WO2025238032A1 - Optical sample analysis and apparatus therefor - Google Patents
Optical sample analysis and apparatus thereforInfo
- Publication number
- WO2025238032A1 WO2025238032A1 PCT/EP2025/063120 EP2025063120W WO2025238032A1 WO 2025238032 A1 WO2025238032 A1 WO 2025238032A1 EP 2025063120 W EP2025063120 W EP 2025063120W WO 2025238032 A1 WO2025238032 A1 WO 2025238032A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- light
- array
- sensors
- sample analysis
- analysis apparatus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/251—Colorimeters; Construction thereof
- G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/06—Investigating concentration of particle suspensions
- G01N15/075—Investigating concentration of particle suspensions by optical means
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/255—Details, e.g. use of specially adapted sources, lighting or optical systems
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
- G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
- G01N21/51—Scattering, i.e. diffuse reflection within a body or fluid inside a container, e.g. in an ampoule
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N2015/0042—Investigating dispersion of solids
- G01N2015/0053—Investigating dispersion of solids in liquids, e.g. trouble
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
- G01N21/4738—Diffuse reflection, e.g. also for testing fluids, fibrous materials
- G01N2021/4764—Special kinds of physical applications
- G01N2021/4769—Fluid samples, e.g. slurries, granulates; Compressible powdery of fibrous samples
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/06—Illumination; Optics
- G01N2201/062—LED's
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/06—Illumination; Optics
- G01N2201/062—LED's
- G01N2201/0626—Use of several LED's for spatial resolution
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/06—Illumination; Optics
- G01N2201/063—Illuminating optical parts
- G01N2201/0633—Directed, collimated illumination
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/06—Illumination; Optics
- G01N2201/064—Stray light conditioning
- G01N2201/0642—Light traps; baffles
Definitions
- the present invention relates to an optical sample analysing apparatus, which in particular is suitable for use in nephelometry.
- nephelometry In nephelometry, a light beam is directed through a liquid sample containing suspended particles. The intensity of the scattered light at a specific angle is measured. The amount of scattering of the light by the sample is proportional to the concentration of particles in the sample.
- a laser is used as a light source and the laser beam is directed through a vessel holding a sample.
- An integrating sphere in the art also known as an Ulbricht sphere, is arranged in line, with the laser on the opposite side of the vessel such that a light inlet port of the integrating sphere can capture the light going through the vessel.
- a light exit port is located at an angle of 180° of the light inlet port of the sphere, at which exit port a light trap is arranged. The light trap catches the laser beam that is transmitted at 180° through the sphere.
- a further light exit port is arranged in the sphere at an angle different from 180°, for example at an angle of 90° with respect to the axis between the light inlet port and the exit port provided with the light trap.
- a photodetector e.g. a photodiode
- the photodetector is able to detect light that is reflected and diffused by the interior surface of the sphere.
- the light of the laser beam is partially scattered by particles in the sample.
- the laser beam that enters the sphere does not contribute to the scatter light detection because it is caught by the light trap.
- the amount of light detected by the photodetector is a measure for the scattering of the light, and thus is a measure for the amount of particles dissolved in the fluid, or in other words a measure for the turbidity of the sample.
- Nephelometry is commonly used in various scientific and medical fields. It is for example widely used in clinical laboratories to measure the levels of specific proteins or other substances in bodily fluids.
- An example is a method disclosed in EP 2776840 B1 for determining the propensity of a fluid for calcification, using nephelometry in which the sample is excited by a laser beam. This method can be performed with an optical sample analysing apparatus comprising the arrangement including the laser and Ulbricht sphere as outlined in the above.
- An example of such a nephelometry apparatus is brought on the market by BMG Labtech under the name NEPHELOstar® Plus.
- wells i.e. small vessels in which samples are contained, comprised in a well plate, can be aligned one at a time with the laser and the Ulbricht sphere to detect the amount of light scattered by the sample in that well.
- the invention has for an object to provide an optical sample analysing apparatus which is more versatile and more efficient in use.
- optical sample analysing apparatus comprising:
- a vessel receiving part for receiving a vessel containing a sample to be analysed
- a light source configured and arranged to emit a collimated light beam through a vessel placed in the vessel receiving part
- a scatter light detector configured and arranged to detect light scattered by the sample contained in said vessel
- the apparatus comprises a sensor array of light sensors, wherein the scatter light detector is formed by at least one light sensor comprised in said sensor array of light sensors, offset from the direction of the collimated light beam, and wherein the transmission light detector is formed by a light sensor comprised in said sensor array of light sensors, in line with the direction of the collimated light beam.
- the apparatus thus has a scatter light detector and a transmission light detector, whereby the apparatus can be used for analysing a sample via either scatter light detection, i.e. nephelometry, or transmission light detection.
- the apparatus also allows a combination of scatter light detection and transmission light detection.
- the transmission light detector is arranged 180° opposite the light source and allows detection of the amount of light of the collimated light beam that is transmitted through a vessel containing a sample. The amount of transmitted light may provide information about the state or contents of the sample.
- the scatter light detector is arranged at an angle other than 180° from the collimated light beam and allows detection of the amount of light that is scattered by the sample in the vessel.
- the transmission light detector is formed by a light sensor comprised in a sensor array of light sensors, located 180° opposite the light source, i.e. aligned with the direction of the collimated light beam.
- the scatter light detector is formed by at least one light sensor comprised in the same sensor array of light sensors, located offset, from the direction of the collimated light beam, i.e. not 180° opposite the light source.
- An Ulbricht sphere is omitted in the apparatus according to the invention, which is possible because of the detector lay-out in a sensor array as is proposed by the present invention.
- the signal processing unit is programmed to switch between multiple working modes, the working modes comprising:
- the signal processing unit can select the output signals it uses in a certain working mode.
- the scatter detection mode the output signal of the scatter light detector is selected
- the transmission detection mode the output signal of the transmission light detector is selected
- both mentioned output signals are selected.
- the scatter light detector and the transmission light detector both provide an output signal to the signal processing unit, which can processes both signals, but in the scatter detection mode the output signal of the transmission light detector is ignored by the signal processing unit, whereas in the transmission detection mode the output signal of the scatter light detector is ignored.
- the combined mode none of the output signals of the scatter light detector and the transmission light detector is ignored by the signal processing unit, hence they are both used.
- the scatter light detector comprises eight sensors of a 3*3 sub-array except the central sensor of said 3*3 sub-array, or a selection of said eight sensors, wherein:
- an output signal of the central sensor of the subarray is used as a transmission light detector signal representing light transmission through the vessel and the output signals of the surrounding eight sensors are ignored;
- an output signal of the central sensor of the sub-array is used as a transmission light detector signal representing light transmission through the vessel and the output signals of the surrounding eight sensors, or a selection thereof, are used as a scatter light detector signal representing scatter light by the vessel.
