WO2002040708A2 - Method for the retention of information data for the application of a biochip/sample support - Google Patents

Method for the retention of information data for the application of a biochip/sample support Download PDF

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Publication number
WO2002040708A2
WO2002040708A2 PCT/DE2001/004290 DE0104290W WO0240708A2 WO 2002040708 A2 WO2002040708 A2 WO 2002040708A2 DE 0104290 W DE0104290 W DE 0104290W WO 0240708 A2 WO0240708 A2 WO 0240708A2
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WO
WIPO (PCT)
Prior art keywords
biochip
data
sample carrier
measuring device
database
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PCT/DE2001/004290
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German (de)
French (fr)
Other versions
WO2002040708A3 (en
Inventor
Peter Boll
Franz Drobner
Christian Kassel
Original Assignee
Siemens Aktiengesellschaft
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Publication of WO2002040708A2 publication Critical patent/WO2002040708A2/en
Publication of WO2002040708A3 publication Critical patent/WO2002040708A3/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/54Labware with identification means
    • B01L3/545Labware with identification means for laboratory containers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584Control arrangements for automatic analysers
    • G01N35/00722Communications; Identification
    • G01N35/00871Communications between instruments or with remote terminals
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/00527Sheets
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/0054Means for coding or tagging the apparatus or the reagents
    • B01J2219/00565Electromagnetic means
    • B01J2219/00569EEPROM memory devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00585Parallel processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00596Solid-phase processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00659Two-dimensional arrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/02Identification, exchange or storage of information
    • B01L2300/021Identification, e.g. bar codes
    • B01L2300/022Transponder chips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/02Identification, exchange or storage of information
    • B01L2300/024Storing results with means integrated into the container
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0636Integrated biosensor, microarrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0663Whole sensors
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL TECHNOLOGY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B70/00Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Abstract

The invention relates to a method for the retention of information data for the application of a biochip/sample support (1), whereby in order to carry out measurements on the biochip/sample support, the useful signals generated are recorded by a sensor device. The biochip/sample support (1), comprising a data store (3), is connected to an external data bank (5), by means of a communication connection (32) in order to transmit the information data for the data bank (5) to the data store (3) or from the data store (3) to the data bank (5).

Description

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_- rt PJ Φ P P P- l-1 P Hi _<; •ö rt J P. φ Φ H cn PJ ι-i P P o tr d P- P- rt J cn_- rt PJ Φ PP P- l- 1 P Hi _ <; • ö rt J P. φ Φ H cn PJ ι-i PP o tr d P- P- rt J cn
P- Φ H cn tr rt o P- • P- φ cn Φ P-1 φ P i tr O P rt PJ= P- Φ Ω φ σ P- o cn P Φ rt O PP- Φ H cn tr rt o P- • P- φ cn Φ P- 1 φ P i tr OP rt PJ = P- Φ Ω φ σ P- o cn P Φ rt OP
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CΛ CΛ P Φ P- CΛ tr P H PJ ja Φ rt PJ tr l-i Q S •d J φ CΛ P P rt φ tr rt O P Pl d N Φ P O P O <! l-J Cd cn s: Φ Φ CΛ P P s: iQ P- lΩ PJCΛ CΛ P Φ P- CΛ tr P H PJ ja Φ rt PJ tr l-i Q S • d J φ CΛ P P rt φ tr rt O P Pl d N Φ P O P O <! l-J Cd cn s: Φ Φ CΛ P P s: iQ P- lΩ PJ
Φ P- 3 E PJ P \ • P- P Q tr w tr O Φ iQ cn P- tr ιQ &5 ^^ • Φ ω P cn Φ P ΦΦ P- 3 E PJ P \ • P- P Q tr w tr O Φ iQ cn P- tr ιQ & 5 ^^ • Φ ω P cn Φ P Φ
P- \ cn tr tr Hi a ω CΛ φ Φ ι-J Φ N Φ P. H φ Φ d πd rt P- s: Q ti cn P P-P- \ cn tr tr Hi a ω CΛ φ Φ ι-J Φ N Φ P. H φ Φ d πd rt P- s: Q ti cn P P-
P PJ J iQ O H • rt ω P P H P- rt P PJ iQ φ i-i P l-J H cn Φ φ d p. PP PJ J iQ O H • rt ω P P H P- rt P PJ iQ φ i-i P l-J H cn Φ φ d p. P
N P H Φ l-i o Φ rt P P Φ • tr Φ P- P P o O Φ P- φ P- Φ 3 <1 ι-i ΩN P H Φ l-i o Φ rt P P Φ • tr Φ P- P P o O Φ P- φ P- Φ 3 <1 ι-i Ω
