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2) United States Patent oy oy m 0) ey @ (66) wr 63) G0) Aug. 19, 2014 on Lundquist et al. CENTRIFUGE AND METHOD OF CENTRIFUGING A BLOOD SAMPLE, Applicant: RE PPLIX APS, Birkerod (DK) Inventors: Rasmus Lundquist, Bronshoj (DX), Nells Erik Holi, Birkerod (DK) REAPPLIN APS Assignee: (8) Notice: Subject to any disclaimer, the teem ofthis patent is extended of adjusted under 35 USC. 1544b) by 0 days. Appl. Nox 181804,370 PCT Filed: Aug. 19, 2015 PCT No, $371 (eX!) (2) Date: PCTIBP2015/069067 Feb. 16, 2017 PCT Pub, Nos WO2016/026901 PCT Pub. Date: Feb. 28, 2016 Prior Publication Data US 201710252452 Al Aug. 17, 2017 Foreign Application Priority Data ey 14181377 Im C1, Boi 04 AGIM 136 Bode 13700 (2006.01) (2005.01), (2006.01) BOAR 5/0421 (2013.01): AGIM 13693 (2013.01); BOs 13/00 2013.01): 461M 2208/3306 (2013.01); BOA 20137006 (201301) US 10,493,467 B2 Dee. 3, 2019 USO 1049346732 (10) Patent No.: (4s) Date of Patent: (58) Fleld of Classification Seare CPC... BOAR 5/0414; BOSE 10421; BOAB 13/00 "BOAT 2013/0065; A6IM 1/3693; 461M 2205/3306 See application file for complete search history. 60) References Cited US. PATENT DOCUMENTS B6T4I96 A+ TI9T2 Phere oan sos 2174 AI6GO8 A NI9EK. Migasi (Coutinved) FOREIGN PATENT DOCUMENTS wo 200132280 AL 52001 (OTHER PUBLICATIONS International Search Autbo,ity International Seach Repost PCT 20181069067, dated Feb. 25,2016 (Continsed) Timothy C Cleveland Luedeka Neely Group, Primary Examiner (74) Attornes, Agent, or Firm Pc 6 ABSTRACT A centrifige comprising a rotor having a rotational axis, at least one roeptacle fora blood sample container, contraler ‘means for controlling the rotational speed of the rotor, at least one optical transmitter for transmitting an optical signal, at Jeast one optical receiver for registering, the amplitude of the optical signal, where the optical signal is configured to pass through the blood sample container where the optical receiver detects the amplitude of the optical signal wien it is directed throvgh the blood sample con- ‘ainee, where the amplitude of the optical signal relict the transfucency of the blood sample, where the controler eas is configured to discontinue the rotational movement ofthe rotor when the amplitude of the optical signal over (Continved) US 10,493,467 B2 Page 2 {ime has fulfilled a predefined pattern indicating that atleast the fibrin compression pase ofthe blood sample is tated. 19 Claims, 3 Drawing Sheets 66) References Cited USS. PATENT DOCUMENTS, ATTIAL A 101988 Cate at a 7a3w57 Bz 102008 Hlavinka ta 8236184 B2 82012 Holmes eal. 538210 B2 92013 Kolenbrander ea 980301 B2 42015 Lundgu eta 20190140226 AL 62013 Conduite a. dowwoost771 AL 22014 Case etal (OTHER PUBLICATIONS Inferational Seach Authority Wien Opinion PCT/EP2018 069067, date Ju. &, 2016 * cited by examiner U.S. Patent Dee. 3, 2019 Sheet 1 of 3 US 10,493,467 B2 B . it I a 3" Figt 5 6 A ee ‘ 10 , 8 —— 8 t sss Fig.2 US 10,493,467 B2 Sheet 2 of 3 Dee. 3, 2019 U.S. Patent Fig.3 Abaeanae one apn fe Fy i g dg | henmaibintatndaniindtitindatnwicnccl a 8 Fig.4 U.S. Patent Dee. 3, 2019 Sheet 3 of 3 US 10,493,467 B2 Fig.5 vossiasuess % ere tin) US 10,493,467 B2 1 CENTRIFUGE AND METHOD OF (CENTRIFUGING A BLOOD SAMPLE RELATED APPLICATION ‘This application claims priority to PCTIEP2015°069067, filed Aug. 19, 2015. FIELD OF THE INVENTION A centrifuge and method of controlling a eentefige ‘comprising a rotor having a rotaGonal axis, at least one receptacle fora blood sample container, controler means for ‘controlling the rotational speed of the rotor, at least one ‘optical transmit for tansmiting an optical signa, atleast ‘one optical receiver for registering the amplitude of the ‘optical signal. BACKGROUND Jn modern medicine there is an increased tendeney in Utilizing elements from blood inthe treatment of silments or {or disgnostie use. One method of extracting elements from blood such as thrombocytes (platelets), leukocytes (white blood cells) or blood plasma is by fractionating whole blood by placing a container of whole blood ia a centeifuge where the blood becomes separated into its component pats “The component parts may be ullized for specific twat- mentor diagnostic purposes forthe human bods, where the specific components may be administered to a patient that might neod a dosage of thrombocytes, in ease that patient ‘does not have enough thrombocytes in case of a hemor. rhage. Another se forthe component parts of whole Blood ‘may e.g