- the scatter light detector comprises a plurality of light sensors.
- the plurality of light sensors comprised in the scatter light detector form a sub-array of the sensor array of light sensors.
- the sub-array may for example be a square array of sensors.
- the sub-array is a 3x3 array of sensors, wherein the scatter light detector comprises the eight sensors of said sub-array except the central sensor of said subarray, the central sensor being positioned 180° opposite the light source.
- the scatter light detector may also be a selection of the mentioned eight sensors, for example the four sensors at the corner of the square sub-array.
- the sensor array comprises multiple sub-arrays.
- Each sub-array may comprise a transmission detection sensor and a set of scatter detection sensors surrounding it.
- the sensor array thus comprises multiple transmission detectors and multiple scatter detectors by means of which multiple vessels can be analysed simultaneously.
- adjacent sub-arrays overlap, i.e. some sensors are comprised in both of the adjacent sub-arrays.
- the sensor array has (N+2) x 3 sensors, which is suitable for detecting light of a row of an N * M array of vessels, wherein N and M are integers.
- the sensor array has 10 x 3 light sensors, which together incorporate eight scatter detectors and eight associated transmission detectors. In such a configuration a sensor in the middle row of the three rows is comprised in the scatter detector associated with one vessel and is comprised in the transmission detector associated with the adjacent vessel in the row of vessels. In this way efficient use is made of the sensors in the sensor array.
- each light sensor in the sensor array comprises at least one photodiode.
- the photodiodes are arranged on a printed circuit board (PCB).
- PCB printed circuit board
- the apparatus comprises a plurality of light sources. With a plurality of light sources a plurality of vessels can be illuminated and thus less movement of the vessels is necessary for analysing them. This improves the efficiency of the apparatus.
- the light source or light sources each comprise a light emitting diode (LED).
- LED is a red light emitting diode.
- the LEDs are arranged on a printed circuit board (PCB).
- PCB printed circuit board
- the light source comprises at least one lens to collimate the light beam incident on the vessel.
- the light source comprises a lens stack to collimate the light beam.
- a lens stack the light of a LED can be collimated to a collimated beam that is directed through the vessel containing a sample to be analysed.
- the lens stack may further comprise one or more light traps.
- the one or more light traps catch the light that is not going through the lens(es) and reduces stray light which facilitates collimating the light beam.
- the receiving part comprises a holder for holding a well plate comprising an array of wells, the wells forming the vessels for holding samples.
- a well plate may have an array of N x M wells, wherein N and M are the same integers as described in the above.
- Such a well plate can be combined with the feature that the light sources of the apparatus comprise a row of LEDs on a printed circuit board (PCB), wherein the number of LEDs is N.
- PCB printed circuit board
- the receiving part may comprise a holder for holding one or more cuvettes, the cuvettes forming the vessels for holding samples.
- the invention furthermore relates to a nephelometry apparatus comprising an optical sample analysis apparatus as described in the above.
- the invention also relates to the use of an optical sample analysis apparatus as described in the above in nephelometry.
- the invention furthermore relates to the use of an optical sample analysis apparatus as described in the above in a method for determining the propensity of a fluid for calcification.
- the invention also relates to a nephelometry method comprising the following method steps: a) An N x M array of vessels each holding a sample comprising a liquid is provided, wherein N and M are integers; b) a row of N collimated light beams is created, said row of light beams being aligned with one of the rows of the array of vessels, such that each vessel in the row is illuminated by one collimated light beam; c) an (N+2) x 3 sensor array of light sensors is provided and arranged such that a middle row of the three rows of the sensor array is aligned with the vessels, wherein the first and last light sensor of said middle row are not positioned directly aligned with a vessel; d) a light intensity signal is generated by the individual sensors in the sensor array which are not directly aligned with a vessel and the corresponding collimated light beam; e) said light intensity signals of the individual sensors are fed as input signals to a signal processing unit; f) the signal processing unit computes the scatter
- the invention also relates to a method for determining the propensity of a fluid for calcification, comprising the nephelometry method as described above.
- Fig.1 shows schematically a cross section of an optical sample analysing apparatus according to the invention
- Fig. 2 shows schematically a bottom elevational view of a PCB with LEDs of the apparatus of Fig. 1 ,
- Fig. 3 shows schematically a top elevational view of a PCB with an array of photodiodes of the apparatus of Fig. 1
- Fig. 4 shows a top elevational view of a well plate to be arranged in the apparatus of Fig. 1 and the schematical sensor array of Fig. 3,
- Fig. 5 shows schematically a top elevational view of the array of photodiodes of Fig. 3 with a row of wells aligned with it
- Fig. 6 illustrates a scatter light detection at a first well of the row of wells of Fig. 5,
- Fig. 7 illustrates a scatter light detection at a second well of the row of wells of Fig. 5,
- Fig. 8 illustrates the overlap between adjacent subarrays of the array of photodiodes of Fig. 5.
- Fig. 1 shows an optical sample apparatus 1.
- the optical sample apparatus 1 generally comprises a light source block 2, a receiving means for a well plate 4 and a sensor unit 6.
- the light source block 2 comprises a housing 20 in which a row of tubular cavities 24 is formed.
- a lens stack 21 is provided in each of the tubular cavities 24 .
- eight lens stacks 21 are provided.
- Each lens stack 21 comprises a stack of light trap chambers 23a, 23b and 23c, respectively, which have a collimating lens 22a, 22b and 22c, respectively, which is arranged at one axial end of the light trap chamber 23a, 23b, 23c.
- a further lens 25 is arranged at a bottom end of the tubular cavity 24 .
- the lens 25 is kept in place by a bottom plate 26 which is attached to the housing 20.
- the bottom plate 26 is provided with openings 27 at the lenses 25 to allow light collimated by the light stacks to exit the housing 20 as collimated light beams.
- the light source block 2 furthermore comprises a LED plate 3 which is arranged at a top end of the housing and attached to the housing by fasteners, in this embodiment the fasteners are screws 50.
- a gasket 51 is arranged between the housing 20 and the LED plate 3, which inhibits light to enter from the exterior through the interface between the LED plate 3 and the housing 20 into the interior of the housing 20, in particular into the tubular cavities 24.
- the LED plate 3 comprises a printed circuit board (PCB) 30 which is provided with a row of light emitting diodes (LEDs) 31 , as is shown in Figs 1 and 2.
- the number of LEDs 31 in the row corresponds to the number of tubular cavities 24 and corresponding lens stacks 21.
- the LEDs 31 are arranged such that each of them is positioned at a respective top end of the tubular cavities 24.
- the LEDs 31 are all the same and are preferably emitting red light.
