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`A1
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`FR
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`WORLD ORGANIZATION FOR INTELLECTUAL PROPERTY
`PCT
`
`International Bureau
`INTERNATIONAL APPLICATION PUBLISHED IN ACCORDANCE WITH THE PATENT COOPERATION TREATY (PCT)
`(11) International publication number: WO 00/22418
`(51) International patent classification7:
`
`
`G01N 21/25
`(43) International publication date: 20 April 2000 (04/20/00)
`
`
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`(21) International file number:
`(81) Designated states: AE, AL, AM, AT, AU, AZ, BA, BB,
`
`BG, BR, BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM,
`(22) International application date:
`EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN,
`
`4 October 1999 (10/04/99)
`IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU,
`
`LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT,
`(30) Priority information:
`RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ,
`
`98/12757
`8 October 1998 (10/08/98)
`UA, UG, US, UZ, VN, YU, ZA, ZW, ARIPO patent
`
`(GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW);
`(71) Applicant (for all designated countries except US):
`Eurasian patent (AM, AZ, BY, KG, KZ, MD, RU, TJ,
`MAXMAT SA [FR/FR]; Cap Alpha, avenue de
`TM); European patent (AT, BE, CH, DE, DK, EE, ES,
`l'Europe, Clapiers, F-34940 Montpellier Cedex 9 (FR).
`FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OAPI
`patent (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML,
`MR, NE, SN, TD, TG).
`
`PCT/FR99/02360
`
`
`
`Published
`
`With international search report.
`
`
`
`
`(72) Inventor(s); and
`(75) Inventor(s)/applicant(s) (only for US):
`RANDRIANARIVO, Jeanet [FR/FR]; 6, rue de Chêne,
`F-34380 Saint Martin de Londres (FR). VERMEULEN,
`Christiaan [BE/FR]; route de grand Champs, Le Noiret,
`F-74350 Cruseilles (FR). CHOJNACKI, André [FR/FR];
`1, chemin de Charlaix, F-38240 Meylan (FR).
`
`
`(74) Attorney: HECKE, Gérard; Cabinet Hecke, WTC
`Europole, 5, place Robert Schuman, P.O. Box 1537, F-
`38025 Grenoble Cedex 1 (FR).
`
`
`
`
`
`(54) Title: OPTICAL MEASURING HEAD, IN PARTICULAR FOR AUTOMATIC CHEMICAL OR BIOLOGICAL
`REACTION ANALYZER
`
`
`(57) Abstract
`
`
`The invention concerns an optical measuring
`head (10) for an automatic laboratory chemical or
`biochemical reaction comprises a first colorimetric
`analysis detector (12) that is controlled by a light
`source (20) associated with an optical fiber (28)
`for transmission of the light beam to one of the
`sides of the reaction analysis plate (18). A
`photodetector device (37) is arranged on the
`opposite side in order to collect the light beam
`emerging from the well (16). The light source (20)
`and the reaction analysis plate (18) are fixed,
`whereas the measuring head (10) is mounted on a
`U-shaped mobile support (19) that frames the
`parallel opposite sides of the analysis plate (18)
`and can be displaced by means of a drive
`mechanism (48) so as to face a predetermined well
`(16). The optical fiber (28) has one end secured to
`the fixed light source (20) and an opposite end
`arranged in a housing (30) of the mobile support
`(19).
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`FOR INFORMATION ONLY
`
`Codes for the identification of PCT designated states in the headers of documents in which international applications are
`published in accordance with PCT.