hein wound treatment, where the whole blood msty be introduced into a container wre the blood is induced ‘coagulate and where upon a specific centrifugation regime the components ofthe whole blood have been concentrated Ito a blood product. ‘WO 20101020254 discloses how to prepare a muli= Iayered blood product by centrifugation of blood, where the blood is placed in @ container and the coagulation of the blood is activated during or after placing the blood in the container. During the centrifugation, the components ofthe blood ae separated from each other and produce a theee- layered blood produc, which in sequential order comprises 2 first Layer, which substantially comprises fibrin, a second, ‘intermediate layer, which substantially compises thrombo- cytes, and a tied layer, which substantially comprises Teukocytes. ‘WO 20121037942 discloses container to be used for preparing 2 multi-layered blood product by centrifugation ‘where ssid container comprises a filing opening as well as ‘iter device which is slidable inside the contsiner. The fiker device comprises a planar mesh and a supporting buoyancy body, where the filter deviee is adapted o collect the multi-layered blood product on o above the mesh, In WO 2010020254 ‘and WO 2012/087942 there is 9 requirement thatthe whole blood and/or the contsiner hold- Jing the whole blood has to be cenrifiged a certain amount ‘of time at certain speed in order to ensure thatthe blood, product has been formed inside the container "However, sone ofthe important factors forthe provision ‘of the blood product is the coagulation ofthe whole blood inside the container, it has beon observed that the eoogula- tion time of whole blood may vary significantly from one donor to another. This variation in coagulation fine affects the centrifugation process of the container holding the whole 0 o blood, as the preparation time of the blood product may diller considerably fo two diferent blood donors. It is also to be recognised that other factors, such as age, medica. ‘ments, diet and health of the donor ean affect the preparation time of the blood product using a centrifuge. "Ths, the medical professionals tha are preparing a blood product, such as the blood peoduet disclosed in WO 2010) (020284, do not have any methods for determining the exact Amount of time that is necessary at certain speed fo ensre that the blood product is ready for use for wound ealing, prior tothe centrifugation process “The centrifugation process of the blood produc is often performed using a benehtop of a table centrifuge that is provides with rotor that rotates along a vertical axis, where the containers are arranged in a radial direction away from the rotational axis, The containers are offen either fixed at a certain angle, or they may be arranged to be positioned at fone angle to the rotational axis when the rotor i stationary and to rotate in # direction towards plane that is perpen- ‘cular to the rotational axis when the rotor has boca fccelerated into rotational motion, ie. swinging head cen- ‘elles or swing-out (buckets) centrifuges. Such rotational ‘movement ofthe container ensures that he centrifigal force {uring centrifugation may be directed along the longitudinal axis ofthe container, ensuring thatthe particles density of the particles inside the whole blood isin sequential onder, ‘where the particles having a higher density is at a distal end of the container, while the particles having smaller densities fare concentrated at a more proximal position in the con- tainer. The tems proximal and distal defined in relation to the rotational axis of the centrifuge, where the distal end of the container isthe part of the container that is arranged father away from the rotational axis during centrifugation, while the proximal end is arranged closed to the rotational FFor safety reasons, « benchiop or @ table evutrfuge is provided witha lid, so thatthe rotating motion of the rotor cannot injure or harm any persons that are in the vicinity of the cenrfige during operation. Thus, this often means that the blood samples or the whole blood inside the container cannot he inspected during centrfgation, as there is no direct visual access tothe content of the container. Furtber- more, asthe centrifuges can operate ata rovational speed that may be up to 4000 RPM, 8000 RPM or more, i. appeoxi- rately 66-132 revolutions per second or more, it may be dificult or even impossible 10 visualise the state of the contents of the container