- the sensor unit 6 comprises a printed circuit board (PCB) 60 with an array 61 of photodiodes 62 arranged on the PCB as is illustrated in Fig. 3.
- the array 61 has three rows, which are illustrated in Fig. 3 by a dashed box drawn around the photodiodes and indicated by reference numerals 63a, 63b and 63c, respectively.
- Each of the rows 63a, 63b, 63c in this example has ten photodiodes 62.
- the middle row 63b is arranged in line with the row of LEDs and the corresponding lens stacks 21.
- the photodiodes 62 are connected with a signal processing unit 9, shown schematically in Fig. 3.
- the signal processing unit 9 may be arranged on the PCB 60 or may be incorporated in another component or device, e.g. comprised in a computer.
- FIG. 1 a state is illustrated in which the well plate 4 is placed in said intermediate space 7 in the machine.
- the receiving space 7 is comprised in a receiving part of the machine, which may comprise holding means for holding the well plate 4 and a moving mechanism for moving the well plate 4 with respect to the light source block 2 and the sensor unit 6.
- FIG. 4 A top elevational view of the well plate 4 and the array 61 of photodiodes 62 (cf. Fig. 3) is shown in Fig. 4.
- the well plate 4 has an array of wells 41.
- the well plate 4 shown here has an array of 8*12 wells 41 .
- the vertically drawn rows of eight wells 41 are aligned parallel with the row of LEDs on the LED plate 3.
- the well plate 4 is movable in the intermediate space 7 with respect to the light source block 2 and the sensor unit 6, according to an arrow 8 indicated in Fig. 4. In this way a row of wells 41 can be moved and aligned with the row of LEDs / lens stacks, and with the row 63b of photodiodes 62.
- the wells 41 are vessels having a diameter of about 5 mm and a height of about 10 mm. In use the wells 41 can each hold a sample to be analysed.
- the wells 41 have a wall that allows transmission of light therethrough and have an open top end through which the sample can be injected in the well 41 .
- the wells 41 are filled with a liquid sample.
- the well plate 4 is moved through the intermediate space 7 such that the rows, i.e. the vertical rows indicated 1-12 in Fig. 4 are consecutively aligned with the row of light sources and the centre row 63b of photodiodes 62.
- Fig. 5 is illustrated schematically how a row of wells 41 is aligned with the centre row 63b of the array of photodiodes.
- the first well 41 of the row is taken which may be the well 41 indicated in Fig. 4 by A1, cf. Fig. 6.
- Light is emitted by the LED 31 through the lens stack 21 and is emitted as a collimated light beam into the well 41-A1.
- the light of the beam entering the sample is detectable by a subarray of photodiodes 62, which subarray is illustrated by a dotted box indicated with reference numeral 64A in Fig. 6.
- the subarray 64A is a square array which includes nine photodiodes 62.
- the central photodiode 62CA of this subarray 64 (see Fig. 6) can detect the light beam that goes straight through the sample in the well 41-A1.
- the sample in the well 41-A1 may cause scattering of the light.
- This scattered light is detectable by the photodiodes 62’ of the subarray 64A which are offset from the direction of the collimated light beam.
- these photodiodes 62’ are shaded and surround the central photodiode 62CA of the subarray 64A.
- the intensity of the scattered light at a specific angle can be measured with the photodiodes 62’.
- the amount of scattering of the light by the sample in the well 41 -A1 is proportional to the concentration of particles in the sample and can be detected by the shaded photodiodes 62’ in Fig. 6.
- the detected light by the photodiodes 62’ is a measure of the amount of particles in the sample, which may provide information about the composition of the sample.
- the photodiodes 62’ of the subarray 64A thus function together as a scatter light detector for the well 41-A1.
- the central photodiode 62CA may be used as a transmission light detector to detect light transmission through the vessel 41-A1.
- the scatter light detector comprises eight sensors of a 3*3 subarray 64A except the central sensor 62CA of said 3*3 sub-array. Instead of all sensors 62’ also a selection of said eight sensors 62’ can be used for the scatter light detection.
- the signal processing unit 9 is preferably programmed to switch between multiple working modes. These working modes may comprise a scatter detection mode in which only an output signal of the scatter light detector is used, and a transmission detection mode in which only an output signal of the transmission light detector is used. Also a combined mode is possible in which the output signals of both the scatter light detector and the transmission light detector are used. In a possible embodiment, in the scatter detection mode, an output signal of the central photodiode of the sub-array 64A is ignored and the output signals of the surrounding eight photodiodes 62’, or a selection thereof, are used as a scatter light detector signal representing scatter light by the well 41-A1.
- an output signal of the central photodiode of the sub-array 64A is used as a transmission light detector signal representing light transmission through the well 41 -A 1 and the output signals of the surrounding eight photodiodes 62’ are ignored.
- an output signal of the central photodiode 62CA of the sub-array 64A is used as a transmission light detector signal representing light transmission through the well 41 -A1 and the output signals of the surrounding eight photodiodes 62’, or a selection thereof, are used as a scatter light detector signal representing scatter light by the well 41-A1.
- the signal processing unit 9 provides measurement values of the scatter light detector and/or the transmission light detector.
- the signal processing unit is programmed to convert these measurement values to metrics about the composition of the sample.
- the signal processing unit may communicate with a computer that determines the metrics about the composition of the sample.
- the sample in the well 41 indicated in Fig. 4 by B1 can be analysed.
- Light is emitted by the LED 31 through the lens stack 21 and is emitted as a collimated light beam into the well 41-B1.
- the light of the beam entering the sample is detectable by a subarray of photodiodes 62, which subarray is illustrated by a dotted box indicated with reference numeral 64B in Fig. 7.
- the subarray 64B is a square array which includes nine photodiodes 62”.
- the central photodiode 62CB of this subarray 64B (see Fig. 7) can detect the light beam that goes straight through the sample in the well 41 -B1 .
- the sample in the well 41-B1 may cause scattering of the light.
- This scattered light is detectable by the photodiodes 62” of the subarray 64B which are offset from the direction of the collimated light beam.
- these photodiodes 62” are shaded and surround the central photodiode 62CB of the subarray 64B.
- the intensity of the scattered light at a specific angle can be measured with the photodiodes 62”.
- the amount of scattering of the light by the sample in the well 41 -B1 is proportional to the concentration of particles in the sample and can be detected by the shaded photodiodes 62” in Fig. 7.
- the detected light by the photodiodes 62” is a measure of the amount of particles in the sample, which may provide information about the composition of the sample.
- the photodiodes 62” of the subarray 64B thus function together as a scatter light detector for the well 41 -B1.
- the central photodiode 62CB may be used as a transmission light detector to detect light transmission through the vessel 41-B1.
- FIG. 8 shows that light passing through the wells 41-A1 and 41-B1 is detected with partially the same photodiodes. This is illustrated in Fig. 8, which show that the subarrays 64A and 64B are overlapping.
