provided with only a single type of antibody. This allows advantageously to be able to speak certain transistor individually transformed cells, as these antibodies with their only form a connection with associated antibodies that can be detected.

Preferably, the antibody with their connection sites to the said transistors with gold or silver are colloidally coated. This has the advantage of a relatively simple connection of the antibodies with the semiconductor materials with them.

Reference to a drawing, the invention will be explained below in more detail, for example.

The partly schematically in the drawing, partly in section, of apparatus consists of three detachably interconnected device sections, namely an upper first device portion Chl, a thereto adjoining second device portion with the two device section parts CH2A and CH2B, and a thereto adjoining third device section Ch3. In the first mechanism section Chl, which may be formed as a virtually closed on all sides container, are the viable for repeated determinations of transformed cells serving essential means of the apparatus; these facilities are explained in more detail below. In the second mechanism section CH2A, CH2B are a Aphereseeinrichtung and one of these neighboring parent cleaning device. These facilities and the costs associated with them in the second device section übri- gen elements are usually discarded after use of the device as a cleaning too expensive, if at all possible. In the third device section Ch3 a cell-recognition device finally is housed, if necessary, to detect and evaluate the input thereto transformed cells after their cultivation permitted.

This will be discussed in more detail below. First, however, the single device sections are considered in detail.

The first device portion Chl has a filling opening 20 into which the blood which is to be processed for the presence of transformed cells is initiated. The blood passes from the fill opening 20 to a multi-way valve 1 to and is delivered at the appropriate setting of this on the output side via a line 33rd This conduit 33 has a coupling part 32, in which the rotor 21 of the Aphereseeinrichtung 2 contained in the second device CH2A portion is sealingly receivable. With the multi-way valve 1 a container 15 is connected on the input side, which contains a rinse solution and, secondly, a container 16 is connected to the multi-way valve 1 connected to the input side, containing a sterilizing agent. These two containers 15, 16, their solutions, if necessary, be used in the apparatus for cleaning purposes are, on the input side connected to a compressed air delivery line PA in each case via a valve 39 and 40 respectively. The respective valves 39, 40 are actuators, which receive supplied via separate decoders 41 and 42, control signals from a control device which will be discussed in more detail below. At this point it should be noted that even the multi-way valve 1 its necessary for each setting control signals from said control means performs conces- via a separate decoder 43 receives. On the input side the multi-way valve 1 is also connected with a container 6, in which a sterile physiological buffer solution is, if necessary, the direction section for the proliferation of transformed cells obtained in the third pre-serve. This container 6 is further connected to the output side of the input side of a further multi-way valve 4, which is on the one hand with two lines 3 and 7 and the other with a container 5 is connected to liquid waste. The container 6 mentioned above is input side connected via a valve 44 with said compressed air delivery line PA. The actuator of the valve 44 receives its control signals via a decoder 45 from the controller still to be considered. The aforementioned multi-way valve 4 receives its respective require sary for setting control signals from said control means through a decoder 46 supplied.

Of the aforementioned lines 3, 7, the line 3 is connected to the aforementioned line 33rd The conduit 7 is connected at its lower end with a coupling part 37, in the line 38 contained in the second device CH2A portion is sealingly inserted. At this point it should be noted that the first apparatus portion has a Chl indicated by two-dot chain lines comparison circuit plate on its underside by weelche the various connecting parts protrude.

In addition to the above-considered devices yet, the first device portion Chl another on the compressed-air delivery line Pa connected valve 36, the actuator is supplied with its necessary for setting control signals via a decoder 47th This valve 36 is provided on the output side with a coupling part 35, into which a associated with the Aphereseeinrichtung 2 line 34 is sealingly inserted. Furthermore, a container 13 is in the first device portion Chl also provided, which contains CO2 and whose output is connected via a valve 48 with a coupling part 50 of the first device portion Chl. The actuator of the valve 48 receives its required in each case for setting control signals via a decoder 49 of the aforementioned control device supplied. In the coupling member 50 contained in a second mechanism section CH2A tube 18 is sealingly inserted.