during rotation with the bare eyes ‘even if here wold be direct visual acess to the eontenis oF the container. ‘Furtermore, 28 coagulation occurs over a certain period of time, where the termination ofthe coagulation is indicated by the lack of change in optical density the proces has t0 be observed continuously during the process in order to get the optimal result of the coagulation process "Ths, the medial professionals preparing a blood product do not have any methods or tools to recognise when the centrifugal process of the container has been carried out enouigh to prepare the blood product suficiently for use. Ths, the melcal professionals have ted to figure out a amount of time that is suficient for most users, and apply ‘his qualified guessed amount of time to the centrifugal process. Asan example, ifthe predetermined amount of time 5s 10 minutes, his amount of time may be suficient far some donors, while for other donors the blood has 1 be reintro- ‘duced to the central process after removing the container from the centrifige and visually inspecting the contents. Por some donors, the blood product may be ready within 2-S US 10,493,467 B2 3 minutes, while for other donors the blood product may’ be ready within 15-20 minutes oF even more, of the inital ‘centrifugation. Thus, if it is ncessary o prepare multiple blood products forthe wound treatment of a daaor, each minute of Wasted ‘centrifugation andor visal inspection may be multiplied by the amount of products to be prepared by subsequent cen- teifugation processes. Ths, there is need to increase the cllciency ofthe centrifugal process. GENERAL DESCRIPTION In accondance with the invention, there is provided a centrifuge comprising a rotor having a rotational axis, at least one receptacle Jor blood sample container having & travitatioal axis, where the receptacle comprises atop end Jor receiving a blood sample container and bottom end for holding the blood sample contsiner, where the receptacle is ina position tht is at an angle tothe rotational axis of the ‘centrifuge, where the centrifugal force extends from the top ‘eu ofthe receptacle towards the bottom end of the recep twele, controller meuns for controling the rotational speed oF the rotor, at least one optical transmitter for transmitting an ‘optical signal in a divection that is at an angle 10 the rvitational axis of the receptacle and through an upper phase andor the plasma of a blood sample in the blood sample container, a least one optical reeiver for registering the amplitude ofthe optical signal, where the optical signal js configured to he directed towards the blood. sample ‘container where the optical receiver detects the amplitide of the optical signal, where the amplitude of the optical signal reflects the transhicency af the upper phase andlor the plasma of the blood sample, where the controller means is ‘configured to discontinue the rotational movement of the rovor wen the amplinud ofthe optical signal overtime has fulfilled a predefined pattern, indicating that at least the fibrin polymerisation phase of the blood plasma is started. "The measurement of the translucency of blood is 3 relative factor, depending on the choice of optical transmit- ters and optical receivers, 25 well as the material ofa blood sample container. Ths, in relation tothe present invention, the amplitude of optical signal is considered asa represen. tation ofa relative translucency where the measurements are ‘adapted to detect the change in translucency over time ofthe blood sample. The optical transmitter may be a LED based transmitter, a laser diode, where a light at a suitable wave- Jength may be directionally emitted towards an optical receiver. The optical receiver may be a photodetector, such a8 pon photodiodes, p-inn photodiode, avalanche photodiode ‘or any type of photodetector that is capable of registering and differentiating the amplitude ofthe received light. “The centrifuge may be of the kind where the reeptacle may be adapted to move from a position where the gravi- tational axis is substantially parallel to the rotational axis of the contrfige to position that is substantially perpendica- Jar tothe rotational axis ofthe centrifuge. The centrifuge may thus be a bucket centrifuge having a swinging. bucket (receptacle) o may be a fixed angled centefvge, where the bucket (receptacle) may be fixed ata certain angle relative 1o the rotational axis of the cent, ‘The angle of the receptacle jn relation tothe rotational