- the photodiodes in the overlap i.e. the photodiodes that are comprised in both of the adjacent sub-arrays 64A and 64B, are depicted with a dotted pattern in Fig. 8.
- the LEDs 31 in the row of LEDs are activated consecutively, whereby the subarrays 64A, 64B, ... , 64H, are correspondingly used to detect scatter and/or transmission of light.
- the subarrays 64A, 64B, ... , 64H are correspondingly used to detect scatter and/or transmission of light.
- the well plate 4 can be moved in the direction 8, whereby the next row, i.e. the row of wells A2 to H2 in Fig. 4, is positioned underneath the row of LEDs 31 and associated lens stacks 21, and above the middle row 63b of photodiodes 62, after which the above described process is executed again. This can be repeated until all rows (vertical rows 1-12 in Fig. 4) are measured.
- the above optical sample analysis apparatus 1 can be used in a nephelometry apparatus.
- the optical analysis apparatus can be adapted and configured to perform a nephelometry method comprising the following method steps: a) An N * M array of vessels each holding a sample comprising a liquid is provided, wherein N and M are integers; b) a row of N collimated light beams is created, said row of light beams being aligned with one of the rows of the array of vessels, such that each vessel in the row is illuminated by one collimated light beam; c) an (N+2) x 3 sensor array of light sensors is provided and arranged such that a middle row of the three rows of the sensor array is aligned with the vessels, wherein the first and last light sensor of said middle row are not positioned directly aligned with a vessel; d) a light intensity signal is generated by the individual sensors in the sensor array which are not directly aligned with a vessel and the corresponding collimated light beam; e) said light intensity signals of the individual sensors are fed as input signals to a signal processing unit; f
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Abstract
An optical sample analysing apparatus receives a vessel with a sample. The apparatus includes a light source for emitting a light beam through the vessel, a scatter light detector for detecting light scattered by the sample and a transmission light detector for detecting light transmission through the vessel. A signal processing unit connected to the transmission light detector and the scatter light detector determines the amount of light transmitted through the sample and the amount of light scattered by the sample. The apparatus comprises a sensor array of light sensors. The scatter light detector is formed by at least one light sensor comprised in said sensor array of light sensors, offset from the direction of the collimated light beam. The transmission light detector is formed by a light sensor comprised in said sensor array of light sensors, in line with the direction of the light beam.
Description
Title: Optical sample analysis and apparatus therefor
The present invention relates to an optical sample analysing apparatus, which in particular is suitable for use in nephelometry.
In nephelometry, a light beam is directed through a liquid sample containing suspended particles. The intensity of the scattered light at a specific angle is measured. The amount of scattering of the light by the sample is proportional to the concentration of particles in the sample.
In a known optical sample arrangement, a laser is used as a light source and the laser beam is directed through a vessel holding a sample. An integrating sphere, in the art also known as an Ulbricht sphere, is arranged in line, with the laser on the opposite side of the vessel such that a light inlet port of the integrating sphere can capture the light going through the vessel. A light exit port is located at an angle of 180° of the light inlet port of the sphere, at which exit port a light trap is arranged. The light trap catches the laser beam that is transmitted at 180° through the sphere. A further light exit port is arranged in the sphere at an angle different from 180°, for example at an angle of 90° with respect to the axis between the light inlet port and the exit port provided with the light trap. At this further light exit port a photodetector, e.g. a photodiode, is arranged. The photodetector is able to detect light that is reflected and diffused by the interior surface of the sphere. The light of the laser beam is partially scattered by particles in the sample. The laser beam that enters the sphere does not contribute to the scatter light detection because it is caught by the light trap. The amount of light detected by the photodetector is a measure for the scattering of the light, and thus is a measure for the amount of particles dissolved in the fluid, or in other words a measure for the turbidity of the sample.
Nephelometry is commonly used in various scientific and medical fields. It is for example widely used in clinical laboratories to measure the levels of specific proteins or other substances in bodily fluids. An example is a method disclosed in EP 2776840 B1 for determining the propensity of a fluid for calcification, using nephelometry in which the sample is excited by a laser beam. This method can be performed with an optical sample analysing apparatus comprising the arrangement including the laser and Ulbricht sphere as outlined in the above. An example of such a nephelometry apparatus is brought on the market by BMG Labtech under the name NEPHELOstar® Plus. In this known apparatus wells, i.e. small
vessels in which samples are contained, comprised in a well plate, can be aligned one at a time with the laser and the Ulbricht sphere to detect the amount of light scattered by the sample in that well.
The invention has for an object to provide an optical sample analysing apparatus which is more versatile and more efficient in use.
This object is achieved by an optical sample analysing apparatus comprising:
- a vessel receiving part for receiving a vessel containing a sample to be analysed,
- a light source configured and arranged to emit a collimated light beam through a vessel placed in the vessel receiving part,
- a scatter light detector configured and arranged to detect light scattered by the sample contained in said vessel,
- a transmission light detector to detect light transmission through said vessel,
- a signal processing unit connected to the transmission light detector and the scatter light detector for determining the amount of light transmitted through the sample and the amount of light scattered by the sample in said vessel, wherein the apparatus comprises a sensor array of light sensors, wherein the scatter light detector is formed by at least one light sensor comprised in said sensor array of light sensors, offset from the direction of the collimated light beam, and wherein the transmission light detector is formed by a light sensor comprised in said sensor array of light sensors, in line with the direction of the collimated light beam.
The apparatus according to the invention thus has a scatter light detector and a transmission light detector, whereby the apparatus can be used for analysing a sample via either scatter light detection, i.e. nephelometry, or transmission light detection. The apparatus also allows a combination of scatter light detection and transmission light detection. The transmission light detector is arranged 180° opposite the light source and allows detection of the amount of light of the collimated light beam that is transmitted through a vessel containing a sample. The amount of transmitted light may provide information about the state or contents of the sample. The scatter light detector is arranged at an angle other than 180° from the collimated light beam and allows detection of the amount of light that is scattered by the sample in the vessel. Advantageously the transmission light detector is formed by a light sensor comprised in a sensor array of light sensors, located 180° opposite the light source, i.e. aligned with the direction of the collimated light beam. The scatter light detector is formed by at least one light sensor comprised in the same sensor array of light sensors, located offset, from the direction of the collimated light beam, i.e. not 180° opposite the light source.
An Ulbricht sphere is omitted in the apparatus according to the invention, which is possible because of the detector lay-out in a sensor array as is proposed by the present invention.
In an embodiment of the optical sample analysis apparatus the signal processing unit is programmed to switch between multiple working modes, the working modes comprising:
- a scatter detection mode in which only an output signal of the scatter light detector is used,
- a transmission detection mode in which only an output signal of the transmission light detector is used,
- a combined mode in which the output signals of both the scatter light detector and the transmission light detector are used.
