NL2002368C2

NL2002368C2 - System and method for simultaneously performing phase behaviour tests on a plurality of samples.

Info

Publication number: NL2002368C2
Application number: NL2002368A
Authority: NL
Inventors: Emilio Rene Bodenstaff; Benjamin Mckay; Erik-Jan Ras
Original assignee: Avantium Holding B V
Priority date: 2008-12-05
Filing date: 2008-12-23
Publication date: 2010-06-08

Description

P29681NL00/NBL

System and method for simultaneously performing phase behaviour tests on a plurality of samples

The invention pertains to a system and a method for simultaneously performing phase behaviour tests on a plurality of samples, in particular for performing such tests in a high 5 throughput setting, in which multiple tests are carried out simultaneously.

Phase behaviour tests come in many different varieties. Stability tests and instability tests are one group of phase behaviour tests. In stability tests or instability tests substances, such as emulsions, dispersions, colloids, suspensions and the like are tested. It could be that those substances comprise one ore more dispersed phases that are dispersed in a 10 continuous phase, but it is also possible that for example the droplets in an emulsion are so fine and homogenously distributed (like for example in cosmetic products) that the substance has the appearance of a single phase at the beginning of the stability test. Over time, phase separation can occur, for example in the form of creaming, sedimentation, flocculation, and/or coalescence. If this occurs, layers of different phases may be formed in the substance and/or 15 the size of the entities of a phase (e.g. droplets or particles) may change. Stability testing and/or instability testing are for example directed to observing for example whether phase separation occurs, whether changes in particle size of a dispersed phase occur, how long the process of separation takes to start, and what form it takes, and/or whether layers of different phases are formed or not.

20 Phase behaviour tests in the sense of the invention do not only involve liquid and/or solid phases; also one or more gaseous phases can be involved. For example, the formation of gas bubbles is a process that can be studied in phase behaviour tests. In another example, the evaporation of a liquid can be monitored by monitoring the position of liquid surface or a gas/liquid phase interface in the vial.

25 Phase behaviour tests often are directed to studying the phase behaviour of a substance as a function of time. However, phase behaviour studies also include tests in which the phase behaviour is studied as a function of composition and/or changes in composition. Phase behaviour tests can also be used to study mixing and de-mixing of substances or for solubility tests. Phase behaviour tests can be used for observing slowly 30 progressing processes as well as for observing fast processes. The samples of substances to be studied can comprise one or more phases at the start of the test, and the number of phases can increase, decrease or stay the same during the tests. If multiple phases are present at some point in the test, their distribution over the sample can be monitored for the -2- occurrence of changes. The same applies to the size of any particles or droplets in the sample.

High throughput experiments involving the simultaneous performance of multiple tests are generally known in for example screening of catalyst libraries or for use in drug discovery 5 in the pharmaceutical industry.

International application W02004/053468 describes a device and method for performing a plurality of stability tests on samples containing a dispersion of one or more incompletely miscible components. In the method and apparatus as described in this document, a plurality of transparent vials are provided with a sample to be tested. The vials 10 are arranged in an array. A robot arm takes the vials one by one to a position in front of a camera, which records an image of the contents of the vial. Then, the vial is put back into the array, and the robot arm takes the next vial to the position in front of the camera. This is repeated for all of the vials, and optionally each of the vials is positioned in front of the camera multiple times. Image processing software analyses the images taken by the camera 15 and for example phase interfaces are identified so that the evolution over time of the disperse systems can be monitored. The device according to WO 2004/053468 has a single camera.

US 4,710,874 describes a method and apparatus for displaying particle sedimentation rates in liquids, such as blood. In the device according to this document, a plurality of light-transparent containers is provided. Each container can hold a sample of blood or the like. The 20 containers are arranged in a rotary support. A single camera with image processing equipment is present. By means of stepwise rotation, the rotary support brings the containers one-by-one in front of the camera.

These know devices and methods have several drawbacks. A first drawback is that the vial with the sample has to be moved before it is in a position in which the camera can record 25 the image. The movement of the vial can disturb for example the sedimentation, creaming or flocculation process that takes place in the sample, which leads to inaccuracy of the measurement. A second drawback is that the recording of the images takes place sequentially. This limits the number of samples that can be tested per unit of time in a single system. Furthermore, it is not possible to compare the state of all samples at a certain 30 moment is time as simultaneous measurements on different samples are not possible with the known system. An other problem is that some processes relating to phase behaviour take place very quickly. For example this is the case in sedimentation processes in water-oil-sediment, like in tar sand related substances. Such processes may well be over before the relevant vial is put in front of the single detector.