P P) P- H 3 tr P- P- Φ Φ H Hi iQ P- P1 tr φ rt Φ P Öd iQ tr H Φ cn P J. o P tr <! cn (- φ Hi P J Φ P PJ P- P PJ= O Φ P Φ P- P- rt Φ 1-1 Φ cn tr Φ &> f-i Ω φPP ) P- H 3 tr P- P- Φ Φ H Hi iQ P- P 1 tr φ rt Φ P Öd iQ tr H Φ cn P J. o P tr <! cn (- φ Hi PJ Φ P PJ P- P PJ = O Φ P Φ P- P- rt Φ 1-1 Φ cn tr Φ &> fi Ω φ
Ω CΛ p: Hi rt P tr P rt ^Q l-J tr P P P- Hi P Φ N PJ P rt Φ φ PJ φ P-1 tr Φ H tr Hi l-i Φ P- rt Φ Φ Hi cn Φ 3 N J ιQ P P- Φ ι-i P» ä rt P- rt P= P P- Φ P- Hl t-i M p: P O H P- t-J -> td H PJ P H, P- N 3 KQ tr 3 1-1 Φ P H tr CΛ tö φ cn P JΩ CΛ p: Hi rt P tr P rt ^ Q lJ tr PP P- Hi P Φ N PJ P rt Φ φ PJ φ P- 1 tr Φ H tr Hi li Φ P- rt Φ Φ Hi cn Φ 3 NJ ιQ P P- Φ ι-i P »ä rt P- rt P = P P- Φ P- Hl ti M p: POH P- tJ -> td H PJ PH, P- N 3 KQ tr 3 1-1 Φ PH tr CΛ tö φ cn PJ
Φ P H P : P P H cn rt i-i rt ? cn P P- Φ P" φ pj: t-i Φ P- uq Φ trΦ P H P: P P H cn rt i-i rt? cn P P- Φ P "φ pj: t-i Φ P- uq Φ tr
P- Hi P Ξ cn ιQ Φ < cn φ P- PJ rt P- Φ tu _-" P ιQ 3 > Hl t-i Φ o Φ Ω P t-i σ o rt Φ P φ t-J o cn Ω tr O < J P • φ ι-i φ PJ P Φ O: ι-i Hi P- Ω P ΦP- Hi P Ξ cn ιQ Φ <cn φ P- PJ rt P- Φ tu _- "P ιQ 3> Hl ti Φ o Φ Ω P ti σ o rt Φ P φ tJ o cn Ω tr O <JP • φ ι-i φ PJ P Φ O: ι-i Hi P- Ω P Φ
Φ H P- Φ H PJ l-J l-i P tr Φ P Φ P P cn £ P iQ P f-S KQ tr Φ H P tr & KQ öd PΦ H P- Φ H PJ l-J l-i P tr Φ P Φ P P cn £ P iQ P f-S KQ tr Φ H P tr & KQ öd P
P 3 Φ l-f P rt rt P φ ι-i cn f-i Ω σ φ P P Φ ι-i CΛ Φ P P φ P- φ φ P-P 3 Φ l-f P rt rt P φ ι-i cn f-i Ω σ φ P P Φ ι-i CΛ Φ P P φ P- φ φ P-
• PJ CΛ cn Φ φ 3 H Φ ιQ P P P Hi tr Φ P 3 Q rt P <! Ω P- P- rt t-i *d P P-1 o 3 rt Φ P P P P- N P- P P PJ p: P- H N O tr < Ω rt P Φ ^^ O: Ω P- u P- Ω "*• ** rt rt α. rt rt Q 3 P Ω LSI p: φ s: P Φ tr Φ P- H Φ nd Cd cn r rt p- O tr *d tr Φ P- Φ Φ P O: tr P tr ι-i Φ l-i Φ P φ P P ι-i P> rt P-• PJ CΛ cn Φ φ 3 H Φ ιQ PPP Hi tr Φ P 3 Q rt P <! Ω P- P- rt ti * d P P- 1 o 3 rt Φ PPP P- N P- PP PJ p: P- HNO tr <Ω rt P Φ ^^ O: Ω P- u P- Ω " * • * * rt rt α. rt rt Q 3 P Ω LSI p: φ s: P Φ tr Φ P- H Φ nd Cd cn r rt p- O tr * d tr Φ P- Φ Φ PO: tr P tr ι- i Φ li Φ P φ PP ι-i P> rt P-
Φ P P P N Hi H PJ H 3 H P P KQ φ cn φ ι-i PJ PJ P cn Φ rt o Hl • td P. cn cn rt P P P- p: J Hi N ιQ h-1 P- P PJ -i α P Φ cn P ** 3 Φ rt Φ tr P- ~^ Φ φ P Φ <Q Φ l-J rt TI S P P- P- P PJ s tr Φ Φ l-i P- • f-i Φ P d PΦ PPPN Hi H PJ H 3 HPP KQ φ cn φ ι-i PJ PJ P cn Φ rt o Hl • td P. cn cn rt PP P- p: J Hi N ιQ h- 1 P- P PJ -i α P Φ cn P * * 3 Φ rt Φ tr P- ~ ^ Φ φ P Φ <Q Φ lJ rt TI SP P- P- P PJ s tr Φ Φ li P- • fi Φ P d P
PJ H Φ tr P- Φ H φ P N Ω Hi cn 3 PJ cn P S PJ ö rt P P fi cn rt cn P Φ N t CΛ H O Ö> J P tr J φ P o Φ CΛ PJ P Φ Φ rt P O S rt Φ P CΛ • Φ s: tr ιQ P P •** Ω dd P Ό tö ϊ*r PJ tP CΛ rt P- Hl p- P ι-i P tr φPJ H Φ tr P- Φ H φ PN Ω Hi cn 3 PJ cn PS PJ ö rt PP fi cn rt cn P Φ N t CΛ HO Ö> JP tr J φ P o Φ CΛ PJ P Φ Φ rt POS rt Φ P CΛ • Φ s: tr ιQ PP • * * Ω dd P Ό tö ϊ * r PJ tP CΛ rt P- Hl p- P ι-i P tr φ
Φ P Ω PJ Ω tu Cn o Φ Φ Φ Φ Φ cn tr φ tr rt P- PJ rt iQ Φ Φ Φ O P P): iQ Φ f-i tr tr P tr • rt P- P ι-i P P rt t Φ ι-i PJ O P φ Φ P P 3 ι-i KQ σ Q P E__ φ P- P Hi H P- Φ CΛ PJ= ^ Φ P- ι-i φ P Φ 1 P P l-i 3 Φ J Φ tr rt 3Φ P Ω PJ Ω tu Cn o Φ Φ Φ Φ Φ cn tr φ tr rt P- PJ rt iQ Φ Φ Φ OPP ) : iQ Φ fi tr tr P tr • rt P- P ι-i PP rt t Φ ι- i PJ OP φ Φ PP 3 ι-i KQ σ QP E__ φ P- P Hi H P- Φ CΛ PJ = ^ Φ P- ι-i φ P Φ 1 PP li 3 Φ J Φ tr rt 3
P P P Φ p: 3 H Φ P- rt σ _- o P- Q H • σ PJ= o P. öd PJ P" rt ι-( Φ t-i PJ iQ P- tr 3 3 PJ H 1 S rt cn PJ rt P P- P- rt Φ φ cn P>: P--PPP Φ p: 3 H Φ P- rt σ _- o P- QH • σ PJ = o P. öd PJ P "rt ι- (Φ ti PJ iQ P- tr 3 3 PJ H 1 S rt cn PJ rt P P- P- rt Φ φ cn P>: P--
P P Φ o tr φ rt Φ 3 PJ P- rt Φ cn rt ö P φ φ 0 P- CΛ P Φ rt ιQ ΦP P Φ o tr φ rt Φ 3 PJ P- rt Φ cn rt ö P φ φ 0 P- CΛ P Φ rt ιQ Φ
PJ Φ P H Φ H Φ P- O: S P φ φ P H rt φ P w Φ ti 1 o Φ tr P- Φ Φ PPJ Φ P H Φ H Φ P- O: S P φ φ P H rt φ P w Φ ti 1 o Φ tr P- Φ Φ P
P P PJ P P iQ Φ cn P Φ Φ 1 P i-i ι-i P P P J P tr f-iPPP J PP iQ Φ cn P Φ Φ 1 P ii ι-i PPPJP tr fi
P Φ P- • H φ 1 & KQ P 1 P Ω PJ Φ Ω PJ Hi P. PJ cn P Φ rt α α f-j φ P P 3 iQ φ J P tr P1 ι-1 tr e o P- cn P- ^ P 3 Φ J 1 1 1 Φ 1 P α 1 φ h i-i φ PJ P- cn 1 1 1 P P 1 1 rt P Φ P- • H φ 1 & KQ P 1 P Ω P J Φ Ω PJ Hi P. PJ cn P Φ rt α α fj φ PP 3 iQ φ JP tr P 1 ι-1 tr eo P- cn P- ^ P 3 Φ J 1 1 1 Φ 1 P α 1 φ h ii φ PJ P- cn 1 1 1 PP 1 1 rt
für die Ausführung der Messungen im Meßgerät zur Verfügung, um beispielsweise den Proben des Biochips/Probenträgers eine bestimmte vorbehandelte Blutprobe zuzuführen, Antikörper ein- zuspülen etc.for carrying out the measurements in the measuring device, for example to supply the biochip / specimen sample with a specific pretreated blood sample, to flush in antibodies, etc.