In addition to the above-considered devices yet, the first device portion Chl a drive device 22 for the Aphereseeinrichtung. 2 This drive device 22 receives the input side its control signals via a decoder 51 from the aforementioned control means supplied. The output side of the drive device 22 is provided with a coupling part 23, from which a portion contained in the second device CH2A drive shaft 24 is receivable.

As a further connecting elements between the first device portion and second device portions are two connector parts or the connector receiving portions to mention 31 and 71, which share with respective plug-receiving parts or plug 30 and 70 are fitted together in the second device portion CH2A and electrical connections between various devices in the first device portion Chl and allow to produce in the other device portions. Thus, a connection between an opening provided in the second device portion in the Aphereseeinrichtung 2 optical detecting means 19 and an interface circuit contained in the first device portion Chl (IF) is here made 52 through the connector with the parts 30 and 31 through which the aforementioned control means of the detecting respective 19 signals supplied can be fed. On the other connector with the parts 70 and 71 will be discussed below.

In the first mechanism section Chl already several times mentioned control device is indicated as a CPU means 53rd It is designed as a microprocessor controller having a microprocessor MP, a program memory ROM and RAM here. The microprocessor MP and the said memory ROM and RAM are connected with each other via an internal bus line system 54th This bus line system 54 includes a plurality of bus lines such as an address bus, a control bus and a data bus, and each of the bus lines has a plurality of lines, such as 16 or 32 lines. This is indicated 54 intersecting short horizontal line in the drawing by a the bus line. With the bus line 54, a transmitter-receiver module ngs UART is still connected, which is a conventional universal asynchronous working transceiver module. On this UART building block, the control device 53 is connected to an external bus line 55, which may be designed in a corresponding manner to the internal bus line 54. This is illustrated by the short horizontal lines which cross the outer bus line 55th

The above-considered external bus line 55 is connected to the inputs of the various mentioned decoder 41, 42, 45, 46, 47, 49, 51st Furthermore, a further decoder 56 is connected to the input side bus line 55th This decoder controls a display (Dis) 57, in the various displays of the device are displayed. Finally, the aforementioned interface circuit 52 is connected to the bus line 55th Via a further with the bus line 55 connected to interface circuit (IF) 58. Finally, an input device (In) connected 59 on the various inputs, for example, via buttons or selectors can be input, to cause the controller 53 m corresponding settings.

Having described the structure of the illustrated first m of the drawing device portion Chl has been explained above, will now be explained the second device portion with its two parts and CH2A CH2B. The above-mentioned Aphereseeinrichtung 2 is connected on its underside with a bevel gear comprising conical wheels 26, 27, 28 and 29 with the drive shaft 24, the processing of the Antriebseinπch- 22 here can be driven. The bevel gear is accommodated m a bugelformigen bearing part 25 which is in turn connected to a partition wall 60 between the two processing sections share Vorπch- CH2A and CH2B. On the upper side, the Vorπchtungsabschnittsteil a CH2A

Cover plate 61, through which the various lines and drive tubes can be seen to pass therethrough to be received at the bottom of the first Vorπchtungsteiles Chl of appropriate couplings or recordings.

In the lower portion CH2b of the second device portion is a capillary 8 which is coated with antibodies (indicated in the left part by transverse Y-mark), which in such a way react with antigens of leucocytes, that these out of the Aphereseeinrichtung 2 zugefuhrten blood fractions are retained m the capillary bed 8 via the lines 33, 3, 7 and 38 forth.

In the lower portion CH2b of the second device portion is still a heater 14, Ch3 is effective, moreover, for the third device section, and there it terminates the line 18 connected to the CO 2 ~ source 13 for the introduction of CO 2 "gas. Further, is in the lower part of the second device portion nor a line 11 Exists, from the third device section Ch3 liquids, such as the physiological solution can be discharged via which have been introduced in this section. in the lowermost device section Ch3 finally there is a cell-recognition device, to which in the present case, a semiconductor device 10 is one which can be made up of individual transistors or field effect transistors, which are carried by an insulating support 17th with the base or gate electrodes of the transistors in question are for the single transformed cells relevant antibody bound, which by small hooks in the lower part is indicated ren the drawing. Together with their other electrodes such as source and drain electrodes, the respective transistors are connected to a voltage source and arranged in such a basic circuit that a Spannungsbzw. Change in potential at the respective gate electrode leads to a detectable change in voltage at the output electrode in question. With their output electrodes, for example with their drain electrodes, the respective transistors to the input side of a multiplexer 62 are connected, which is connected by its control input 63 to the bus line 55 and receives supplied via this bus system from the control means 53 control signals necessary to set. With a signal output of the multiplexer 62 via an amplifier (A) 64 and a subsequent analog-to-digital converter (ADC) 65 (IF) connected to the input of an interface device 66, whose output is also connected to said bus line 55, and this of the control device 53 can be queried. between the first connecting portion and second connecting portion Chl CH2A, CH2B is used to ensure this compound thereby provided connectors 70, 71. The above-mentioned bus line 55 in this case runs within the second and third device section by a protective pipe 67th