axis of the centrifuge may be between 30° and 9". Tt has ben shown that a preferred method of centrifuging may be where the receptacle is at a 90° angle relative 10 the rotational axis, or where itis substantially perpendicular to the rotational axis. Some centrifuges may have a receptacle 0 o 4 where the recepiace is at fixe angle, where the angle may be anywhere between 30° and 90° ‘The centrifuge in aoeordance with the preseat invention may bea rotational centrifuge that provides centrifugal force Tr the sedimentation of whole blood by increasing the aravitational force that is applied toa container comprising ‘whole blood. The rotor of the centrifuge may’ be adapted 10 put the receptale in rotation around a ixed axis, so thatthe centrifugal foree is applied perpendicular o the fixed axis, The receptacle may be hinged inside the centrifuge, so that the receptacle is ina substantially vertical position (parallel ‘o te fixed axis) when arrested and during centrifwpation the receptacle will tlt towards a substantially horizontal posi ‘ion (perpendicular tothe fixed axis). Thus the longitudinal axis ofthe receptacle and/or the blood sample eontsiner may be substantially perpendicular tothe fixed axis during cen- ‘ellgation, so that the centeifugal forve is applied in a rection parallel to the longitudinal axis of the receptacle andor the blood sample container. Alternatively, the cen- ‘rfigal force may be applied ina direction that iat an angle to the longitudinal axis of the blood simple container, where the angle may be between about 1* and 60° degrees. “Thus, the eentifal Torce may be seen as being in a iretion that extends ina direction away from the rotational fais of the centrifuge so that the gravitational force frst intersects the top of the blood sample container andor the receptacle and subsequently intersects the Bottom of the blood sample container andlor the receptacle. This means that the top of the receplaclecomtaner is closer to the ccatrfgal axis of the centrifuge than the bottom of the ‘container, which means that the eentefal force forces the ‘blood separation ina direction from the top ofthe container! receptacle towards the bottom of the containerreceptale Hence, the gravitational fckd, which is applied by the ceatrifyge fo the receptacle andor the container is lower in the area of the containerreceptacle that is closer to the rotational axis, i in the top nl ofthe contsinerreceptacle, than itis in the area of the contsneriroveptale that is distant to the rotational axis, i. in the botiom end ofthe container! receptacle, The grivitational field may be ealeulted using the following formule er essen ‘where RCF is the rotational eentrifigal force, Ris the radius ff rotation (measured in millimetres) and RDM is the rotational speed ofthe centrifuge. Within the meaning of the present invention, the upper part of the container may be a part of the container that is proximal wo the liked axis ofthe centrifuge during centefi- {ition while the ower part of the container isthe par of the feantiner that is distal to the fixed axis ofthe eentifige. ‘During centrifugation of the whole blood into a blood radi, the phases of the blood fractionation may comprise the following phases when the blood sample is being cen- ‘iluged: Separation of blood. This may be seen as the initial separation of blood ino its components, where the twlole blood separates into a clear solution of blood plasma in the upper part of the container, an intermit- tent part of a buffy cout comprising leveaeytes and platelets, and erythrocytes at the bottom of the con- Tniner as the erythrocytes have a higher density than leueoeytes and the platelets. In this phase, the blood US 10,493,467 B2 5 plasma comprises fibrinogen monomers. This separa- tion may be seen in three phases where the separstion may be seen asthe separation of eukoeytes, separation of platelets Fibvin polymerisation, where the fbrinogen monomers polymerize end to end 4 form protfirils which asso €iate laterally to oem fibrin fibres. The fibrin polymer Sation phase inthe blood plasma causes the transhae ency of the blood plasma to decrease asthe fibin is formed Fibvin compression, when the fibrin polymerisation is complete, the fbr fres inside the plasma begin to Ccampress on top of the thromboeytes due to the cen= ‘wifgation, and the translucency of the blood plasma begins to increase Clearing of other plasma components, inthis phase, the fibrin compression hss been completed and