Entsprechend einer auf dem Bipochip/Probenträger vorhandenen Identifizierungsnummer, die zur externen Datenbank übertragen wird, kann ein bestimmtes Konto belastet werden. Wird ein bereits verwendeter Biochip/Probenträger nochmals verwendet, kann dann die weitere Benutzung ohne erneute Bezahlung unter¬ bunden werden.A specific account can be debited according to an identification number on the bipochip / sample carrier that is transferred to the external database. If an already used biochip / sample support used again further use without further payment under ¬ can then be prevented.
Auf diese Weise kann die Anwendung von Biochips/Probenträgern in Forschung, insbesondere in der Pharmaforschung, Life- Science, Diagnostik, und Medizintechnik etc. vereinfacht und gezielt, d.h. also datengesichert, nur für autorisierte Personen zugelassen werden.In this way, the use of biochips / sample carriers in research, in particular in pharmaceutical research, life science, diagnostics, and medical technology etc., can be simplified and targeted, i.e. So backed up data are only allowed for authorized persons.
Besonders vorteilhaft ist es, wenn ein die Messungen ausfüh- rendes Meßgerät über eine Kommunikationsverbindung mit der Datenbank verbunden ist, so dass nach dem Anordnen des Biochips/Probenträgers in dem Meßgerät automatisch neben der Kommunikations erbindung zwischen dem Datenträger und dem Meßgerät eine weitere Kommunikationsverbindung zwischen dem Datenträger und der Datenbank hergestellt wird. Dadurch wird ein schnelles, einfaches und automatisiertes Arbeiten mit dem Biochip/Probenträger möglich.It is particularly advantageous if a measuring device carrying out the measurements is connected to the database via a communication link, so that after the biochip / sample carrier has been arranged in the measuring device, in addition to the communication link between the data carrier and the measuring device, a further communication link between the Disk and the database is established. This enables fast, simple and automated work with the biochip / sample holder.
Vorteilhafte Ausgestaltungen der Erfindung gehen aus den Un- teransprüchen hervor.Advantageous embodiments of the invention emerge from the subclaims.
Im folgenden werden die Erfindung und deren Ausgestaltungen im Zusammenhang mit den Figuren näher erläutert. Es zeigen:The invention and its embodiments are explained in more detail below in connection with the figures. Show it:
Figur 1 ein Blockschaltbild zur Erläuterung der Arbeitsweise mit dem erfindungsgemäßen Biochip/Probenträger, und o o M M P1 Figure 1 is a block diagram to explain the operation with the biochip / sample holder according to the invention, and oo MMP 1
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Φ rt J P- Cd φ Φ P P P ti φ PJ P< φ P- ≥! Q Q tr iQ Hi co PJ Φ P P- rt Ω P- P ti Φ cn P PJ P P ≤ cn _- P rt P φ Φ p-Φ rt J P- Cd φ Φ PPP ti φ PJ P <φ P- ≥! QQ tr iQ Hi co P J Φ P P- rt Ω P- P ti Φ cn PP J PP ≤ cn _- P rt P φ Φ p-
P> 1 P rt P fi φ p- o φ P cn KQ Q P. CΛ Φ P. s: PJ Φ Ω cn rt P P ti P rt cn O O » Ω P o rt cnP> 1 P rt P fi φ p- o φ P cn KQ Q P. CΛ Φ P. s: PJ Φ Ω cn rt PP ti P rt cn OO »Ω P o rt cn
"*» Φ Φ s; 3 φ Φ P1 P tr N s: ιQ rt P p: • td 3 P P tr tr tr p- s: P P Φ l-J P cn p- φ P cn Φ cn ti 3 P tr φ PJ J P- Φ P- H PJ: Q Φ Φ ? P- <! φ P- iQ P- P- ti cn PJ= P- P φ Cd P- rt CΛ K P- P- td P tr P" P fi fi tr cn o >q cn S Ω KQ P P- ιQ rt ιQ ι-J Φ Ω P- φ \ Hi Φ rt PJ rt PJ Φ ti cn & rt φ tr P Φ KQ Φ •"*» Φ Φ s; 3 φ Φ P 1 P tr N s: ιQ rt P p: • td 3 PP tr tr tr p- s: PP Φ lJ P cn p- φ P cn Φ cn ti 3 P tr φ PJ J P- Φ P- H PJ: Q Φ Φ? P- <! Φ P- iQ P- P- ti cn PJ = P- P φ Cd P- rt CΛ K P- P- td P tr P "P fi fi tr cn o> q cn S Ω KQ P P- ιQ rt ιQ ι-J Φ Ω P- φ \ Hi Φ rt PJ rt PJ Φ ti cn & rt φ tr P Φ KQ Φ •