When provided in the previously considered cell recognition device semiconductor device or docking of transformed cells with their antigens to the bound to the individual transistors associated antibodies in the case of Anbin- dens, a potential change caused when the respective transistors so that it via the multiplexer that serves as a selection switch, and the downstream amplifier as a first analog signal can be seen that as a digital signal in the control device 53 is evaluated by the aD conversion in the analog-digital converter 65 and the display device 57 for providing a corresponding display can be used.

Above, the three sections of the device apparatus have been considered in more detail according to the invention. In this case, it has been stated that this device section are detachably connected together. With respect to the second and third portions device CH2A, CH2B and Ch3 is indicated by means of screws 12, with which the two parts of the device are detachably connected together. With respect to the first device portion Chl and second Vorrichtungsab- section CH2A, CH2B this is indicated in the drawing by clamping closures, among those connected to the device section Chl clamping bracket 68 and with the second device portion CH2A, CH2B associated clamping noses 69th By releasing the clamp 68 by the lock tabs 69 so-can with which the serving for repeated viable provisions of transformed cells essentially means of the device mechanism section containing or are parts by detached from the rest of the device sections or parts by and after cleaning of the multiway valves and the connected to these lines, blood is passed through in the course of an application of the device in question can be used again.

The other two sections device CH2A, CH2B and Ch3 be discarded in principle, as they are no longer usable for re-applications of the present device. but they can also be separated from one another, of the Third te device section Ch3 can be concerning the information contained on it transformed cells further study. This is particularly useful in the case that the cell-recognition device also has a cell culture plate in which the transformed cells were able to proliferate.

Finally, the essential operation of the above-described embodiment of the device according to the invention will be briefly considered. First, the to be examined blood via the inlet opening 20 and the multi-way valve 1 enters the apheresis device 2. If the Aphereseeinrichtung or bell 2 is completely filled with blood, the multi-way valve 1 is blocked by or to the inlet port 20. The Aphereseeinrichtung is then treated with, for example, 4800 min -1 in rotation. Characterized initially, then flows plasma, which is the lightest blood component through the lines 33 and 3 to the multi-way valve 4 back down, that is open in this case the container 5, so that there the plasma can be collected. Unless further trifugiert cen- turn aside from further fractions from the bell and can be collected in the container. 5

At the upper periphery of the small Aphereseeinrichtung 2 of the buffy coat rises, which is detected due to its lower light transmittance now by the optical detecting means 19, which thereupon emits an analyzable by the control means 53 signal. The controller 53 then causes the multi-way valve 4 is opened from the line 3 to the line 7 back, so that now under the effect of the valve 36 and the discharge of compressed air into the conduit 34 of the buffy coat from the Aphereseeinrichtung 2 by the lines 33 , 3, 7 and 38 may be dispensed in the capillary bed. 8 If it is determined by the optical detecting means 19, that the entire buffy coat is removed from the Aphereseeinrichtung 2, the multi-way valve 4 is closed again.