`
`AL Albania
`AM Armenia
`AT Austria
`AU Australia
`AZ Azerbaijan
`BA
`Bosnia and Herzegovina
`BB
`Barbados
`BE
`Belgium
`BF
`Burkina Faso
`BG
`Bulgaria
`BJ
`Benin
`BR
`Brazil
`BY
`Belarus
`CA
`Canada
`CF
`Central African Republic
`CG
`Congo
`CH
`Switzerland
`CI
`Côte d’Ivoire
`CM Cameroon
`CN
`China
`CU
`Cuba
`CZ
`Czech Republic
`DE Germany
`DK Denmark
`EE
`Estonia
`
`Lesotho
`LS
`Lithuania
`LT
`Luxembourg
`LU
`Latvia
`LV
`MC Monaco
`MD Republic of Moldova
`MG Madagascar
`MK The former Yugoslav
`Republic of Macedonia
`ML Mali
`MN Mongolia
`MR Mauritania
`MW Malawi
`MX Mexico
`NE Niger
`NL Netherlands
`NO Norway
`NZ New Zealand
`PL
`Poland
`PT
`Portugal
`RO
`Romania
`RU
`Russian Federation
`SD
`Sudan
`SE
`Sweden
`SG
`Singapore
`
`Slovenia1
`SI
`Slovakia
`SK
`Senegal
`SN
`Swaziland
`SZ
`Chad
`TD
`Togo
`TG
`Tajikistan
`TJ
`Turkmenistan
`TM
`Turkey
`TR
`Trinidad and Tobago
`TT
`UA Ukraine
`UG Uganda
`US
`United States of America
`UZ Uzbekistan
`VN Viet Nam
`YU Yugoslavia
`ZW Zimbabwe
`
`Spain
`ES
`Finland
`FI
`France
`FR
`GA Gabon
`GB United Kingdom
`GE Georgia
`GH Ghana
`GN Guinea
`GR Greece
`HU Hungary
`IE
`Ireland
`IL
`Israel
`IS
`Iceland
`IT
`Italy
`JP
`Japan
`KE Kenya
`KG Kyrgyzstan
`KP
`Democratic People’s
`Republic of Korea
`Republic of Korea
`KR
`KZ Kazakhstan
`LC
`Saint Lucia
`LI
`Liechtenstein
`LK
`Sri Lanka
`LR
`Liberia
`
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`1
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`PCT/FR99/02360
`
`WO 00/22418
`
`
`
`
`
`Optical measuring head, in particular for automatic chemical or biochemical
`reaction analyzer
`
`
`
`
`Technical Field of the Invention
`
`The invention relates to an optical measuring head, particularly for an automatic
`laboratory chemical or biochemical reaction analyzer designed to determine the dosing
`of components contained in samples after mixing with reagents in wells of a reaction
`analysis plate, said measuring head comprising:
`- a first calorimetric analysis detector controlled by a light source associated with
`an optical fiber for transmission of the light beam to one of the sides of the
`reaction analysis plate, coinciding with the optical axis of a predetermined well,
`which is made of transparent material,
`- means for focusing the light beam when the latter passes through the reaction
`mixture in said well,
`- a photodetector device arranged on the opposite side of the analysis plate to
`collect the light beam emerging from the well after this beam has been subjected
`to an attenuation,
`- and an electronic circuit for processing the signal delivered by the photodetector
`device in order to determine the light spectrum or the optical density of the
`reaction mixture.
`
`
`Prior Art
`
`In order to measure the optical density of a solid, liquid, or gaseous medium, it is
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`necessary to have a reference light source. This light source cooperates with an optical
`focusing, collimating, or filtering system to generate the incident beam passing through
`the medium. The transmitted light intensity is quantified by a photodetector. A
`processing circuit calculates the final value by forming a ratio between the current
`measurement and a measurement of a neutral reference medium, or the ratio between
`the current measurement and a measurement made by means of a second
`photodetector placed on the light source.
`
`In the case of polychromatic or spectrophotometric measurement, the light source is in
`the form of a halogen or xenon lamp that generates a white light. The problem occurs
`when multiple media from different locations are to be analyzed sequentially. Two
`solutions are usually adopted: the static system and the dynamic system.
`
`The static system uses no moving elements, which makes it necessary to increase the
`light sources and the photodetectors at each sample location. It has also been proposed
`to make use of a single light source associated with a multi-strand bundle of optical
`fibers leading to each measurement location. In addition to the cost of such an
`installation, the light energy transmitted to each sample is inversely proportional to the
`number thereof, which entails an increase in amplification gain. The signal-to-noise ratio
`of each measurement is also degraded.
`
`The mobile system adopts a single-channel measurement chain and offers two options:
`
`The whole of the analysis plate carrying the wells can be moved so as to bring each
`sample to the fixed measuring head. During measurements of liquid samples, the light
`beam passes through the medium perpendicular to the transparent flat bottom of the
`well and the meniscus of the sample. Any mechanical vibration of the analysis plate
`causes deformations or surface waves on the meniscus, with the risk of measurement
`errors.
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`PCT/FR99/02360
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`WO 00/22418
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`Documents FR-A-2 669 428 and DE-A-3500639 describe devices in which the samples
`are placed on a rotating disc cooperating with a fixed measuring head.