P- tr ω s tr α irj o P- t-1 Φ W li t-1 fi rt fi Φ tP rt J P ti H P1 td cn Φ Ω φ Φ CΛ Φ ι-i ti cn PJ φ rt P- CΛ P- rt φ Φ P cn (- PJ tr td H tr D Hl Φ 3 o 3 td P O P- φ Φ P Q cn P- P. φ ? P1 trP- tr ω s tr α irj o P- t- 1 Φ W li t- 1 fi rt fi Φ tP rt JP ti HP 1 td cn Φ Ω φ Φ CΛ Φ ι-i ti cn PJ φ rt P- CΛ P - rt φ Φ P cn (- PJ tr td H tr D Hl Φ 3 o 3 td PO P- φ Φ PQ cn P- P. φ? P 1 tr
•< P- ιQ P- P tr J P- Hi φ §: 3 tr P iQ P ω Cd tQ PJ O: φ• <P- ιQ P- P tr J P- Hi φ §: 3 tr P iQ P ω Cd tQ PJ O: φ
CΛ φ O φ Φ P cn N Φ et φ ti P- PJ Φ Φ P Φ P ti φ P Φ d NCΛ φ O φ Φ P cn N Φ et φ ti P- PJ Φ Φ P Φ P ti φ P Φ d N
P- P-- P- ti O P P P- Φ Hl ii cn P- P <! Φ tQ P- P) Q fi P P- fi φP- P-- P- ti OPP P- Φ Hl ii cn P- P <! Φ tQ P- P ) Q fi P P- fi φ
X? cn P P PJ: Φ fi <l rt o cn P- o P cn Φ 0 P- cn P -1 Φ N φ P O P- J z P φ rt P Φ o ι-J P t P li Φ P M Φ P P cn Φ Φ n φ P Φ tr ΩX? cn PP PJ: Φ fi <l rt o cn P- o P cn Φ 0 P- cn P - 1 Φ N φ PO P- J z P φ rt P Φ o ι-JP t P li Φ PM Φ PP cn Φ Φ n φ P Φ tr Ω
P1 Φ • P- fi PJ. Φ φ φ Φ Φ P φ P- rt P fi Φ trP 1 Φ • P- fi PJ. Φ φ φ Φ Φ P φ P- rt P fi Φ tr
P- P- « J-. P P P- 3 φ P P td Q PJ p Φ KQ P PP- P- «J-. P P P- 3 φ P P td Q PJ p Φ KQ P P
CΛ cn P. o öd l-i Φ CΛ fi P φ Φ 1 < P- ^l P -> 3 P1 φ CΛ ΦCΛ cn P. o öd li Φ CΛ fi P φ Φ 1 <P- ^ l P - > 3 P 1 φ CΛ Φ
Ω Φ Φ 3 ≤ Φ P- φ ti ιQ Φ ≤ 1 ti P φ o P1 PJ cn iQ P O & t rt tr l-J 3 P- P- Ω 1 Φ Φ fi 1 P H Φ rt fi • m P fi 3 tr 1— > 1 P- P- 1 o 1 Φ 1 P 1 P 1 1 1 Ω Φ Φ 3 ≤ Φ P- φ ti ιQ Φ ≤ 1 ti P φ o P 1 PJ cn iQ PO & t rt tr lJ 3 P- P- Ω 1 Φ Φ fi 1 PH Φ rt fi • m P fi 3 tr 1—> 1 P- P- 1 o 1 Φ 1 P 1 P 1 1 1
co co to t P1 P1 co co to t P 1 P 1
C_π o Cπ o π o CπC_π o Cπ o π o Cπ
P. , cn P P <! Cd s: ö φ ö S. P tr 3 H P rt Cd Ω tr Ω φ Cd cn tr ≤ P- f o P- rt Φ Φ φ P- PJ= P- X J Φ P P P P P- O Cd tr h-1 O P- tr 3 P- Ω P- P- & p φ fi ü P- H P ti o tr Φ rt rt ti P P < 3 πd P- cn P. , — , p P- •8 o tr p ti cn P- rt 3 _-" ^ Hl Ω P cn Φ Φ P P P- P P- PJ V td φ o P td Hl Ω Φ Ω Φ rtP., cn PP <! Cd s: ö φ ö S. P tr 3 HP rt Cd Ω tr Ω φ Cd cn tr ≤ P- fo P- rt Φ Φ φ P- PJ = P- XJ Φ PPPP P- O Cd tr h- 1 O P - tr 3 P- Ω P- P- & p φ fi ü P- HP ti o tr Φ rt rt ti PP <3 πd P- cn P., -, p P- • 8 o tr p ti cn P- rt 3 _- "^ Hl Ω P cn Φ Φ PP P- P P- PJ V td φ o P td Hl Ω Φ Ω Φ rt
"*—* 3 P- PJ tr rt φ fi P Φ P Φ t φ P rt S \ td ti P P ^ P- tr P tr P- P iQ rt Ω P tr P- P rt P Φ P ) fi P P- S T) J φ P Td P P- <! P p. H P P"* - * 3 P- PJ tr rt φ fi P Φ P Φ t φ P rt S \ td ti PP ^ P- tr P tr P- P iQ rt Ω P tr P- P rt P Φ P ) fi P P - ST) J φ P Td P P- <! P p. HPP
Φ P φ tr P- ii td H Φ fi 3 rt φ CΛ 1 ti rt PJ fi Q fi fr td Φ Q PJ p: φ KQ cn P φ φ cn tr P PJ: iV P- Φ Ω ω o Φ 3 O P1 ^ ti φ fi ω Φ td P. t i cn P \ Φ Hi H O: g cn O fi P1 tr td tr P PJ N tr P- Td tr P PJ cn . tiΦ P φ tr P- ii td H Φ fi 3 rt φ CΛ 1 ti rt PJ fi Q fi fr td Φ Q PJ p: φ KQ cn P φ φ cn tr P PJ: iV P- Φ Ω ω o Φ 3 OP 1 ^ ti φ fi ω Φ td P. ti cn P \ Φ Hi HO: g cn O fi P 1 tr td tr P PJ N tr P- Td tr P PJ cn. ti
Φ Φ P- N ö P- o P Φ P φ O P cn Φ Φ Φ cn Cd 3 Ξ Φ Ω ti P- P φ PΦ Φ P- N ö P- o P Φ P φ O P cn Φ Φ Φ cn Cd 3 Ξ Φ Ω ti P- P φ P
P- P. P- P p tr ) ω li Hl li P So Cd P- tr P P- P td P- P- p tr O P CO Hi P HlP- P. P- P p tr ) ω li Hl li P So Cd P- tr P P- P td P- P- p tr OP CO Hi P Hl