In this embodiment, in other words, the signal processing unit can select the output signals it uses in a certain working mode. In the scatter detection mode the output signal of the scatter light detector is selected, in the transmission detection mode the output signal of the transmission light detector is selected, and in the combined mode both mentioned output signals are selected. Thus, the scatter light detector and the transmission light detector both provide an output signal to the signal processing unit, which can processes both signals, but in the scatter detection mode the output signal of the transmission light detector is ignored by the signal processing unit, whereas in the transmission detection mode the output signal of the scatter light detector is ignored. In the combined mode none of the output signals of the scatter light detector and the transmission light detector is ignored by the signal processing unit, hence they are both used.
In a possible embodiment of the apparatus, the scatter light detector comprises eight sensors of a 3*3 sub-array except the central sensor of said 3*3 sub-array, or a selection of said eight sensors, wherein:
- in the scatter detection mode an output signal of the central sensor of the sub-array is ignored;
- in the transmission detection mode an output signal of the central sensor of the subarray is used as a transmission light detector signal representing light transmission through the vessel and the output signals of the surrounding eight sensors are ignored;
- in the combined mode an output signal of the central sensor of the sub-array is used as a transmission light detector signal representing light transmission through the vessel and the output signals of the surrounding eight sensors, or a selection thereof, are used as a scatter light detector signal representing scatter light by the vessel.
In an embodiment the scatter light detector comprises a plurality of light sensors. Preferably, the plurality of light sensors comprised in the scatter light detector form a sub-array of the sensor array of light sensors. The sub-array may for example be a square array of sensors. In a practical embodiment the sub-array is a 3x3 array of sensors, wherein the scatter light detector comprises the eight sensors of said sub-array except the central sensor of said subarray, the central sensor being positioned 180° opposite the light source. The scatter light detector may also be a selection of the mentioned eight sensors, for example the four sensors at the corner of the square sub-array.
In a possible embodiment the sensor array comprises multiple sub-arrays. Each sub-array may comprise a transmission detection sensor and a set of scatter detection sensors surrounding it. The sensor array thus comprises multiple transmission detectors and multiple scatter detectors by means of which multiple vessels can be analysed simultaneously.
In a further embodiment, adjacent sub-arrays overlap, i.e. some sensors are comprised in both of the adjacent sub-arrays.
In a practical embodiment the sensor array has (N+2) x 3 sensors, which is suitable for detecting light of a row of an N * M array of vessels, wherein N and M are integers. For example, in a practical embodiment N = 8 and M = 12. The sensor array has 10 x 3 light sensors, which together incorporate eight scatter detectors and eight associated transmission detectors. In such a configuration a sensor in the middle row of the three rows is comprised in the scatter detector associated with one vessel and is comprised in the transmission detector associated with the adjacent vessel in the row of vessels. In this way efficient use is made of the sensors in the sensor array.
In an embodiment each light sensor in the sensor array comprises at least one photodiode.
In a practical embodiment the photodiodes are arranged on a printed circuit board (PCB). In case of the above mentioned example a PCB with 3 rows of 10 photodiodes arranged on it is the result.
In a preferred embodiment the apparatus comprises a plurality of light sources. With a plurality of light sources a plurality of vessels can be illuminated and thus less movement of the vessels is necessary for analysing them. This improves the efficiency of the apparatus.
In a preferred embodiment the light source or light sources each comprise a light emitting diode (LED). Preferably the LED is a red light emitting diode.
In a further embodiment the LEDs are arranged on a printed circuit board (PCB).
In a possible embodiment the light source comprises at least one lens to collimate the light beam incident on the vessel.
In a possible embodiment the light source comprises a lens stack to collimate the light beam. With a lens stack the light of a LED can be collimated to a collimated beam that is directed through the vessel containing a sample to be analysed.
The lens stack may further comprise one or more light traps. The one or more light traps catch the light that is not going through the lens(es) and reduces stray light which facilitates collimating the light beam.
The receiving part comprises a holder for holding a well plate comprising an array of wells, the wells forming the vessels for holding samples. Such a well plate may have an array of N x M wells, wherein N and M are the same integers as described in the above. Such a well plate can be combined with the feature that the light sources of the apparatus comprise a row of LEDs on a printed circuit board (PCB), wherein the number of LEDs is N.
Alternatively, the receiving part may comprise a holder for holding one or more cuvettes, the cuvettes forming the vessels for holding samples.
The invention furthermore relates to a nephelometry apparatus comprising an optical sample analysis apparatus as described in the above.
The invention also relates to the use of an optical sample analysis apparatus as described in the above in nephelometry.
The invention furthermore relates to the use of an optical sample analysis apparatus as described in the above in a method for determining the propensity of a fluid for calcification.
The invention also relates to a nephelometry method comprising the following method steps: a) An N x M array of vessels each holding a sample comprising a liquid is provided, wherein N and M are integers;
b) a row of N collimated light beams is created, said row of light beams being aligned with one of the rows of the array of vessels, such that each vessel in the row is illuminated by one collimated light beam; c) an (N+2) x 3 sensor array of light sensors is provided and arranged such that a middle row of the three rows of the sensor array is aligned with the vessels, wherein the first and last light sensor of said middle row are not positioned directly aligned with a vessel; d) a light intensity signal is generated by the individual sensors in the sensor array which are not directly aligned with a vessel and the corresponding collimated light beam; e) said light intensity signals of the individual sensors are fed as input signals to a signal processing unit; f) the signal processing unit computes the scatter light per vessel in the row from the input signals and computes a corresponding concentration of suspended particles in the liquid of the sample; g) the array of vessels is moved relative to the row of collimated light beams and the array of sensors, or vice versa, such that another row of vessels of the array of vessels is aligned with the row of collimated light beams and the middle row of the array of sensors; h) the steps d-g are repeated until the whole array of vessels is analysed at least once.
The invention also relates to a method for determining the propensity of a fluid for calcification, comprising the nephelometry method as described above.
The invention will be further elucidated with reference to the drawings, in which:
Fig.1 shows schematically a cross section of an optical sample analysing apparatus according to the invention,
Fig. 2 shows schematically a bottom elevational view of a PCB with LEDs of the apparatus of Fig. 1 ,
Fig. 3 shows schematically a top elevational view of a PCB with an array of photodiodes of the apparatus of Fig. 1 ,
Fig. 4 shows a top elevational view of a well plate to be arranged in the apparatus of Fig. 1 and the schematical sensor array of Fig. 3,
Fig. 5 shows schematically a top elevational view of the array of photodiodes of Fig. 3 with a row of wells aligned with it,
Fig. 6 illustrates a scatter light detection at a first well of the row of wells of Fig. 5,
Fig. 7 illustrates a scatter light detection at a second well of the row of wells of Fig. 5,
Fig. 8 illustrates the overlap between adjacent subarrays of the array of photodiodes of Fig. 5.