`
`The entire measurement chain is mobile, and the samples of the analysis plate are
`fixed. Nevertheless, the vibrations of the filament lamps can lead to measurement errors
`and degrade the life of the lamps.
`
`Object of the Invention
`
`-
`
` A
`
` first object of the invention is to achieve an improved optical measuring head for a
`sample analyzer that employs high-precision colorimetry.
`
` A
`
` second object of the invention is to provide a multiple optical measuring head suitable
`for an automatic analyzer comprising at least two measurement systems for different
`applications, enabling the same equipment for storing samples, reagents, sampling, and
`the same analysis plate to be stored.
`
`The optical measuring head according to the invention is characterized in that:
`-
`the light source and the reaction analysis plate are fixed,
`-
`the measuring head is mounted on a U-shaped mobile support that frames the
`parallel opposite sides of the reaction analysis plate and can be displaced by
`means of a drive mechanism in order to cause the first colorimetric analysis
`detector to face a predetermined well, and
`the optical fiber has one end secured to the fixed light source and an opposite
`end arranged in a first housing of the mobile support.
`
`-
`
`
`The light source and the analysis plate are isolated from the measuring head, and the
`advantage of the system lies in the fact that the light source and the sample to be
`analyzed are protected from mechanical vibrations. Only the optical fiber arranged
`between the fixed light source and the bottom part of the mobile support is subjected to
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`PCT/FR99/02360
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`torsional and flectional deformation movements during positioning of the measuring
`head. In order to prevent premature wear of the optical fiber due to the mechanical
`friction caused by deformation, optical fibers that are provided with an external
`protective film made of highly resistant material should advantageously be used.
`
`According to a preferred embodiment, the first housing of the mobile support contains
`an optical collimator for delivering a parallel light beam and an LD1 reference
`photoelectric detector that is connected to the electronic circuit in order to compensate
`for the light flux variations when deformation of the optical fiber occurs. A second
`housing is located opposite the first housing and contains an optical focusing system
`that is optically linked to the photodetector device.
`
`According to one feature of the invention, the optical focusing system of the
`photodetector device is connected to a diffraction network for static wavelength
`selection.
`
`According to a development of the invention, the measuring head is equipped with a
`second photometric analysis detector that is arranged on the mobile support in order to
`perform an opacimetry measurement. The second photometric analysis detector
`comprises at least one light-emitting diode for emission of a monochromatic light and
`operating in conjunction with a receiver photodiode on the opposite side of the mobile
`support.
`
`It is thus possible to integrate two different reading systems into the measuring head of
`an analyzer, enabling analyses to be performed in biochemistry and immunology on the
`one hand and, on the other hand, for hemostatic reactions using the same sample and
`reagent storage equipment, the same sampling equipment, and the same analysis
`plate.
`
`According to another feature of the invention, the bottom face of the analysis plate is
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`confined in an enclosure that is maintained at a preset temperature by means of a
`thermostatic control. The enclosure is advantageously equipped with a deformable
`flexible wall that enables the mobile support to move under the analysis plate.
`
`Brief Description of the Drawings
`
`Other advantages and features will become more clearly apparent from the following
`description of an embodiment of the invention given only as a non-restrictive example
`and represented in the accompanying drawings, in which:
`- Fig. 1 is a schematic view of the analyzer equipped with a mixed colorimetry and
`photometry measuring head according to the invention;
`- Fig. 2 shows a plan view of Fig. 1;
`- Fig. 3 shows a schematic perspective view of the analyzer, and
`- Fig. 4 is a view similar that of Fig. 1 of an alternative embodiment using a
`colorimetry measuring head.
`
`
`Description of a Preferred Embodiment
`
`In Figs. 1 to 3, a measuring head 10 of a laboratory chemical or biochemical reaction
`analyzer comprises a first calorimetric analysis detector 12 and a second photometric
`analysis detector 14 for determining the dosing of components contained in samples
`such as blood, cerebrospinal liquid, or urine, for example. The control mechanism of the
`automatic analyzer takes a predefined quantity of sample, and a predefined quantity of
`reagent, then performs mixing of these quantities in wells 16 of a reaction analysis plate
`18 in the form of a microplate. Measurement of the evolution of the optical density by
`means of the measuring head 10 defines the concentration of the component to be
`dosed directly according to a pre-established methodology.