Claims

Patentanspr├╝che
1. A device for the determination of possibly contained in the blood of an individual transformed cells after its aphereti- shearing treatment and if necessary forming anschließend success of cultivation obtained by transformed cells included- blood fractions, followed by determination and evaluation of the detectable transformed cells characterized in (Chl) daß in a first device section für repeated durchführbare provisions of transformed cells serving essentially means are included in a daß with the first mechanism section (Chl) connected lösbar second mechanism section (CH2A, CH2B) are housed a Aphereseeinrichtung (2) and arranged downstream of the cleaning device (8) in the output from the from the Aphereseeinrichtung (2) blood fractions
Leukocytes are eliminated and containing from essentially only transformed cells are dispensable blood fractions, and daß in a device with the second portion (CH2A, CH2B) lösbar associated third device portion (Ch3) a transformed cells, optionally after culturing them recognized and evaluated permitting cell Erkennungeinrich- device (10) is included.
2. Device according to claim 1, dadurchgeken nz eichnet that Aphereseeinrichtung (2) daß a centrifuge (2) with a Durchflußrotor umfaßt.
is 3. A device according to claim 1 or 2, e denotes dadurchg, da├ƒ with the Aphereseeinrichtung (2) an optical detecting means (19), which blood fraction containing the occurrence of transformed cells during operation of the Aphereseeinrichtung (2) in a certain determines the area of ​​Aphereseeinrichtung (2) and thereupon emits a signal that can be evaluated.
4. The device according to one of Ansprüche 1 to 3, d a- through in the daß the Aphereseeinrichtung (2) downstream of the cleaning device (8) enthält a capillary bed.
5. Device according to claim 4, dadurchgeken nz eichnet, the capillary (8) provided with da├ƒ Antik├╢rpern is that react with antigens of leukocytes such these da├ƒ from the Aphereseeinrichtung (2) her zugef├ ╝hrten blood fractions are retained in the cleaning device (8).
6. Device according to one of Ansprüche 1 to 5, ch dadur in daß the second and third device portion (CH2A, CH2B; Ch3) with a heater (14), a humidifier and / or a Cθ 2 ~ Quellle (13) are provided.
7. Device according to one of -Anspr├╝che 1 to 6, ch dadur in da├ƒ in the third Vorrich- line section (CH3) given cell recognition means (10) umfa├ƒt a semiconductor device to which individual f├ ╝r the transformed cells to be determined characteristic Antik├╢rper are attached in such a way da├ƒ a compound of such a transformed cell with its antigen on such Antik├╢rper a detectable signal in the relevant semiconductor device causes.
8. Apparatus according to claim 7, dadurchgeken nz eichnet, the semiconductor device daß of individual transistors, in particular field effect transistors is constructed, at the base or gate electrodes of the relevant für the individual transformed cells Antikörper are bound.
9. Apparatus according to claim 8, dadurchgeken - draws individual transistors daß only with a single type of Antikörpern are provided.
10. The apparatus of claim 8 or 9, dadurchg ek ennzeichnet that Antikörper daß with their conjunction steep to said transistors with gold or silver are überzogen colloidal.
PCT/DE1998/001362 1997-05-16 1998-05-16 Device for determining transformed cells possibly contained in the blood of an individual WO1998053314A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DE1997208743 DE29708743U1 (en) 1997-05-16 1997-05-16 apheresis
DE29708743.6 1997-05-16

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE1998223979 DE29823979U1 (en) 1997-05-16 1998-05-16 Means for determining, optionally contained in the blood of an individual transformed cells

Publications (1)

Publication Number Publication Date
WO1998053314A1 true true WO1998053314A1 (en) 1998-11-26

Family

ID=8040457

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1998/001362 WO1998053314A1 (en) 1997-05-16 1998-05-16 Device for determining transformed cells possibly contained in the blood of an individual

Country Status (2)

Country Link
DE (2) DE29708743U1 (en)
WO (1) WO1998053314A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6423688B1 (en) 1997-07-31 2002-07-23 Athena Neurosciences, Inc. Dipeptide and related compounds which inhibit leukocyte adhesion mediated by VLA-4

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4832034A (en) * 1987-04-09 1989-05-23 Pizziconi Vincent B Method and apparatus for withdrawing, collecting and biosensing chemical constituents from complex fluids
DE4228389A1 (en) * 1992-08-26 1994-03-03 Kuebler Gmbh Dr Obtaining and culturing transformed cells and producing antibodies directed against them
WO1994025086A1 (en) * 1993-04-27 1994-11-10 Haemonetics Corporation Apheresis apparatus and method
WO1994027698A2 (en) * 1993-05-28 1994-12-08 Baxter International Inc. Continuous centrifugation process for the separation of biologic components from heterogeneous cell populations
US5391272A (en) * 1992-03-06 1995-02-21 Andcare, Inc. Electrochemical immunoassay methods