The invention seeks to provide an improved method and system for simultaneously performing phase behaviour tests on a plurality of samples.

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This object is achieved with a system according to claim 1, a system according to claim 10, and a method according to claim 15 and a method according to claim 19.

If one would like to increase the number of samples that can be tested per unit of time in a single system, one could - instead of providing a single detector -provide a plurality of 5 detectors, so that images of multiple vials can be recorded simultaneously. This indeed increases the number of samples that can be tested per unit of time, but it also gives rise to a practical problem.

Even when simple cameras such as webcams or low resolution mobile phone cameras are used as image sensors, the image sensors together produce an enormous amount of 10 data that has to be processed. In common high throughput set-ups, it is often desirable to simultaneously test 16 samples or more. This would mean that either multiple computers have to be provided, which increases the costs of the system significantly or that the performance of the system as such would be compromised due to the low data transfer rate.

The invention provides two ways in which these high costs and/or poor performance 15 can be avoided. The first way is with a system according to claim 1 and a method according to claim 15. According to the invention, each vial is arranged within the visual field of at least one detector, so image data can be obtained from all vials simultaneously or at least substantially simultaneously. It can be that multiple vials are arranged within the visual field of a single detector, or that each vial has an dedicated detector of its own. Each detector has an 20 image sensor, for example a sensor with a CCD-chip or a CMOS-chip. The image data coming from a detector is transferred to a data buffer, in which it is stored. The data buffer can be for example a SDRAM memory card.

The image processor retrieves image data from the data buffer. It can do so at its own pace, and in practice it may not retrieve all image data from the data buffer, but only a limited 25 amount of data sets, each data set for example together forming one “snap-shot” of a particular vial. The image processor is adapted to transform said image data into a format that allows analysis of the image data, in particular with respect to any kind of phase behaviour that takes place in the vial. Image analysis software can be provided so that the analysis takes place automatically. In a less sophisticated embodiment, the image processor merely 30 transforms the image data retrieved from the data buffer into visual information, that can be analysed by a human operator.

Often, phase behaviour tests require that it is monitored what is happing in the vial during a certain period of time. In order to do this, the system and the method according to the invention allow that multiple image data sets of the same vial are retrieved and analysed. 35 Those image sets are of course taken at different moments in time, so that for example the development of phase layers can be monitored and studied.

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Phase interfaces between phase layers, particle boundaries and/or gas-liquid interfaces can be detected in various ways. If the substance in the vial is such that the different phases have different colours, this can easily be detected by general image analysis equipment that interprets the data coming from a CCD-chip or CMOS-chip. In such cases, for example a chip 5 from a mobile phone camera or from a webcam could be used.

However, the invention is not limited to detectors having such image sensors. Different phases being present or developing can also be detected in other ways, for example by using infrared or ultraviolet radiation or spectrography such as RAMAN-analysis. It is possible to use image sensors that are sensitive to visible light, but instead or in addition, also image 10 sensors that are sensitive to for example ultraviolet radiation, infrared radiation, near-infrared radiation or other types of radiation (gamma, X-ray) can be used.

An other type of detector can use a combination of one or more light sources (in the infrared, near-infrared, visual and/or ultraviolet range) and a plurality of photosensors. The light sources and the photosenors can be arranged on opposite sides of the vial, so that 15 differences in transparency can be detected. For more opaque substances, the photosensors can be arranged on the same side of the vial as the light sources, so that back scatter can be measured. Other configurations are also possible.

In an advantageous embodiment, the system comprises programmable hardware component component or a high performance processor, for example a Field Programmable 20 Gate Array (FPGA), which directs image data from one or more of the detectors to a data buffer. The system can have one or more data buffers. Preferably, the image processor obtains the image data from the data buffer also via the programmable hardware component component or high performance processor. This can be the same hardware component (for example an FPGA-chip) or a different one.

25 In an advantageous embodiment, the programmable hardware component or high performance processor is programmed to detect changes in the image data received from a certain detector. This information can be used in the control of the system. For example, if changes start to occur, for example due to the forming of phase layers or gas bubbles, the control system that is present to control the test system can make the image processor to 30 retrieve more image data per unit of time relating to that particular vial from the data buffer. This way, the changes in that vial can be monitored more closely.