`
`The first calorimetric analysis detector 12 uses a polychromatic colorimeter to perform
`analyses in biochemistry and immunology. The second photometric analysis detector 14
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`makes use of monochromatic photometers for hemostasis reactions.
`
`The two detectors 12, 14 are mounted on a U-shaped mobile support 19 that vertically
`frames the parallel opposite sides of the reaction analysis plate 18, which plate is fixed.
`
`Description of the First Calorimetric Analysis Detector
`
`The first colorimetric analysis detector 12 is controlled by a light source 20 arranged in
`fixed manner on the frame of the analyzer and comprising a lamp 22 that is associated
`with an optical focusing device formed by a pair of convergent lenses 24. The light
`energy emitted by the lenses 24 is concentrated on one end 26 of an optical fiber 28 for
`transmission of the light beam to the first colorimetric analysis detector 12. The lamp 22
`used can be of the halogen or Xenon type, for example, having a broad wavelength
`spectrum of between 340 nm and 700 nm, inclusive, i.e., ranging from ultraviolet to
`infrared, or it can be of the laser type.
`
`The other end of the optical fiber 28 is fixed in a first housing 30 at the bottom part of
`the mobile support 19 so as to direct the light beam coinciding with the optical axis of a
`predetermined well 16 of the reaction analysis plate 18. The housing 30 contains an
`optical collimator 32 that is designed to deliver a parallel light beam, which beam
`passes through the transparent bottom of the well 16 and the reaction mixture 34 and
`emerges via the meniscus of the mixture 34. A reference detector 36, which is
`instantiated by a photoelectric cell, for example, is also located in the housing 30 and
`operates in case of fluctuation of the light source 20 or attenuation of the light beam
`following deformation of the optical fiber 28.
`
`The top part of the mobile support 19 is separated from the bottom part by the reaction
`analysis plate 18 and is equipped with a photodetector device 37. The latter device
`comprises an optical focusing system 38 situated in a second housing 39 of the mobile
`support 19 for collecting the light incident on a second optical fiber 40 connected to a
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`diffraction network 42 fixed onto the rear part of the mobile support 19. The diffraction
`network 42 enables static wave length selection to be performed and is associated with
`a plurality of photodiodes 44 that are connected to an electronic processing circuit 46
`designed to detect the incident light spectrum of the reaction mixture. The measurement
`of the optical density results from an equation linking the signal coming from the
`reference detector 36 and the output signal of each photodiode 44.
`
`Movement of the mobile support 19 takes place along two axes (arrows F1 and F2, Fig.
`3) on the horizontal plane and is performed by a drive mechanism 48 with a stepper
`motor 50. The measuring head 10 can thus be positioned coaxially on each well 16 of
`the microplate. The optical collimator 32 illuminates the bottom of the well 16, and the
`light beam passes through the medium of the mixture 34, thereby undergoing an
`attenuation. The optical focusing system 38 at the top part of the measuring head 10
`recovers the beam emerging from the well 16 and conducts it to the diffraction network
`42 and the photodiodes 44 in order to quantify this attenuation.
`
`Only the optical fiber 28 fitted between the fixed light source 20 and the bottom part of
`the mobile support 19 is subjected to torsional and flectional deformation movements
`during the positioning of the measuring head 10 and prevents any transmission of
`mechanical vibrations to the light source 20 and the sample to be measured on the fixed
`analysis plate 18.
`
`To prevent premature wear of the optical fiber 28 due to the mechanical friction caused
`by deformation, optical fibers that are provided with an external protective film made of
`highly resistant material should advantageously be used.
`
`The passage of the light beam through the optical fiber 28 generates an attenuation that
`varies according to the curvature followed for a location across from a predetermined
`well. However, this curvature can vary for the same location between two separate
`measurements following a to-and-fro movement of the mobile support 19. To prevent
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`PCT/FR99/02360
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`WO 00/22418
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`any measurement error arising from these variations, the photoelectric cell of the
`reference detector 36 located in the housing 30 quantifies the cumulated variation of the
`attenuation of the optical fiber 28 and any deviation in the intensity of the light source 20
`that may occur. The electronic circuit 46 takes the measurement supplied by the
`reference detector 36 into account and adjusts the measurements delivered by the
`photodiodes 44.
`
` A
`
` biochemical or immunological reaction undergoes a relatively slow optical density
`evolution, and measurement with a frequency of every thirty seconds is sufficient to
`obtain a reliable result. The mobile support 19 can then scan the other wells 16 before
`returning to perform a measurement on the current well.