Fig. 1 shows an optical sample apparatus 1. The optical sample apparatus 1 generally comprises a light source block 2, a receiving means for a well plate 4 and a sensor unit 6.
The light source block 2 comprises a housing 20 in which a row of tubular cavities 24 is formed. In each of the tubular cavities 24 a lens stack 21 is provided. In this particular embodiment eight lens stacks 21 are provided. Each lens stack 21 comprises a stack of light trap chambers 23a, 23b and 23c, respectively, which have a collimating lens 22a, 22b and 22c, respectively, which is arranged at one axial end of the light trap chamber 23a, 23b, 23c. At a bottom end of the tubular cavity 24 a further lens 25 is arranged. The lens 25 is kept in place by a bottom plate 26 which is attached to the housing 20. The bottom plate 26 is provided with openings 27 at the lenses 25 to allow light collimated by the light stacks to exit the housing 20 as collimated light beams.
The light source block 2 furthermore comprises a LED plate 3 which is arranged at a top end of the housing and attached to the housing by fasteners, in this embodiment the fasteners are screws 50. A gasket 51 is arranged between the housing 20 and the LED plate 3, which inhibits light to enter from the exterior through the interface between the LED plate 3 and the housing 20 into the interior of the housing 20, in particular into the tubular cavities 24. The LED plate 3 comprises a printed circuit board (PCB) 30 which is provided with a row of light emitting diodes (LEDs) 31 , as is shown in Figs 1 and 2. The number of LEDs 31 in the row corresponds to the number of tubular cavities 24 and corresponding lens stacks 21. The LEDs 31 are arranged such that each of them is positioned at a respective top end of the tubular cavities 24.
The LEDs 31 are all the same and are preferably emitting red light.
Below the light source block 2, at a distance from the bottom plate 26, a sensor unit 6 is arranged. The sensor unit 6 comprises a printed circuit board (PCB) 60 with an array 61 of photodiodes 62 arranged on the PCB as is illustrated in Fig. 3. In the shown embodiment the array 61 has three rows, which are illustrated in Fig. 3 by a dashed box drawn around the photodiodes and indicated by reference numerals 63a, 63b and 63c, respectively. Each of the rows 63a, 63b, 63c in this example has ten photodiodes 62. The middle row 63b is arranged in line with the row of LEDs and the corresponding lens stacks 21.
The photodiodes 62 are connected with a signal processing unit 9, shown schematically in Fig. 3. The signal processing unit 9 may be arranged on the PCB 60 or may be incorporated in another component or device, e.g. comprised in a computer.
Between the bottom plate 26 and the sensor unit 6 an intermediate receiving space 7 is provided in which a well plate 4 can be arranged. In Fig. 1 a state is illustrated in which the well plate 4 is placed in said intermediate space 7 in the machine. The receiving space 7 is comprised in a receiving part of the machine, which may comprise holding means for holding the well plate 4 and a moving mechanism for moving the well plate 4 with respect to the light source block 2 and the sensor unit 6.
A top elevational view of the well plate 4 and the array 61 of photodiodes 62 (cf. Fig. 3) is shown in Fig. 4. The well plate 4 has an array of wells 41. The well plate 4 shown here has an array of 8*12 wells 41 . The vertically drawn rows of eight wells 41 are aligned parallel with the row of LEDs on the LED plate 3. The well plate 4 is movable in the intermediate space 7 with respect to the light source block 2 and the sensor unit 6, according to an arrow 8 indicated in Fig. 4. In this way a row of wells 41 can be moved and aligned with the row of LEDs / lens stacks, and with the row 63b of photodiodes 62.
In a practical, commercially available embodiment, the wells 41 are vessels having a diameter of about 5 mm and a height of about 10 mm. In use the wells 41 can each hold a sample to be analysed. The wells 41 have a wall that allows transmission of light therethrough and have an open top end through which the sample can be injected in the well 41 .
In use the wells 41 are filled with a liquid sample. The well plate 4 is moved through the intermediate space 7 such that the rows, i.e. the vertical rows indicated 1-12 in Fig. 4 are consecutively aligned with the row of light sources and the centre row 63b of photodiodes 62. In Fig. 5 is illustrated schematically how a row of wells 41 is aligned with the centre row 63b of the array of photodiodes.
To explain the working of the device, as an example, the first well 41 of the row is taken which may be the well 41 indicated in Fig. 4 by A1, cf. Fig. 6. Light is emitted by the LED 31 through the lens stack 21 and is emitted as a collimated light beam into the well 41-A1. The light of the beam entering the sample is detectable by a subarray of photodiodes 62, which subarray is illustrated by a dotted box indicated with reference numeral 64A in Fig. 6. The subarray 64A is a square array which includes nine photodiodes 62. The central photodiode 62CA of this subarray 64 (see Fig. 6) can detect the light beam that goes straight through the sample in the well 41-A1.
The sample in the well 41-A1 may cause scattering of the light. This scattered light is detectable by the photodiodes 62’ of the subarray 64A which are offset from the direction of the collimated light beam. In Fig. 6 these photodiodes 62’ are shaded and surround the central photodiode 62CA of the subarray 64A. The intensity of the scattered light at a specific angle can be measured with the photodiodes 62’. The amount of scattering of the light by the sample in the well 41 -A1 is proportional to the concentration of particles in the sample and can be detected by the shaded photodiodes 62’ in Fig. 6. Thus the detected light by the photodiodes 62’ is a measure of the amount of particles in the sample, which may provide information about the composition of the sample. The photodiodes 62’ of the subarray 64A thus function together as a scatter light detector for the well 41-A1.
The central photodiode 62CA may be used as a transmission light detector to detect light transmission through the vessel 41-A1.
As described in the above the scatter light detector comprises eight sensors of a 3*3 subarray 64A except the central sensor 62CA of said 3*3 sub-array. Instead of all sensors 62’ also a selection of said eight sensors 62’ can be used for the scatter light detection.
The signal processing unit 9 is preferably programmed to switch between multiple working modes. These working modes may comprise a scatter detection mode in which only an output signal of the scatter light detector is used, and a transmission detection mode in which only an output signal of the transmission light detector is used. Also a combined mode is possible in which the output signals of both the scatter light detector and the transmission light detector are used. In a possible embodiment, in the scatter detection mode, an output signal of the central photodiode of the sub-array 64A is ignored and the output signals of the surrounding eight photodiodes 62’, or a selection thereof, are used as a scatter light detector signal representing scatter light by the well 41-A1. In the transmission detection mode an output signal of the central photodiode of the sub-array 64A is used as a transmission light
detector signal representing light transmission through the well 41 -A 1 and the output signals of the surrounding eight photodiodes 62’ are ignored. In the combined mode an output signal of the central photodiode 62CA of the sub-array 64A is used as a transmission light detector signal representing light transmission through the well 41 -A1 and the output signals of the surrounding eight photodiodes 62’, or a selection thereof, are used as a scatter light detector signal representing scatter light by the well 41-A1.