Ω P rt 3 Φ rt td 3 O φ KQ <! Ω Φ Ω rt Φ o g CΛ rt Φ tr P1 P P. tr fi rt Φ P- PJ ti o P φ PJ φ t cn X tr ti P- Ω φ Ω fi P Φ P ^ tr P) p- φ Ω P) _— . > H P Φ rt 3 • H CΛ fi rt Ω P) Φ PJ. Ω tr ÖD tr PJ. P P P- o Ö* φ fi tr P N fi φ rt p- PJ PJ PJ: cn tr P1 tr P1 ti Q tr P- KQ Φ iQ Cd rt KQ tr P _fc> 3 rt Φ • tr Hi H cn o rt P Cd rt P- P- fi P- Φ φ td Φ P Φ _- ti Φ vQ Φ trΩ P rt 3 Φ rt td 3 O φ KQ <! Ω Φ Ω rt Φ og CΛ rt Φ tr P 1 P P. tr fi rt Φ P- PJ ti o P φ PJ φ t cn X tr ti P- Ω φ Ω fi P Φ P ^ tr P ) p- φ Ω P ) _—. > HP Φ rt 3 • H CΛ fi rt Ω P ) Φ PJ. Ω tr ÖD tr PJ. PP P- o Ö * φ fi tr PN fi φ rt p- PJ PJ PJ: cn tr P 1 tr P 1 ti Q tr P- KQ Φ iQ Cd rt KQ tr P _fc> 3 rt Φ • tr Hi H cn o rt P Cd rt P- P- fi P- Φ φ td Φ P Φ _- ti Φ vQ Φ tr
Φ fi Cd Φ Hi J: s: P P- cn H P Ω P- tr PJ H ti ^^ fi fi φ PJ. P- Φ α O: ΦΦ fi Cd Φ Hi J: s: P P- cn HP Ω P- tr PJ H ti ^ ^ fi fi φ PJ. P- Φ α O: Φ
P & • P- Φ Φ CΛ O P rfs. P P tr Φ H P Td P>: Φ 3 ιQ < cn s: Φ Hi P- cn PJ rt P Φ P- p. P PJ Φ Hl P Φ tr P- Hi ≤ fi rt p- P> φ Φ o td P- cn Hi 3P & • P- Φ Φ CΛ O P rfs. P P tr Φ H P Td P>: Φ 3 ιQ <cn s: Φ Hi P- cn PJ rt P Φ P- p. P PJ Φ Hl P Φ tr P- Hi ≤ fi rt p- P> φ Φ o td P- cn Hi 3
CΛ td P CΛ Φ P li cn PJ cn cn fi P O P P Φ Φ • < φ O P — - P li fi P- φ P rt φ Hl O P Φ cn φ rt P KQ P li vQ P H O P- tr *- φ et N Φ cn ö P CdCΛ td P CΛ Φ P li cn PJ cn cn fi POPP Φ Φ • <φ OP - - P li fi P- φ P rt φ Hl OP Φ cn φ rt P KQ P li vQ PHO P- tr * - φ et N Φ cn ö P Cd
Φ P- Hi Φ PJ g P- 3 S! Cd ti CΛ Φ 3 o h-1 P φ PJ P p-Φ P- Hi Φ PJ g P- 3 S! Cd ti CΛ Φ 3 o h- 1 P φ PJ P p-
P Ω P rt 3 H P1 PH P rt Φ tr \ PJ Φ s: Φ Cd N Φ rt P. -4 K cn P rt iQ PP Ω P rt 3 HP 1 PH P rt Φ tr \ PJ Φ s: Φ Cd N Φ rt P. -4 K cn P rt iQ P
Φ tr φ s: P- P ^* P Φ S> rt o rt co P- Φ li nd P P fi P H φ , — . Ui s: Φ cn fi Φ P P> rt Hl Hl tr P Q α P- t CΛ ti pi: 5ö KQ pj: P fi ti PJ o s: Φ P P. rtΦ tr φ s: P- P ^ * P Φ S> rt o rt co P- Φ lind PP fi PH φ, -. Ui s: Φ cn fi Φ P P> rt Hl Hl tr PQ α P- t CΛ ti pi: 5ö KQ pj: P fi ti PJ os: Φ P P. rt
P. H ti O Φ O Φ Φ cn φ O Φ P. rt Q cn iQ PJ 3 Q. φ P- P- cn Φ φP. H ti O Φ O Φ Φ cn φ O Φ P. rt Q cn iQ PJ 3 Q. φ P- P- cn Φ φ
P σ Φ P ii P- ti rt N H P- fi P 3 Φ S P- φ P KQ Φ P- cn PJ td cn Ω rt PJ Φ 3 P 3 ti P P>: Ω cn P- P- P 1 Φ Φ H Φ cn Φ g H cn Φ cn Φ tP σ Φ P ii P- ti rt NH P- fi P 3 Φ S P- φ P KQ Φ P- cn PJ td cn Ω rt PJ Φ 3 P 3 ti PP>: Ω cn P- P- P 1 Φ Φ H Φ cn Φ g H cn Φ cn Φ t
Φ P- rt 3 PJ PJ Φ rt tr P- P rt cn • Φ Λ P- P- td 3 Φ φ cn P- g ΦΦ P- rt 3 PJ PJ Φ rt tr P- P rt cn • Φ Λ P- P- td 3 Φ φ cn P- g Φ
P P φ rt rt Hi Φ φ PJ rt P- td cn <l P1 P o PJ: &α P Q Ω Φ PPP φ rt rt Hi Φ φ PJ rt P- td cn <l P 1 P o PJ: & α PQ Ω Φ P
P P- Cd P- t? p- Hi H d-- cn 3 rt Φ Ω Φ φ o — P E KQ 3 N Φ PJ tr &>P P- Cd P- t? p- Hi H d-- cn 3 rt Φ Ω Φ φ o - P E KQ 3 N Φ PJ tr &>
< cn φ p- O ii O φ Q O Φ p- P tr P- fi fi P Φ s: 3 P Φ ιq<cn φ p- O ii O φ Q O Φ p- P tr P- fi fi P Φ s: 3 P Φ ιq
Φ Φ td o P φ P P pi: KQ 3 ü P P PJ rt Ω Cd P-1 φ TI fi g P- p>: Ω fi φ Φ fi 3 φ ιQ Ω Φ Ω Φ ^ P Φ P- PJ φ cn tr Td P- Φ ti P- PJ: φ cn εo tr cn fi cn σ p- Φ t P tr P N cn rt rt N H 3 ro a Φ P & IQ rt &> n fu:Φ Φ td o P φ PP pi: KQ 3 ü PP PJ rt Ω Cd P- 1 φ TI fi g P- p>: Ω fi φ Φ fi 3 φ ιQ Ω Φ Ω Φ ^ P Φ P- PJ φ cn tr Td P- Φ ti P- PJ: φ cn εo tr cn fi cn σ p- Φ t P tr PN cn rt rt NH 3 ro a Φ P & IQ rt &> n fu:
P σ Ω iQ p- "* P s: Φ Φ Φ ≤ S P- fi Q iQ ?r rt 00 P KQ r ^i J co rt tdP σ Ω iQ p- "* P s: Φ Φ Φ ≤ S P- fi Q iQ? R rt 00 P K Q r ^ i J co rt td
P ) tr Φ td P N P- P P P P P- Φ φ rt S φ σ Φ H *- φ φ P- P Φ p-P ) tr Φ td PN P- PPPP P- Φ φ rt S φ σ Φ H * - φ φ P- P Φ p-