`
`Description of the Second Photometric Analysis Detector
`
`The second photometric analysis detector 14 is used for a hemostasis reaction in which
`the reaction mixture in the well 14a is constituted by a sample of human plasma and a
`specific reagent triggering a coagulation effect.
`
`Coagulation is accompanied by a variation of the opacity of the mixture in the well 16a,
`and the role of the photometric analysis detector 14 is to determine, by means of a
`specific algorithm, the time required to achieve coagulation of the reaction mixture.
`
`When hemostatic analysis is performed, the variation of the opacity of the mixture varies
`very quickly at the moment coagulation takes place, and the timing precision must be to
`within a tenth of a second. The coagulation reaction is monitored continuously until the
`blood clot forms.
`
`The mobile support 19 of the measuring head 10 is provided at its bottom part with a
`row of six light-emitting diodes 52 for emission of a monochromatic light, with each light-
`emitting diode being associated with a collimator. The light beam emitted by each diode
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`52 passes through the corresponding reaction well 16a following a vertical path. A
`series of six photodiodes 54 is arranged across from the diodes 52 on the upper part of
`the measuring head 10 and intercepts the beam emerging from each well 16a for an
`opacity measurement. The optical axis of each light-emitting diode 52 corresponds to
`that of a photodiode 54 and to the main axis of the well 16a. The energy supplied by the
`light-emitting diodes 52 is sufficient to perform chronometric hemostatic analyses.
`
`The six sensors of the second photometric analysis detector 14 enable monitoring of
`several hemostatic reactions to be performed in parallel in the six wells 16a.
`
`The present invention enables two different measurement systems arranged on the
`mobile support 19 to be integrated into the measuring head 10. This arrangement
`enables analyses to be initiated in the fields of biochemistry, immunology, or
`hemostasis with the same sample and reagent storage supports, the same sampling
`equipment, and the same reaction wells.
`
` A
`
` reaction in the fields of biochemistry, immunology, and hemostasis must take place
`under conditions that are as close as possible to the natural environment where it
`normally takes place. Moreover, the reagents used are sensitive to any temperature
`variation, especially for the enzyme type. The analysis plate 18 is maintained at
`constant temperature over the entire course of the analysis. More often than not, this
`temperature is fixed at 37 °C in order to coincide with the temperature of the human
`body.
`
`With reference to Fig. 3, the reaction analysis plate 18 is heated to the required
`temperature through forced convection of hot air at a temperature near 37 °C. To limit
`heat losses when the mobile support 19 is moved, a thermal enclosure 56 is arranged
`under the analysis plate 18. The enclosure 56 is made of a flexible material with an
`accordion wall 58 securely affixed to the mobile support 19 and enables the analysis
`plate 18 to be heated to the required temperature with minimum heat loss while allowing
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`full freedom of movement of the mobile support 19 under the analysis plate 18. The
`volume of the enclosure 56 is confined by four side walls and a bottom wall, with the top
`wall being formed by the bottom face of the analysis plate 18. A fan (not shown) makes
`it possible to heat said plate by forced convection, and an electronic circuit controlled by
`temperature sensors ensures thermostatic regulation.
`
`The deformable rear wall fixedly secured to the mobile support 19 is embodied by a
`flexible sheet that is arranged in the form of an accordion 58 and additionally fixed
`against the side walls of the enclosure 56. The movement of the mobile support 19
`deforms the flexible accordion wall 58 while simultaneously ensuring that the
`thermostatic enclosure 56 is kept tightly sealed.
`
`Fig. 4 shows an alternative embodiment of a measuring head 100 that employs a single
`calorimetric analysis detector 112. All parts that are identical to those of the device of
`Fig. 1 will not be described and will bear the same reference numbers in Fig. 4. The
`receiver photodiodes 144 are arranged directly upstream from the optical focusing
`system 138 with respect to the direction of propagation of the light beam. The optical
`fiber 40 is then eliminated.
`
`As will readily be understood, the present invention encompasses other analyses of
`chemical reactions, and the method of measurement by mobile optical fiber 28 of the
`first calorimetric analysis detector 12 can be applied to any characterization of a solid,
`liquid or gas medium in transmission, reflection, refraction, diffraction, or diffusion using
`a natural, polarized, or coherent light in a monochromatic or polychromatic mode.
`
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`11
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`Claims
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`PCT/FR99/02360
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`
`1.