The signal processing unit 9 provides measurement values of the scatter light detector and/or the transmission light detector. The signal processing unit is programmed to convert these measurement values to metrics about the composition of the sample. In another embodiment the signal processing unit may communicate with a computer that determines the metrics about the composition of the sample.
In the same way as in the above, the sample in the well 41 indicated in Fig. 4 by B1 can be analysed. Light is emitted by the LED 31 through the lens stack 21 and is emitted as a collimated light beam into the well 41-B1. The light of the beam entering the sample is detectable by a subarray of photodiodes 62, which subarray is illustrated by a dotted box indicated with reference numeral 64B in Fig. 7. The subarray 64B is a square array which includes nine photodiodes 62”. The central photodiode 62CB of this subarray 64B (see Fig. 7) can detect the light beam that goes straight through the sample in the well 41 -B1 .
The sample in the well 41-B1 may cause scattering of the light. This scattered light is detectable by the photodiodes 62” of the subarray 64B which are offset from the direction of the collimated light beam. In Fig. 7 these photodiodes 62” are shaded and surround the central photodiode 62CB of the subarray 64B. The intensity of the scattered light at a specific angle can be measured with the photodiodes 62”. The amount of scattering of the light by the sample in the well 41 -B1 is proportional to the concentration of particles in the sample and can be detected by the shaded photodiodes 62” in Fig. 7. Thus the detected light by the photodiodes 62” is a measure of the amount of particles in the sample, which may provide information about the composition of the sample. The photodiodes 62” of the subarray 64B thus function together as a scatter light detector for the well 41 -B1.
The central photodiode 62CB may be used as a transmission light detector to detect light transmission through the vessel 41-B1.
Comparison of Figs 6 and 7 shows that light passing through the wells 41-A1 and 41-B1 is detected with partially the same photodiodes. This is illustrated in Fig. 8, which show that the
subarrays 64A and 64B are overlapping. The photodiodes in the overlap, i.e. the photodiodes that are comprised in both of the adjacent sub-arrays 64A and 64B, are depicted with a dotted pattern in Fig. 8. The photodiode indicated in Fig. 8 with the reference numerals 62CA, 62” is when used in the array 64A for detection of light of the well 41 -A1 a central photodiode, which can be used as a transmission detector, whilst when used in the array 64B for detection of light of the well 41-B1 it is one of the photodiodes 62” of the scatter detector.
In order to be able to make an individual scatter detection for the wells 41-A1 to 41-H1 (cf. Fig. 4) in one row, the LEDs 31 in the row of LEDs are activated consecutively, whereby the subarrays 64A, 64B, ... , 64H, are correspondingly used to detect scatter and/or transmission of light. By making use of overlapping subarrays efficient use is made of the photodiodes in the sensor array and the number of photodiodes necessary is reduced, which provides a cost effective solution.
After the wells in the entire row have been illuminated and the detector signals have been captured, for example in a computer memory, the well plate 4 can be moved in the direction 8, whereby the next row, i.e. the row of wells A2 to H2 in Fig. 4, is positioned underneath the row of LEDs 31 and associated lens stacks 21, and above the middle row 63b of photodiodes 62, after which the above described process is executed again. This can be repeated until all rows (vertical rows 1-12 in Fig. 4) are measured.
The above optical sample analysis apparatus 1 can be used in a nephelometry apparatus.
In more general terms, the optical analysis apparatus can be adapted and configured to perform a nephelometry method comprising the following method steps: a) An N * M array of vessels each holding a sample comprising a liquid is provided, wherein N and M are integers; b) a row of N collimated light beams is created, said row of light beams being aligned with one of the rows of the array of vessels, such that each vessel in the row is illuminated by one collimated light beam; c) an (N+2) x 3 sensor array of light sensors is provided and arranged such that a middle row of the three rows of the sensor array is aligned with the vessels, wherein the first and last light sensor of said middle row are not positioned directly aligned with a vessel; d) a light intensity signal is generated by the individual sensors in the sensor array which are not directly aligned with a vessel and the corresponding collimated light beam;
e) said light intensity signals of the individual sensors are fed as input signals to a signal processing unit; f) the signal processing unit computes the scatter light per vessel in the row from the input signals and computes a corresponding concentration of suspended particles in the liquid of the sample; g) the array of vessels is moved relative to the row of collimated light beams and the array of sensors, or vice versa, such that another row of vessels of the array of vessels is aligned with the row of collimated light beams and the middle row of the array of sensors; the steps d-g are repeated until the whole array of vessels is analysed at least once.
Claims
1. Optical sample analysing apparatus comprising:
- a vessel receiving part for receiving a vessel containing a sample to be analysed,
- a light source configured and arranged to emit a collimated light beam through a vessel placed in the vessel receiving part,
- a scatter light detector configured and arranged to detect light scattered by the sample contained in said vessel,
- a transmission light detector to detect light transmission through said vessel,
- a signal processing unit connected to the transmission light detector and the scatter light detector for determining the amount of light transmitted through the sample and the amount of light scattered by the sample in said vessel, wherein the apparatus comprises a sensor array of light sensors, wherein the scatter light detector is formed by at least one light sensor comprised in said sensor array of light sensors, offset from the direction of the collimated light beam, and wherein the transmission light detector is formed by a light sensor comprised in said sensor array of light sensors, in line with the direction of the collimated light beam.
2. Optical sample analysis apparatus according to any one of the preceding claims, wherein the signal processing unit is programmed to switch between multiple working modes, the working modes comprising:
- a scatter detection mode in which only an output signal of the scatter light detector is used,
- a transmission detection mode in which only an output signal of the transmission light detector is used,
- a combined mode in which the output signals of both the scatter light detector and the transmission light detector are used.
3. Optical sample analysis apparatus according to claim 1 or 2, wherein the scatter light detector comprises a plurality of light sensors.
4. Optical sample analysis apparatus according to claim 3, wherein the plurality of light sensors comprised in the scatter light detector form a sub-array of said sensor array of light sensors.
5. Optical sample analysis apparatus according to claim 4, wherein the sub-array is a square array of sensors.
6. Optical sample analysis apparatus according to claim 5, wherein the sub-array is a 3x3 array of sensors, and wherein the scatter light detector comprises the eight sensors of said sub-array except the central sensor of said sub-array, or a selection thereof.