other compo- rents inthe plasma begin concentrate causing the trnshi- ‘eeney ofthe blood plasima to increase even further. The other ‘components may include particles, cells and molecules, such 2 fat fibrin, fibrinogen, or any other components that are in the blood plasm and will clear during the centrifugation “The separation of blood may be seen ass process where the separation is intended to separate different parts ofthe Blood into separate areas ofthe container. The separation may be the separation of erythroeytes, the separation of leucocytes and the separation of plielets, where the three separation phases ofthe process may be identified using measurements ttlizing optical signals tht are directed through part ofthe ‘whole blood, Each of the above phases ofthe blood fctioning can be recognized using a measurement of the translucency of the blood plasma, where certain changes in the translucency patter during substantially constant ceneifugation process Indicates the shit from one phase to its subsequent phase ‘The optical transmitter may be adapted to transmit the ‘optical signal, where the optical receiver is adapted t0 measure the amplitude of the signal on a predefined scale. ‘The optical signal passe through the Blood sample container and ifthe optical signal is intersected by components in the liquid pants optical signal will diffuse duc to the intersction, and only parts of the optical signal will pass throng the container to be received by the optical receiver, and the ‘amplitude of the signal will be reduced on the predetined cule, As the optical signal is registered over time itis possible to monitor whether the clarity of the Tguid inside the container i constant, increasing or decreasing relative t0 the predefined seale “The controller means may be adapted to receive an input from the optical receiver, so that the amplitude of the optical signal may be utilized to control the rotational sped of the centrifuge. ‘The contoller means may comprise a signal, ‘comparator, so that when a certain threshold, pattern oF tendency ofthe signal is observed by the controller means, the controller means will adjust the rotational speed of the ‘centrifuge by controlling the current oF the voltage of the ‘eleczial signal that is sent to the movor of the eentfge The controller means may be in the form of a mieroprocess sor, microcontroller, being capable of receiving electrical signals transmitted from the optical receiver, processing the signals received and performing certain operations based on the electrical signals received by sending out output signals ‘© contol the rotational movement of the centetige, ‘The centrifige may be configured so that the optical signal is directed to pass through an upper part of the ‘container, so thatthe optical signal passes tough the blood plasma during the initial separation of blood. This means 0 o 6 that the amplitude of the optical sina is capable of regis tering when the components (bully coat and erythrocytes) ia the whole blood ae forced towards the bottom of the ccntainer de tothe eentrifgalforees during centrifugation. ‘Thus, by transmitting the optical signal into an upper part of the container the amplitude difference between the clear blood plasma and the whole blood is maximized, allowing ‘maximal variation in the amplitude of the optical signal. Should the optical signal be transmitted through the lower part of the container the transmission through the whole blood would commence through an opayue part ofthe blood sample and the transmission ampliude would decrease during the inal blood separation phase, asthe bully coat ‘and the erythrocytes would shift towanls the bottom of the container eausing the liquid to become more opaque. Thus the amplitude variation would be reduced, which could cause a reduced reliability of the measurements compared 10 ‘a measurement that passes through the upper part. Such 3 ‘measurement could be performed, and a pattem for the separate phases could be ideaified, but dhe reliability of « ‘measurement in the upper partis sen as being greater, asthe variation inthe opaqueness and/or transparency of the iguid is greater Alternatively, the optical signal may be a light source that ithuminates the container, whore the optical receiver may be in the form of a camera that is capable of registering the amplitude of the light reflecting olf the container, so that ‘when the liguid is translucent the amplitude of the optical signal received by the eamera is