P. rt Φ P \ P P P φ • P P- cn cn &α 1 P PJ P ) fi P ιQ P- cn o φ Φ i-J T) o ιQ 3 Φ Φ td Ω rt KQ O: P H P 3 o . — . pi: P Φ P ΩP. rt Φ P \ PPP φ • P P- cn cn & α 1 P PJ P ) fi P ιQ P- cn o φ Φ iJ T) o ιQ 3 Φ Φ td Ω rt KQ O: PHP 3 o. -. pi: P Φ P Ω
P P öd fi rt cn φ rt Φ tr Φ Φ pi: P O φ Φ o rt φ ü fi j-> tr cn o Φ O S. cn P- Φ g p- Φ H fi P P P P CΛ öd Φ P. P- Φ P- s: •d N tr Φ • l P P 0: Ω P P PJ: KQ Φ φ P- Ω P- p- φ _t-. P r O 3 tdPP öd fi rt cn φ rt Φ tr Φ Φ pi: PO φ Φ o rt φ ü fi j-> tr cn o Φ O S. cn P- Φ g p- Φ H fi PPPP CΛ öd Φ P. P- Φ P- s: • d N tr Φ • l PP 0: Ω PP PJ: KQ Φ φ P- Ω P- p- φ _t-. P r O 3 thousand
Φ tr PJ Φ P cn ti Q. Q tr Φ rt P- P ti Cd P o P fi — φ ^ P P- cn fi P- Φ tr P P. rt φ PJ CΛ P1 Φ P i P- PJ Ω Φ ti φ o rt rt ^Φ tr PJ Φ P cn ti Q. Q tr Φ rt P- P ti Cd P o P fi - φ ^ P P- cn fi P- Φ tr P P. rt φ PJ CΛ P 1 Φ P i P- PJ Ω Φ ti φ o rt rt ^
P. Ω fi rt p- Φ p- P rt P- H φ J-» Φ N O 3 tr PJ P P- 3 PJ TdP. Ω fi rt p- Φ p- P rt P- H φ J- »Φ N O 3 tr PJ P P- 3 PJ Td
Φ tr P P fi Q 3 cn Q Φ Ω ti σ P • P- 1 P- P- 3 P tr1 P S J Φ fiΦ tr PP fi Q 3 cn Q Φ Ω ti σ P • P- 1 P- P- 3 P tr 1 PSJ Φ fi
P Φ P P . Φ Ω CΛ P tr o PJ p: td P g td P P. P- φ P rt P O ti rt ιQ ua tr tr Φ S ö rt tr CΛ • φ "•^ P. td Ω P et tr t Φ Φ N J tr H φ J ) Φ Φ td cn o Td P P- φ tr Φ P- ιQ cn ΦP Φ PP. Φ Ω CΛ P tr o PJ p: td P g td P P. P- φ P rt PO ti rt ιQ ua tr tr Φ S ö rt tr CΛ • φ "• ^ P. td Ω P et tr t Φ Φ NJ tr H φ J ) Φ Φ td cn o Td P P- φ tr Φ P- ιQ cn Φ
O: o fi Hl fi P s: Φ P P- P rt P fi PJ P- tr Q fi I 0 P- rt Φ d PO: o fi Hl fi P s: Φ P P- P rt P fi PJ P- tr Q fi I 0 P- rt Φ d P
P ιQ p: Hl • rt i PJ rt cn φ tr P P Φ φ o rt 1 P TQ φ J li rtP ιQ p: Hl • rt i PJ rt cn φ tr P P Φ φ o rt 1 P TQ φ J li rt
P 3 Φ fi P1 O Φ Φ rt ** P J Φ P cn fi tr P- φ P - rt PJ Φ ti φ P- fi 1 P P- Φ Φ tr P P- P φ O PJ: Φ «d 3 Φ rt P- P Ω pj:P 3 Φ fi P 1 O Φ Φ rt * * PJ Φ P cn fi tr P- φ P - rt PJ Φ ti φ P- fi 1 P P- Φ Φ tr P P- P φ O PJ: Φ « d 3 P rt P- P Ω pj:
P rt P) Φ φ 3 rt P P. rt PJ P P P- KQP rt P ) Φ φ 3 rt P P. rt PJ PP P-KQ
* P rt P Φ 1 ii O ιQ tr * P rt P Φ 1 ii O ιQ tr
P- fi PJ P. CΛ P- PJ P Φ ιQ P P. rt PJ o P Φ Φ ΦP- fi PJ P. CΛ P- PJ P Φ ιQ P P. rt P J o P Φ Φ Φ
P. Φ P Hi rt Φ P φ P ?v Cπ Φ φ Φ _fc» fi < P- φ o cn P P fiP. Φ P Hi rt Φ P φ P? V Cπ Φ φ Φ _fc »fi <P- φ o cn P P fi
Φ P φ O P- cn Φ P cn « P 3 fi PJ: Φ Ω td <J • ωΦ P φ O P- cn Φ P cn «P 3 fi PJ: Φ Ω td <J • ω
P ti o fi fi <! Ω Cπ < O Φ P fi tr cn rt φ φ tr 1 1 1 Ω 0 tr Φ 3 P- J Φ 1 rt P- fi Cd P Φ tr 3 rt ti 1 P P li 1 1 1 cnP ti o fi fi <! Ω Cπ <O Φ P fi tr cn rt φ φ tr 1 1 1 Ω 0 tr Φ 3 P- J Φ 1 rt P- fi Cd P Φ tr 3 rt ti 1 P P li 1 1 1 cn
1 1 1 1 1 1 1 1
o o to to P1 P1 oo to to P 1 P 1
Cπ o Cπ o Cπ o Cπ tr 3 3 P. fi O: rt Cd O ?v ^q tr KQ g P N P s: < H) ö Cn g P Cd Ω td P < Ω s: tr σCπ o Cπ o Cπ o Cπ tr 3 3 P. fi O: rt Cd O? V ^ q tr KQ g P N P s: <H) ö Cn g P Cd Ω td P <Ω s: tr σ
P P- P P- Φ H Φ cn P O: φ φ Φ Φ P Z Φ Φ φ P- φ td Φ P- cn tr φ P- o tr Φ J P-P P- P P- Φ H Φ cn P O: φ φ Φ Φ P Z Φ Φ φ P- φ td Φ P- cn tr φ P- o tr Φ J P-
P rt P Φ fi rt P cn P PJ fi fi cn P P- cn fi fi P ti Φ cn φ P- P- wP rt P Φ fi rt P cn P PJ fi fi cn P P- cn fi fi P ti Φ cn φ P- P- w
P- cn P1 3 H- P- P ΦP- cn P 1 3 H- P- P Φ
W P H P pi: cn cn P tr P P- CΛ cn Z td cn PJ td cn fW P H P pi: cn cn P tr P P- CΛ cn Z td cn PJ td cn f
Φ P ; Φ g P- tr PJ Φ φ tr P rt P φ Ω g Φ P- H Cd Ω P Φ P- \> td rt g \ φ <!Φ P; Φ g P- tr PJ Φ φ tr P rt P φ Ω g Φ P- H Cd Ω P Φ P- \> td rt g \ φ <!