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`An optical measuring head for an automatic laboratory chemical or biochemical
`reaction analyzer designed to determine the dosing of components contained in
`samples after mixing with reagents in wells (16, 16a) of a reaction analysis plate
`(18), said measuring head comprising:
`- a first colorimetric analysis detector (12, 122) that is controlled by a light
`source (20) associated with an optical fiber (28) for transmission of the
`light beam to one of the sides of the reaction analysis plate (18),
`coinciding with the optic axis of a predetermined well, which well is made
`of transparent material,
`- means for focusing the light beam when it passes through the reaction
`mixture (34) in the well (16),
`- a photodetector device (37) that is arranged on the opposite side of the
`analysis plate (18) in order to collect the light beam emerging from the well
`(16) after this beam has been subjected to an attenuation,
`- and an electronic processing circuit (46) for processing the signal
`delivered by the photodetector device (37) in order to determine the light
`spectrum or the optical density of the reaction mixture (34),
`characterized in that:
`-
`the light source (20) and the reaction analysis plate (18) are fixed,
`-
`the measuring head (10, 100) comprises a U-shaped mobile support (19)
`that frames the parallel opposite sides of the reaction analysis plate (18),
`and a drive mechanism (48) of the mobile support for causing the first
`calorimetric analysis detector (12, 112) to face a predetermined well,
`the optical fiber (28) has one end secured to the fixed light source (20)
`and an opposite end arranged in a first housing (30) of the mobile support
`(19).
`
`-
`
`
`2.
`
`30
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`The optical measuring head according to claim 1, characterized in that the first
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`housing (30) of the mobile support contains an optical collimator (32) for
`delivering a parallel light beam and a reference photoelectric detector (36) that is
`connected to the electronic circuit (46) in order to compensate for the light flux
`variations when deformation of the optical fiber (28) occurs.
`
`5
`
`
`3.
`
`
`4.
`
`
`5.
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`6.
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`7.
`
`
`8.
`
`10
`
`15
`
`20
`
`25
`
`30
`
`The optical measuring head according to claim 2, characterized in that the mobile
`support (19) comprises a second housing (39) located opposite the first housing
`(30) and contains an optical focusing system (38) that is optically linked to the
`photodetector device (37).
`
`The optical measuring head according to claim 1, characterized in that the optical
`focusing system (38) is connected to a diffraction network (42) for a static
`wavelength selection.
`
`The optical measuring head according to claim 4, characterized in that the optical
`focusing system (38) is connected to a diffraction network (42) by means of a
`second optical fiber (40).
`
`The optical measuring head according to any one of claims 1 to 5, characterized
`in that the measuring head (10) is equipped with a second photometric analysis
`detector (14) that is arranged on the mobile support (19) in order to perform an
`opacimetry measurement.
`
`The optical measuring head according to claim 6, characterized in that the
`second photometric analysis detector (14) comprises at least one light-emitting
`diode (52) for emission of a monochromatic light and operating in conjunction
`with a receiver photodiode (54) on the opposite side of the mobile support (19).
`
`The optical measuring head according to any one of claims 1 to 7, characterized
`in that the bottom face of the analysis plate (18) is confined in an enclosure (56)
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`that is maintained at a preset temperature by means of a thermostatic control.
`
`
`9.
`
`5
`
`The optical measuring head according to claim 8, characterized in that the
`enclosure (56) is equipped with a deformable flexible wall (58) that enables the
`mobile support (19) to move under the analysis plate (18).
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`r,
`
`
`«II MorningSid€ EP
`
`The Leader in Global IP Solutions
`
`TRANSLATOR CERTIFICATION
`
`Date: October 24, 2018
`
`To whom it may concern:
`
`I, Christian Paul Scrogum, a translator fluent in the French and English languages, on
`behalf of Morningside Translations, do solemnly and sincerely declare that the following
`is, to the best of my knowledge and belief, a true and correct translation ofthe
`
`document(s) listed below in a form that best reflects the intention and meaning of the
`
`original text.
`
`I understand that willful false statements and like are punishable by fine or
`imprisonment, or both (18 U.S.C. 1001), and all statements made of my own knowledge
`are true and all statements made on information and belief are believed to be true.
`
`The documents are designated as:
`
`International Application Number: PCT/FR99/02360
`
` Signature
`we (Male/W)
`
`Print
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`Agilent Exhibit 1216
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`Agilent Exhibit 1216
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