low, where the optical siznal increases when the translucency of the plasma is reduced. Thus, in such a measurement the amplitude of the ‘optical signal may be inverted in view of in an embodiment ‘where the optical signal passes through the container. Thus the patiem of the amplitude may be obtained by image analysis or image processing ofthe signal obtained by the ‘ame, such as Feature extrction, The eamera may’ obtain continuous or discrete images that are fed into a pattern recognition software that may be part of the coattoller oF ‘working in conjunction with the controler Thus, by continuously registering the amplitude of the ‘optical signal over time itis possible to monitor the cen- ‘elation process in order to asses in what state the blood sample isin ata given moment in time. When the signal as Tollowed » predefined patter itis possible to determine that the blood sample is ia a desired state, allowing the blood product to he collected from the blood sample container ‘Thus, the centrifugation may be stopped when the blood sample has reached is desired phase of blond! fractionation ensuring that the centrifugation is not discontinued prior to the desited phase or that the centrifugation is not eared longer than necessary. The predefined pattem may be defined by analysing the signals From severl individual patients, where itis possible by tial and error to find similar pattems in the optical detection which indicates that the atleast brn compression phase is stated. Purbermore it may be possible to monitor the signal Hive fon a graph, which allows the professional to analyse the Signal to find the correct time when the coagulation andor blood fractioning has reached a level that is enough to form ‘ blood production. “The eentrifgation may be continued beyond the prelimi nary part ofthe fibrin compression phase, in order (0 ensure that all the fibrin has been compressed in the lower part of the container, The amplitude of the optical signal in the ‘upper part of the container will decrease during fibrogen polymerisation phase, as the fbrogen molecules bond with US 10,493,467 B2 1 ‘each other and cause the plasma fo be more opaque during the polymerisation phase. Subsequently, when the fibrogen polymerisation is finished, the fibrin begins to compress ia the lower part ofthe container, causing the amplitude of the ‘optical signal to inerease during the fibrin compression Phase, as the polymere frogen (Bibrin) is cleared tm the blood plasma. The centrifugation may futher be continued into the clearing of plasma components phase which super sees the fibrin compression phase, a the amplitude of the ‘optical signal is increased even lure as the componcats in the plasma move towards the bottom of the container due 10 the centrifugal force, or where the components may move towanls the top of the container due 10 their density, eg. where fit components oat towarls the surface of the plasma In one embodiment, the predefined pattern may indicate that a fibrin polymerisation phase is started, The fibrin polymerisation phase may be scen as the phase where the ‘composition of a blood product is beginning to become ready. The fibrin polymerisation allows the Nbria to be ‘compacted ina subsequent phase, so that the remaining ‘components, thrombocytes and leukocytes, may be adhered to the fibrin, The fibrin polymerisation phase accurs in the blood samples when the coagulation process is started, and ‘occurs when the inital blood separation has been stated In one embodiment, the predefined pattern indicates that the amplitude ofthe sign iss reached a substantially steady sate over time, In some eases of blood separation ia focordance with the invention, physical properties of the blood sample may'be in such a way thatthe amount of fibrin in the liquid of plasma may not he enotigh for the blood sample 1 start the phase of fibrin compression. Such a case ‘may’ occur when a patient is on medication to redice blood ‘lotting, when the patient has liver diseases that reduce the production of fibrinogen, should the patient have bereditary abnormalities to fibrinogen or other pysieal frtors whieh the patient may have. Thus, when the fibrinogen has com pleted its polymerisition, the amplitude ofthe opteal signal tay be tichanged over time, which indicates that the process is completed and thatthe fibrin compression stage ‘will ot commence. Ths itis possible to alt the conti ation at this poiat in time In one embodiment, the predefined pattera