P Φ J Φ Ω Φ P P- P Φ rt Φ P cn tr Φ P P P- p- tr P 3 fi T) P- P- Φ Td Φ Φ fi rt PJ EP r-> P rt P- Φ cn ιq Φ EP P Ω o Φ Q P H Φ O E fi p: fi tiP Φ J Φ Ω Φ P P- P Φ rt Φ P cn tr Φ PP P- p- tr P 3 fi T) P- P- Φ Td Φ Φ fi rt PJ EP r- > P rt P- Φ cn ιq Φ EP P Ω o Φ QPH Φ OE fi p: fi ti
N P- P P PJ P φ rt fi Φ Z P K P) P tr Ω li φ cn O P< P KQ O tr Hl trN P- PP PJ P φ rt fi Φ ZPKP ) P tr Ω li φ cn OP < P KQ O tr Hl tr
P Φ O P. PJ < p. 3 P tr Φ <Q .fe P φ Φ P P Φ - P P- Φ tr cn cn Φ tr φ o P-P Φ O P. PJ <p. 3 P tr Φ <Q .fe P φ Φ P P Φ - P P- Φ tr cn cn Φ tr φ o P-
P Φ rt O Φ P- ιQ Φ rt φ ti P. fi cn KQ P P- co P p- Φ Z fi Φ H P1 P s: rt cn fi Φ 3 P rt P P1 P N P φ P : td P P P φ Φ PJ: P QP Φ rt O Φ P- ιQ Φ rt φ ti P. fi cn KQ P P- co P p- Φ Z fi Φ HP 1 P s: rt cn fi Φ 3 P rt PP 1 PNP φ P: td PPP φ Φ PJ: PQ
Φ Φ P Φ CO Hl Z J P P Φ 3 rt P o g ^^. PJ P rt P- fi rt rt P rt P fi fi Φ P g P P P1 PJ Φ P P Φ Φ φ T) tr fi P. td fi cn tr fi PJ PΦ Φ P Φ CO Hl ZJPP Φ 3 rt P og ^ ^ . PJ P rt P- fi rt rt P rt P fi fi Φ P g PPP 1 PJ Φ PP Φ Φ φ T) tr fi P. td fi cn tr fi PJ P
P. P H KQ φ Φ fi Φ \ P) g cn 3 EP fi K Ω P- P- PJ. φ 'P- pj: cn p: ιqP. PH KQ φ Φ fi Φ \ P ) g cn 3 EP fi K Ω P- P- PJ. φ ' P- pj: cn p: ιq
Φ Φ tr g Φ EP Cd 3 φ P P O cn P Φ tr ιq o φ tr φ o Q P U3 tr cnΦ Φ tr g Φ EP Cd 3 φ P P O cn P Φ tr ιq o φ tr φ o Q P U3 tr cn
P P P- φ PJ ιQ p- P- cn φ • P cn P- EP _C- α φ φ tr cn Ω Φ Z P PJ Φ PI Φ trP P P- φ PJ ιQ p- P- cn φ • P cn P- EP _C- α φ φ tr cn Ω Φ Z P PJ Φ PI Φ tr
• P EP ü φ o r P P φ Φ Φ Q J H fi Φ td P KQ tr li P- P P Ü P fi φ α KQ tr fi Ω Φ ιQ P- . Cd fi P φ Φ rt ιq PJ: P φ J Φ P- fi P cn rt ti J P Φ φ PJ: tr fi φ P cn fi P- Φ φ rt rt P- CΛ P td P> P ιq "• Φ P. cn rt P fi P- rt P- Φ cn ö p: P PJ= P P cn fi Ω P) ^ fi P- rt• P EP ü φ or PP φ Φ Φ QJH fi Φ td P KQ tr li P- PP Ü P fi φ α KQ tr fi Ω Φ ιQ P-. Cd fi P φ Φ rt ιq PJ: P φ J Φ P- fi P cn rt ti JP Φ φ PJ: tr fi φ P cn fi P- Φ φ rt rt P- CΛ P td P> P ιq "• Φ P . cn rt P fi P- rt P- Φ cnö p: P PJ = PP cn fi Ω P ) ^ fi P- rt
Φ ιQ PJ= rt td P- td P P- tr PJ Hl rt KQ rt rt >fc. PJ. tr g P d P- 3 co < N P φ ΦΦ ιQ PJ = rt td P- td P P- tr PJ Hl rt KQ rt rt> fc. PJ. tr g P d P- 3 co <N P φ Φ
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Es ist auch denkbar, den Biochip/Probeträger 1 so einzuset¬ zen, dass zunächst nur ein Teil seiner Proben 2 (z. B. 10000 Proben) zu bestimmten Messungen herangezogen werden. Die da- bei vom Meßgerät 4 gewonnenen Meßergebnisse werden über die Kommunikationsverbindung 32 zur externen Datenbank 5 übertragen und dort in einem Speicher abgelegt. Wenn dann ein anderer Teil der Proben 2 (z. B. 5000 Proben) desselben Biochips/Probeträgers 1 zu einem anderen Zeitpunkt zu Messungen herangezogen werden, werden die vom Meßgerät 4 gewonnenen Meßergebnisse ebenfalls zur externen Datenbank 5 über die Kommunikationsverbindung 32 übertragen und im Speicher der Datenbank 5 abgespeichert, sodass sie zusammen mit den bereits abgespeicherten früheren Meßergebnis zur Verfügung stehen.It is also conceivable, the biochip / sample carrier 1 so einzuset ¬ zen, that initially only a part of its samples 2 (z. B. 10000 samples) are used at certain measurements. The measurement results obtained by the measuring device 4 are transmitted to the external database 5 via the communication link 32 and stored there in a memory. If another part of the samples 2 (e.g. 5000 samples) of the same biochip / sample carrier 1 is then used for measurements at a different time, the measurement results obtained by the measuring device 4 are likewise transmitted to the external database 5 via the communication connection 32 and in the memory stored in the database 5, so that they are available together with the earlier measurement result already stored.
Ebenso ist es denkbar, verschiedene Chip-Daten aus dem Datenspeicher 3 des Biochip/Probeträgers 1 auszulesen und über die Kommunikationsverbindungen 31, 32 zur externen Datenbank 5 zu übertragen, sodass sie von dieser' z. B. über Internet zur Verfügung gestellt werden können. Solche Chip-Daten betreffen beispielsweise Daten zur Steuerung von Messungen im Meßgerät 4, Informationen über die Art der Proben und anzuwendenden Anregungstrahlen etc.It is also conceivable to read out various chip data from the data memory 3 of the biochip / sample carrier 1 and to be transmitted over the communication links 31, 32 to the external database 5 so that it e.g. from this'. B. can be made available on the Internet. Such chip data relate, for example, to data for controlling measurements in the measuring device 4, information about the type of samples and excitation beams to be used, etc.
Ferner ist es möglich, Daten, bei denen es sich beispielsweise um zuvor im Meßgerät 4 aufgenommene Meßdaten handelt, vom Meßgerät 4 über die Kommunikationsverbindung 31 in den Datenträger 3 zurückzuschreiben, so dass sie dann später für weitere Messungen bzw. Auswertungen (z.B. für klinische Studien, Datenschutz, Qualitätssicherung etc.) im Meßgerät 4 -und/oder in der Datenbank 5 und/oder in einem anderen externen Auswertegerät aufgerufen werden können und zur Verfügung stehen. Furthermore, it is possible to write back data, which is, for example, measurement data previously recorded in the measuring device 4, from the measuring device 4 to the data carrier 3 via the communication link 31, so that they can later be used for further measurements or evaluations (for example for clinical studies , Data protection, quality assurance etc.) can be called up in the measuring device 4 and / or in the database 5 and / or in another external evaluation device and are available.