The changes occurring in the vial that are detected by the programmable hardware component or high performance processor (or the absence of such changes) can also trigger other actions, like activating or de-activating a stirrer and/or a heater or cooler, the addition of 35 a fluid, the triggering of a visible or audible alarm and/or the stop of the test.

In a further advantageous embodiment, the programmable hardware component or high performance processor can be programmed to perform calculations on the image data -5- received from the one or more detectors to which it is connected. For example, the (change in) particle size and/or droplet size of a dispersed phase can be detected. An increase in particle size and/or droplet size may point to flocculation or coalescence. An other option is that the thickness of a phase layer is calculated, or the changes in such thickness, or in case 5 of gas bubbles, the velocity at which they move to the surface.

This information can also be used in the control of the system, like changing the frequency of the image retrieval by the image processor, activating or de-activating a stirrer, activating or de-activating a heater or cooler, the addition of a fluid, the triggering of a visible or audible alarm and/or the stop of the test.

10

In a second way in which the high costs for data processing can be avoided and/or the performance of the system can be increased, use is made of two detectors per vial. A primary detector is a detector with a relatively low bit rate, which means that it does not produce much data per unit of time. For example, this could be a combination of one or more light sources 15 with one or more photodetectors. The primary detector is used to monitor whether changes take place in the substance in the vial. Once a certain level of change starts occurs, the secondary detector is activated. This secondary detector is a detector with a high bit rate, which means that it generates much data per unit of time. Such a detector could comprise a CCD-chip or CMOS-chip, sensitive to visible light, infrared radiation, near infrared radiation 20 and/or ultraviolet radiation.

This set-up has the advantage that only when something of interest occurs in the vial, a large amount of data is produced. This lowers the demand on the data handling capacities of the system and allows to monitor vials in parallel.

Components similar to those of the system with the data buffer according to the 25 invention as described above and its embodiments work in a similar or the same way, as will be understood by the skilled person

In an advantageous embodiment, a system with a primary and secondary detector according to the invention is further provided with a data buffer like in the system according to claim 1. Also, the other features of the system with the data buffer can be incorporated in this 30 system with a primary and secondary detector according to the invention, such as the programmable hardware component or high performance processor.

The invention will be explained in more detail under referral to the drawing, in which 35 non-limiting embodiments of the invention are shown. The drawing shows in:

Fig. 1a-e: possible processes that may occur during phase behaviour testing,

Fig. 2a-d: possible set-ups of the system and method according to the first option, -6-

Fig. 3a : an example of a picture that is produced from an image data set obtained by a detector that has one vial in its field of vision,

Fig. 3b : an example of a picture that is produced from an image data set obtained by a detector that has three vials in its field of vision, 5 Fig. 4: a preferred embodiment,

Fig. 5: a variant of the embodiment of fig. 4,

Fig. 6: an embodiment of the second option,

Fig. 7: A system combining the embodiments of fig. 4 and fig. 6.

10 Fig. 1 a, 1 b, 1 c, 1 d and 1 e show schematically some of the processes that may occur during phase behaviour testing.

Fig. 1 a-1 shows the start of a first example of a phase behaviour experiment. In this example, a vial 10 is provided with a multiphase substance 1, having a dispersed phase 2 and a continuous phase 3, for example an oil-in-water emulsion or a water-in-oil emulsion.

15 The dispersed phase 2 is substantially homogenously dispersed in the continuous phase 3. After some time, for example 0.1 seconds or 15 minutes, phase separation begins to take place. This is shown in fig. 1a-2. In this example, the phase separation takes the form of creaming, which means that the dispersed phase collects on top of the continuous phase.

Fig. 1a-2 shows that in the lower part of the vial 10, the amount of the dispersed phase 2 is 20 decreasing, while in the upper part of the vial 10 it increases. Phase layers, that is layers is which one phase is predominant, start to form. Fig. 1 a-3 shows the situation at the end of the test, for example after 5 seconds or an hour. Now clearly two phase layers are visible, with the dispersed phase on top and the continuous phase below it. The two layers are separated by a phase interface 4.