indicates that atleast the fibrin compression phase ofthe blood sample is Sarid. For the production ofa ibrin based blood product it may be advantageous that the fibrin compression phase of the blood centrfngation i started during centrifigation. The fibrin compression phase ensures thatthe specific compo- rents of the whole bla, such as leukocytes (white blood prises o fop end for receiving the blood sample con- tainer and a bottom end for holding the blood sample container where the receptacle is at an angle 10 the rotational axis ofthe centitvge, where the centefgal force extends from the top end of the receptacle towards the bottom end of the receptacle, conioller means for controlling the rotational speed of the at least one optical transmitter for transmitting an optical signal through a wal ofthe blood sample container to Aan opposite wall of the blood sample container in & direction that is at an angle of about 30 depres wp to about 90 degrees relative to the gravitational axis of the receptacle and through an upper portion of the blood sample container, at least one optical receiver Joeated on aside of the receptacle opposite to the optical transmitter for regis- tering an amplitude ofthe optical signal, whereby an 0 o 20 ‘optical signal path of the optical signal passes from the ‘optical transmitter through no more than one blood sample container and then to the atleast one optical where the optical receiver detects the amplitude of the ‘optical signal, where the amplitude ofthe optical signal reflects @ translucency of an upper phase andor a plasma of a blood sample in the blood sample con- tainer, whereby the amplitude ofthe optical signal over time indicates the blood product formation in the blood sample container, ‘where the controller means is configured to discontinue the rotational movement of the rolor when the ampli- tude of the optical signal over time has fulfilled 3 predefined pattern, indicating that at Teast a brin polymerisation phase of the blood plasma is started. 10. \ centrifuge in acconlance with claim 9, where the contrite comprises at least wo optical teansmitters and {0 optical receivers. 11. A centrifuge in accordance with claim 10 where the ‘wo optical transmitters are adapted to transmit an optical signal into two different upper portions of the receptacle andor the blood sample continee 12. A centrifuge in aecordance with elim 10, where the ‘wo optical ansmitter are adapted to transmit an optical signal angular toa central longittidinal axis ofthe receptacle andor the blood sample container, where a first optical ‘signal i adapted to pass throwgh a first upper portion ofthe receptacle andior the blood sample container and the second ‘optical signal is adapted to pase through an upper portion {hats distal to the frst upper portion ofthe reeeptaele and/or the blood sample container. 13, A centrifuge in accordance with claim 12, where the receptacle comprises a through-going opening allowing the ‘optical signal to pass through the receptacle in a radial tirction ofthe reveptacle 14. A centrifuge in accordance with claim 11, where the ‘so optical transmitters are adapted to transmit an optical jgnal angular toa central longitudinal axis ofthe receptacle andlor the blood sample container, where a first optical signal is adapted to passthrough a fist upper portion ofthe receplacle and/or the blood sample container and the second ‘optical signal is adapted to pass through an upper portion ‘hati distal to the first upper portion ofthe reeeptacle and/or the blood sample container. 18. A centrifuge in accordance with claim 14, where the receptacle comprises through-going opening allowing the ‘optical signal to pass through the receptacle in a radial direction ofthe receptacle 16, A method of centrifuging blood sample in accor dance with claim 2, wherein the predefined pattern com- prises a frst increase in the amplitude ofthe optical signal 17. A method of centrifuging a blood sample in accor dance with cli 16, wherein the predefined pattem further comprises a second increase in amplitude of the optical signal 18. A method of centrifuging a blood sample in accor dance with claim 17, wherein second increase ia amplitude js followed by a decrease in amplitude ofthe optical signal 19. A method of centrifuging a blood sample in accor dance with claim 18, wherein the predefined pattem further ‘comprises a third increase in amplitude ofthe optical signal

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