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4443345A (en) * 1982-06-28 1984-04-17 Wells John R Serum preparator
CA2218899A1 (en) * 1995-06-07 1996-12-19 Edward V. Cruz Extracorporeal blood processing methods and apparatus
US5769811A (en) * 1995-10-31 1998-06-23 Haemonetics Corporation Blood-processing machine system

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4832034A (en) * 1987-04-09 1989-05-23 Pizziconi Vincent B Method and apparatus for withdrawing, collecting and biosensing chemical constituents from complex fluids
US5391272A (en) * 1992-03-06 1995-02-21 Andcare, Inc. Electrochemical immunoassay methods
DE4228389A1 (en) * 1992-08-26 1994-03-03 Kuebler Gmbh Dr Obtaining and culturing transformed cells and producing antibodies directed against them
WO1994025086A1 (en) * 1993-04-27 1994-11-10 Haemonetics Corporation Apheresis apparatus and method
WO1994027698A2 (en) * 1993-05-28 1994-12-08 Baxter International Inc. Continuous centrifugation process for the separation of biologic components from heterogeneous cell populations

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6423688B1 (en) 1997-07-31 2002-07-23 Athena Neurosciences, Inc. Dipeptide and related compounds which inhibit leukocyte adhesion mediated by VLA-4

Also Published As

Publication number Publication date Type
DE29708743U1 (en) 1998-09-17 grant
DE29823979U1 (en) 2000-03-16 grant

Similar Documents

Publication Publication Date Title
Raidt et al. Cellular events in the immune response: analysis and in vitro response of mouse spleen cell populations separated by differential flotation in albumin gradients
Hunninghake et al. Pulmonary sarcoidosis: a disorder mediated by excess helper T-lymphocyte activity at sites of disease activity
Boyum Separation of lymphocytes, lymphocyte subgroups and monocytes: a review
Dustin et al. Anchoring mechanisms for LFA-3 cell adhesion glycoprotein at membrane surface
Vos et al. Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis
Reinherz et al. Abnormalities of T cell maturation and regulation in human beings with immunodeficiency disorders.
Cupps et al. Suppression of human B lymphocyte function by cyclophosphamide.
Brooks et al. IL‐1β production by human polymorphonuclear leucocytes stimulated by anti‐neutrophil cytoplasmic autoantibodies: relevance to systemic vasculitis
Cabrera et al. Analysis of HLA expression in human tumor tissues
Hall et al. The cellular basis of allograft rejection in vivo. I. The cellular requirements for first-set rejection of heart grafts.
US4708714A (en) Apparatus for the separation of fractions from body fluids
Wisløff et al. Antibody‐dependent lymphocyte‐mediated cytotoxicity in man: no requirement for lymphocytes with membrane‐bound immunoglobulin
Jourdan et al. The myeloma cell antigen syndecan‐1 is lost by apoptotic myeloma cells
Kamisago et al. Role of sulfatides in adhesion of Helicobacter pylori to gastric cancer cells.
Brown et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury
Sheibani et al. Antigenically defined subgroups of lymphoblastic lymphoma. Relationship to clinical presentation and biologic behavior
Grosser et al. Tube leukocyte adherence inhibition assay for the detection of anti‐tumour immunity. I. Monocyte is the reactive cell
US6596500B1 (en) Binding of retinoids to M6P/IGF-II receptor
US7232653B1 (en) Cancer cells from body fluids containing cells, isolation thereof and agents containing the same
US5648223A (en) Methods for enriching breast tumor cells
Farid et al. A study of human leukocyte D locus related antigens in Graves' disease
US5336760A (en) Method and useful apparatus for preparing pharmaceutical compositions
Wallis et al. Human monocyte adherence to cultured vascular endothelium: monoclonal antibody-defined mechanisms.
Warren et al. Possible association of the exetended MHC haplotype B44-SC30-DR4 with autism
Brown et al. Cell surface markers for human T and B lymphocytes

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase in:

Ref country code: JP

Ref document number: 1998549802

Format of ref document f/p: F

122 Ep: pct application non-entry in european phase