Claims

Patentansprüche claims
1. Verfahren zum Erhalten von Informationsdaten für die Anwendung eines Biochips/Probenträgers, wobei zur Ausfüh- rung von Messungen an dem Biochip/Probenträger (1) erzeugte Nutzsignale von einer Sensoreinrichtung erfaßt werden, dadurch gekennzeichnet, dass der einen Datenspei¬ cher (3) aufweisende Biochip/Probenträger (1) über eine Kommunkationsverbindung (32) mit einer externen Datenbank (5) verbunden wird, um die Informationsdaten aus der Datenbank (5) zum Datenspeicher (3) oder vom Datenspeicher (3) zur Datenbank, (5) zu übertragen.1. A method for obtaining information data for the application of a biochip / sample carrier, wherein the execution tion (1) useful signals generated are detected by a sensor means of measurements on the biochip / sample carrier, characterized in that the one Datenspei ¬ cher (3) having biochip / sample carrier (1) via a communication link (32) with an external database (5) in order to transfer the information data from the database (5) to the data store (3) or from the data store (3) to the database (5) transfer.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass der Biochip/Probenträger (1) in einem die Messungen ausführenden Meßgerät (4) angeordnet wird, das über die Kommunikationsverbindung (32) mit der Datenbank (5) und über eine weitere KommunikationsVerbindung (31) mit dem Biochip/Probenträger (1) verbunden wird, und dass die Infor- mationsdaten dem Datenspeicher (3) und/oder einem Speicher des Meßgerätes (4) zugeführt werden.2. The method according to claim 1, characterized in that the biochip / sample carrier (1) is arranged in a measuring device (4) which carries out the measurements and which is connected to the database (5) via the communication link (32) and via a further communication link (31 ) is connected to the biochip / sample carrier (1), and that the information data are supplied to the data memory (3) and / or a memory of the measuring device (4).
3. Verfahren nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass als Informationsdaten Informationen zum Freischalten des Biσchips/Datenträgers (1) und/oder die Software, die zur Ausführung der Messungen erforderlich ist und/oder Daten zur Abrechnung von Kosten, die die Ausführung der Messungen betreffen übertragen werden.3. The method according to claim 1 or 2, characterized in that as information data information to unlock the Biσchips / data carrier (1) and / or the software that is required to carry out the measurements and / or data for billing costs that the execution of the measurements concerned are transmitted.
4. Verfahren nach Anspruch 3,. dadurch gekennzeichnet, dass die Informationsdaten gegen Bezahlung übertragen werden.4. The method according to claim 3 ,. characterized in that the information data is transmitted against payment.
5. Verfahren nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass der Biochip/Probenträger (1) in einem die Messungen ausführenden Meßgerät (4) angeordnet wird, das über die Kommunikationsverbindung (32) mit der Datenbank (5) und über eine weitere Kommunikationsverbindung (31) mit dem Biochip/Probenträger (1) verbunden wird, und dass die Informationsdaten aus dem Datenspeicher (3) zur externen Datenbank (5) übertragen und in dieser gespei¬ chert werden.5. The method according to any one of claims 1 to 4, characterized in that the biochip / sample carrier (1) is arranged in a measuring device (4) carrying out the measurements, which is connected to the database (5) and via a communication link (32) further communication link Is (31) connected to the biochip / sample carrier (1), and that transmit the information data from the data memory (3) to the external database (5) and in this chert ¬ vomit.
6. Verfahren nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass als Kommunikationsverbindung (32) eine Internetverbindung aufgebaut wird.6. The method according to any one of claims 1 to 5, characterized in that an Internet connection is established as the communication connection (32).
7. Verfahren nach einem der Ansprüche 1 bis 6, dadurch gekennzeichnet, dass von dem Meßgerät (4) erfaßte Meßdaten über die Kommunikationsverbindung (32) zur Datenbank (5) übertragen werden.7. The method according to any one of claims 1 to 6, characterized in that measurement data acquired by the measuring device (4) are transmitted via the communication link (32) to the database (5).
8. Verfahren nach einem der Ansprüche 2 bis 7, dadurch gekennzeichnet, dass Daten in den Datenträger (3) vom Meßgerät (4) über die weitere Kommunikationseinrichtung (31) zurückgeschrieben werden und dann später zur weiteren Auswertung im Meßgerät (4) und/oder in der Datenbank (5) und/oder in einem anderen externen Auswertegerät aufgerufen werden.8. The method according to any one of claims 2 to 7, characterized in that data in the data carrier (3) from the measuring device (4) via the further communication device (31) are written back and then later for further evaluation in the measuring device (4) and / or can be called up in the database (5) and / or in another external evaluation device.
9. Biochip/Probenträger zur Ausführung des Verfahrens nach einem der Ansprüche 1 bis 8, dadurch gekennzeichnet, dass er einen Datenspeicher (3) zum Speichern der Informationsdaten enthält.9. biochip / sample carrier for performing the method according to one of claims 1 to 8, characterized in that it contains a data memory (3) for storing the information data.
10. Biochip/Probenträger nach Anspruch 9, dadurch gekennzeichnet, dass der Datenspeicher (3) ein EPROM- oder EEPROM-Speie er ist.10. Biochip / sample carrier according to claim 9, characterized in that the data memory (3) is an EPROM or EEPROM memory.
11. Biochip/Probenträger nach Anspruch 9 oder 10, dadurch gekennzeichnet, dass er Anschlüsse (34) zur Herstellung der weiteren Kommunikationsverbindung (31) in der Form einer körperlichen Verbindung zwischen dem Datenspeicher (3) und dem Meßgerät (4) aufweist. 11. Biochip / sample carrier according to claim 9 or 10, characterized in that it has connections (34) for establishing the further communication connection (31) in the form of a physical connection between the data memory (3) and the measuring device (4).
12. Biochip/Probenträger nach Anspruch 9 oder 10, dadurch gekennzeichnet, dass er elektrooptische Verbindungselemente (6, 7) zur Herstellung der weiteren Kommunikationsverbindung (31) zwischen dem Datenträger (3) und dem Meßgerät 4) aufweist.12. Biochip / sample carrier according to claim 9 or 10, characterized in that it has electro-optical connecting elements (6, 7) for establishing the further communication connection (31) between the data carrier (3) and the measuring device 4).
13. Biochip/Probenträger nach Anspruch 9 oder 10, dadurch gekennzeichnet, dass er induktive Verbindungselemente (8, 9) zur Herstellung der weiteren Kommunikationsverbindung (31) zwischen dem Datenspeicher (3) und dem Meßgerät (4) aufweist .13. Biochip / sample carrier according to claim 9 or 10, characterized in that it has inductive connecting elements (8, 9) for establishing the further communication connection (31) between the data memory (3) and the measuring device (4).
14. Biochip/Probenträger nach einem der Ansprüche 9 bis 13, dadurch gekennzeichnet, dass er die Form eines für ver- schiedene Messungen geeigneten Rohlings aufweist, dessem Datenspeicher (3) Informationsdaten zuführbar oder entnehmbar sind. 14. Biochip / sample carrier according to one of claims 9 to 13, characterized in that it has the form of a blank suitable for various measurements, the data memory (3) of which information data can be supplied or removed.
PCT/DE2001/004290 2000-11-20 2001-11-15 Method for the retention of information data for the application of a biochip/sample support WO2002040708A2 (en)

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