7. Optical sample analysis apparatus according to claim 2, wherein the scatter light detector comprises eight sensors of a 3x3 sub-array except the central sensor of said 3x3 sub-array, or a selection of said eight sensors, and wherein:
- in the scatter detection mode an output signal of the central sensor of the sub-array is ignored,
- in the transmission detection mode an output signal of the central sensor of the subarray is used as a transmission light detector signal representing light transmission through the vessel and the output signals of the surrounding eight sensors are ignored;
- in the combined mode an output signal of the central sensor of the sub-array is used as a transmission light detector signal representing light transmission through the vessel and the output signals of the surrounding eight sensors, or a selection thereof, are used as a scatter light detector signal representing scatter light by the vessel.
8. Optical sample analysis apparatus according to any one of the claims 4-7, wherein the sensor array comprises multiple sub-arrays.
9. Optical sample analysis apparatus according to claim 8, wherein adjacent sub-arrays overlap, i.e. some sensors are comprised in both of the adjacent sub-arrays.
10. Optical sample analysis apparatus according to claim 9, wherein the sensor array has (N+2) x 3 sensors, which is suitable for detecting light of a row of an N x M array of vessels, wherein N and M are integers.
11 . Optical sample analysis apparatus according to any one of the preceding claims, wherein each light sensor in the sensor array comprises at least one photodiode.
12. Optical sample analysis apparatus according to claim 11 , wherein the photodiodes are arranged on a printed circuit board (PCB).
13. Optical sample analysis apparatus according to any one of the preceding claims, wherein the apparatus comprises a plurality of light sources.
14. Optical sample analysis apparatus according to any one of the preceding claims, wherein the light source or light sources each comprise a light emitting diode (LED).
15. Optical sample analysis apparatus according to claim 14, wherein each LED is a red light emitting diode.
16. Optical sample analysis apparatus according to any one of the claims 14-15, wherein the LED or LEDs are arranged on a printed circuit board (PCB).
17. Optical sample analysis apparatus according to any one of the preceding claims, wherein the light source comprises at least one lens to collimate the light beam incident on the vessel.
18. Optical sample analysis apparatus according to claim 17, wherein the light source comprises a lens stack to collimate the light beam.
19. Optical sample analysis apparatus according to claim 18, wherein the lens stack comprises one or more light traps.
20. Optical sample analysis apparatus according to any one of the preceding claims, wherein the receiving means comprises a holder for holding a well plate comprising an array of wells, the wells forming the vessels for holding samples.
21 . Optical sample analysis apparatus according to claim 20, wherein the well plate has an array of N * M wells.
22. Optical sample analysis apparatus according to any one of the claims 1-19, wherein the receiving part comprises a holder for holding one or more cuvettes, the cuvettes forming the vessels for holding samples.
23. Optical sample analysis apparatus according to claim 21 , wherein the light sources comprise a row of LEDs on a printed circuit board (PCB), wherein the number of LEDs is N.
24. Nephelometry apparatus comprising an optical sample analysis apparatus according to any one of the preceding claims.
25. Use of an optical sample analysis apparatus according to any one of the claims 1-23 in nephelometry.
26. Use of an optical sample analysis apparatus according to any one of the claims 1-23 in a method for determining the propensity of a fluid for calcification.
27. Nephelometry method comprising the following method steps: h) An N x M array of vessels each holding a sample comprising a liquid is provided, wherein N and M are integers; i) a row of N collimated light beams is created, said row of light beams being aligned with one of the rows of the array of vessels, such that each vessel in the row is illuminated by one collimated light beam; j) an (N+2) x 3 sensor array of light sensors is provided and arranged such that a middle row of the three rows of the sensor array is aligned with the vessels, wherein the first and last light sensor of said middle row are not positioned directly aligned with a vessel; k) a light intensity signal is generated by the individual sensors in the sensor array which are not directly aligned with a vessel and the corresponding collimated light beam; l) said light intensity signals of the individual sensors are fed as input signals to a signal processing unit; m) the signal processing unit computes the scatter light per vessel in the row from the input signals and computes a corresponding concentration of suspended particles in the liquid of the sample; n) the array of vessels is moved relative to the row of collimated light beams and the array of sensors, or vice versa, such that another row of vessels of the array of vessels is aligned with the row of collimated light beams and the middle row of the array of sensors; o) the steps d-g are repeated until the whole array of vessels is analysed at least once.
28. A method for determining the propensity of a fluid for calcification, comprising the nephelometry method according to claim 27.
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|---|---|---|---|
| NL2037708 | 2024-05-16 | ||
| NL2037708A NL2037708B1 (en) | 2024-05-16 | 2024-05-16 | Optical sample analysis and apparatus therefor |
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| WO2025238032A1 true WO2025238032A1 (en) | 2025-11-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2025/063120 Pending WO2025238032A1 (en) | 2024-05-16 | 2025-05-14 | Optical sample analysis and apparatus therefor |
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| NL (1) | NL2037708B1 (en) |
| WO (1) | WO2025238032A1 (en) |
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| US20030010941A1 (en) * | 2000-02-24 | 2003-01-16 | Reiner Spolaczyk | Optical measuring system |
| US20150160118A1 (en) * | 2013-12-06 | 2015-06-11 | BacterioScan Inc. | Method And System For Optical Measurements Of Contained Liquids Having A Free Surface |
| EP2776840B1 (en) | 2011-11-07 | 2016-02-03 | Rheinisch-Westfälische Technische Hochschule Aachen | A method for determining the propensity for calcification |
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2024
- 2024-05-16 NL NL2037708A patent/NL2037708B1/en active
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2025
- 2025-05-14 WO PCT/EP2025/063120 patent/WO2025238032A1/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09189654A (en) * | 1996-01-11 | 1997-07-22 | Horiba Ltd | Scattering type particle size distribution measuring device |
| US20030010941A1 (en) * | 2000-02-24 | 2003-01-16 | Reiner Spolaczyk | Optical measuring system |
| EP2776840B1 (en) | 2011-11-07 | 2016-02-03 | Rheinisch-Westfälische Technische Hochschule Aachen | A method for determining the propensity for calcification |
| US20150160118A1 (en) * | 2013-12-06 | 2015-06-11 | BacterioScan Inc. | Method And System For Optical Measurements Of Contained Liquids Having A Free Surface |
Non-Patent Citations (1)
| Title |
|---|
| BRANDON BERG ET AL: "Cellphone-Based Hand-Held Microplate Reader for Point-of-Care Testing of Enzyme-Linked Immunosorbent Assays", ACS NANO, vol. 9, no. 8, 25 August 2015 (2015-08-25), US, pages 7857 - 7866, XP055335836, ISSN: 1936-0851, DOI: 10.1021/acsnano.5b03203 * |
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| Publication number | Publication date |
|---|---|
| NL2037708B1 (en) | 2025-11-25 |
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