25 Fig. 1 b-1 shows the start of a second example of a phase behaviour experiment. In this case again, a vial 10 is provided with a multiphase substance 1, having a dispersed phase 2 and a continuous phase 3. The dispersed phase 2 is substantially homogenously dispersed in the continuous phase 3. After some time, for example 0.1 seconds or 15 minutes, phase separation begins to take place. This is shown in fig. 1 b-2. In this example, the phase 30 separation takes the form of sedimentation, which means that the dispersed phase collects at the bottom of the vial. Fig. 1 b-2 shows that in the upper part of the vial 10, the amount of the dispersed phase 2 is decreasing, while in the lower part of the vial 10 it increases. Phase layers start to form. Fig. 1 b-3 shows the situation at the end of the test, for example after 5 seconds or an hour. Now clearly two phase layers are visible, with the dispersed phase at the 35 bottom and the continuous phase on top of it. The two layers are separated by a phase interface 4.

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Fig. 1 c-1 shows the start of a third example of a phase behaviour experiment, at which again a vial 10 is provided with a multiphase substance 1, having a dispersed phase 2 and a continuous phase 3. The dispersed phase 2 is substantially homogenously dispersed in the continuous phase 3. After some time, for example 0.1 seconds or 15 minutes, phase 5 separation begins to take place. This is shown in fig. 1 c-2. In this example, the phase separation takes the form of flocculation or coalescence, which means that the particles or droplets of the dispersed phase increase in size. Fig. 1 c-3 shows the situation at the end of the test, for example after 5 seconds or an hour. Now the size of the particles or droplets of the dispersed phase has come to a maximum size, but they remain distributed in the 10 continuous phase. In this case, phase interfaces are present around all individual particles and/or droplets of the dispersed phase.

Fig. 1 d-1 shows the start of a fourth example of a phase behaviour experiment, in this case a crystallisation experiment. A vial 10 is provided with a liquid 102 and a powder 103, that are separated from each other by phase interface 104. The vial 10 is heated and gas 15 bubbles 105 start to form, due to the evaporation of the liquid. This is shown in fig. 1d-2. As fig. 1 d-3 shows, the gas bubbles 105 move to the surface 106 of the liquid 102 and escape. The liquid surface 106 comes to lie at a lower level in the vial 10, due to this evaporation of liquid. Some of the powder 103 dissolves in the liquid 102, which has the consequence that the phase interface 104 between the powder 103 and the liquid 102 also comes to lie at a 20 lower level in the vial 10. Fig. 1 d-4 shows the situation at the end of the test. By monitoring the positions of the liquid surface 106 and the powder/liquid interface 104, the rates of evaporation and solution can be monitored during the test.

Fig. 1e-1 shows the start of a fifth example of a phase behaviour experiment, at which a vial 10 is provided with a first liquid 112. In this phase behaviour experiment, a reservoir 110 25 of a second liquid 113 is provided. This second liquid in a solution having a high concentration of substance X. This second liquid 113 is gradually added to the first liquid 112 in the vial, so that in the course of the experiment, the concentration of substance X in the vial 10 increases. This is shown in figures 1e-2 and 1e-3. In fig. 1e-4 a critical value for the concentration of substance X has been exceeded, and phase layers 115 and 116 are formed. 30 The phase layers 115 and 114 are separated from each other by phase interface 114.

Fig. 2a-d show a selection of possible set-ups of the system and method according to the first option.

Fig. 2a shows two vials 10, in top view. In general, a system according to the invention 35 will have more vials, like four, sixteen, forty-eight, ninety-six or even more. Just for the sake of simplicity, only two vials 10 are shown here. The skilled person will understand that if more vials are present, they will be arranged in a similar manner.

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In the example of fig. 2a, two detectors D are provided. So, in this embodiment, there are as may detectors D as there are vials 10. Each detector D has a field of vision 11. Objects that are present in this field of vision 11 are visible to the detector D. Each detector D has a single vial 10 in its field of vision 11.

5 The vials 10 are at least partly transparent. If they are not fully transparent, they will generally have a “window” of transparent material. It will be clear to the skilled person that in such a case, the vials will be arranged relative to the detector in such a way that the detector can look through the window to see what is happening in the associated vial.

The detectors D are arranged in such a way that they produce image data pertaining to 10 a side view of the vials. Such an image is for example shown in fig. 3a. Within the field of vision 11, one vial 10 is present. The side view clearly shows the phase layers 5,6,7, and 8 and the phase interfaces 4 between them.

Each detector D is provided with an image sensor, that generates image data relating to the side view of the vial 10 in the field of vision 11 of the detector D. In general, the image 15 data will be generated in the form of image data sets. The data in each set can be transformed to form a “picture” of the vial taken at a certain moment in time. Such a picture can be a photo-like image, but as alternative or in addition it can also take the form of a graph, a table, a chart, a parameter value or an other type of representation of data. This applies to all embodiments of the invention. In general, multiple image data sets (multiple 20 “pictures”) are taken of each vial, so that the process -if any- that takes place in the vial during the phase behaviour test can be monitored.

As the vials 10 and the detectors D are arranged in parallel, it is possible to collect image data of all vials 10 simultaneously.

In order to be able to handle all the image data collected by the detectors D, a plurality 25 of data buffers B is present. These data buffers can for example be SDRAM memory cards.

In the example of fig. 2a, each detector is connected to its own data buffer B by means of data connection 12. In each data buffer, image data received from the detector D with which the data buffer B is connected through data connection 12 is stored. In a possible embodiment, the image data is stored in the form of a table, in which every time new data is 30 stored , the oldest data in the table is overwritten by it.

All the data buffers B are connected to an image processor IP by means of data connection 13. In fig. 2a, each data buffer has its own data connection to the image processor, but in practice it could very well be that all data buffers are connected to a serial bus, which in turn is connected to the image processor. The image processor retrieves image 35 data from the data buffers and transforms this image data into a format that allows analysis of the image data in order to be able to obtain test results of the phase behaviour tests that are carried out, such as a photo-like image, but as alternative or in addition it can also take the -9- form of a graph, a table, a chart, a parameter value or an other type of representation of data, or combinations of any of those. The transformed image data is then presented to an image analyser, which does the actual analysis of the images obtained by the detector. The image analyser can be an automated system that comprises image analysis software, but it can also 5 be a human operator that interprets the obtained data.

In this example, a single image processor is provided in the system. It is however also possible that multiple image processors are provided, that process image data in parallel.

By storing the image data in a data buffer B before bringing it to the image processor IP and/or the image analyser IA, the demand on the processing speed of the system is reduced.

10 Many convenient image sensors for use in detectors that are suitable for use in phase behaviour tests, such as mobile phone cameras or webcams, produce a large amount image data per unit of time, resulting in large bit rates that have to be handled by the system. By storing the image data in the data buffer, the image processor IP and/or the image analyser IA can retrieve the image data at their own pace. It is also possible to program the system 15 such that the image data is retrieved sequentially from the data buffers B, so first from the first data buffer, then from the second data buffer and so on. An other practical option would be to have the image processor IP and/or the image analyser IA retrieve only a selection of the image data, for example one data set in every five data sets that are stored in the data buffer for each vial.

20 During the image analysis, the image data is analysed for indications for example creaming, sedimentation, flocculation, coalescence, mixing, de-mixing, solution of one component in the other and/or similar processes. This is done by looking for areas within the vial that have different properties than others. For example, in the analysis one could look for colour differences occurring within the contents of the vial. This is useful in case the different 25 phases have different colours. Phase layers and phase interfaces can then easily be recognised by an operator or by image analysis. By comparing multiple images taken over time of the same vial, the development of the process of for example creaming or sedimentation can be monitored and/or reconstructed. In some cases, particle size and/or droplet size changes can be monitored as well this way.

30 An other option is to look at differences in transparency occurring in the vial. This can be recorded for example by arranging a light source adjacent to the vial, on the opposite side of the detector. If different phases have different transparency, then for example phase layers and their interfaces can be recognised easily. In some cases, particle size and/or droplet size changes can be monitored as well this way. For this techniques, image sensors such as 35 CCD-chips or CMOS-chips can be used, but an other option is to arrange one or more light sources (such as LED’s or optical fibres for example) on one side of the vial and an array of photosensors on the opposite side of the vial. The amount of radiation that a photosensor -10- receives is related to the local transparency of the substance in the vial. Of course, if one wants to detect for example phase layers, the array of light sources and the array of photosensors extend over at least a part of the height of the vial, and preferably over substantially the entire height.

5 If the substance in the vial is opaque, backscatter and/or reflection measurements can be used to identify different phases, phase interfaces, droplet size, gas bubble size and/or particle size.

Other techniques that can be used to identify different phases, their distribution over the vial and/or the size and location of the phases and or the particles, bubbles or droplets that 10 make up one or more of the phases include for example spectroscopy such as RAMAN-analysis.

Fig. 2b shows a second exemplary embodiment. This system is very much like the embodiment of fig. 2a, only this time image data from both detectors is stored in a single data buffer B.

15 Fig. 2c shows a third exemplary embodiment. This system is very much like the embodiment of fig. 2a, only this time each detector D has two vials 10 in its field of vision 11.

Fig. 2d shows a fourth exemplary embodiment. This system is basically the embodiment of fig. 2b combined with the embodiment of fig. 2c.

20 Fig. 3b shows an example of a picture that is produced from an image data set obtained by a detector that has three vials 10 in its field of vision 11. Depending of the size of the field of vision 11 of a detector, any suitable number of vials can be arranged in that field of vision.

In fig. 3b, again reference numerals 5,6,and 7 represent different phases, and reference numeral 4 represents the phase interfaces.

25

Fig. 4 represents a preferred embodiment. In this embodiment, a Field Programmable Gate Array (FPGA) is included in the system. The FPGA is a example of a programmable hardware component or high performance processor, that can be programmed to fulfil certain tasks. In fig. 4. image data is transported from the detectors to the data buffers B via an 30 FPGA. The system can have one or more FPGA’s. The FPGA can be programmed to compare image data and/or subsequent image data sets from an individual vial with one another in order to monitor what is going on in that individual vial. This will usually be done for all vials in the system. Once interesting changes are detected in a certain vial, predetermined actions can be triggered by a control system that controls the system. For example, the time 35 between obtaining two image data sets of that vial can be reduced, or more image data sets per unit of time pertaining to that particular vial can be send to the image processor and/or image analyser.

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Also, the absence of certain changes in a particular vial can be used to trigger actions, for example reducing the number of image data sets obtained per unit of time or processor and/or analysed per unit of time.

Also other actions can be triggered, like start or stop stirring, change the temperature, 5 change the pressure, add a fluid, and so on.

Alternatively or additionally the FPGA’s (or FPGA, if there is only one) can be used to perform calculations on the image data. For example, particle size and/or droplet size of a dispersed phase can be calculated and/or the size of any gas bubbles, and/or the distribution of the particle, bubble and/or droplet size over het height of the vial, the velocity of moving 10 gas bubbles, particles and/or droplets and/or the direction in which they move, the thickness of phase layers, the density of phase layers the location of phase interfaces and so on. Also, the outcome of such calculations can be used in a feedback loop to the control system of the system, triggering certain actions as describes above.

The calculations and/or comparisons can be carried out before or after storage of the 15 data in the data buffer. They can also be carried out at the time certain image data is retrieved by the image processor and/or image analyser. The comparisons and/or calculations can also be done by other components then the FPGA, for example the image analyser or a dedicated data processor.

One or more FPGA’s can be used in combination with all embodiments of fig. 2.

20

Fig. 5 shows a variant of the embodiment of fig. 4. In the embodiment of fig. 5, microprocessors MP are added. Those microprocessors can be used to control the FPGA, to set up the detector or parts thereof and/or to handle incoming commands from for example the image processor and/or the image analyser.

25

Fig. 6 shows an embodiment of the second system according to the invention with which high bit rate demands on the system can be avoided. Components similar to those of the system with the buffer according to the invention and its embodiments work in a similar or the same way, as will be understood by the skilled person. In the embodiment of fig. 6, each 30 of the vials 10 is provided with two detectors. In this example, the primary detector comprises an array of light sources 20. LED’s are suitable to be used as light sources in this application, but also other light sources, such a optical fibre arrangements can be used. On the opposite side of the vial, an array of photosensors 21 is arranged. The photosensors 21 detect the intensity of the light that they receive from the light sources 20. The vials 10 are at least 35 partially transparent, such that the light from the light sources can pass through the vial 10 and be received by the photosensors 21 on the opposite sides. The array of light sources 20 -12- and the array of photosensors 21 are arranged such that they extend along the height of the vial.

With the combination of the array of light sources 20 on the one side of the vial and the array of photosensors 21 on the other side, differences in transparency can be detected, 5 which can be used for determining particle and/or droplet size, detection of different phases, the forming or breaking up of phase layers and so on.

All light sources can be activated simultaneously, or they could be activated sequentially, either one by one or in groups.

In general, a detector of this type, with a combination of an array of light sources and an 10 array of photodetectors, generates image data at a relatively low bit rate.

The secondary detectors 25 each comprise a lens 27 and a CCD-chip or CMOS-chip 26. The secondary detector 25 produces image data at a far higher bit rate as compared to the primary detector 20,21.

Both the primary and the secondary detectors can have a image sensor that is sensitive 15 to visible light, infrared, near-infrared, ultraviolet or other types of radiation. It is not necessary that the image sensor of the primary detector is sensitive to the same kind of radiation as the image sensor of the secondary detector, but it is possible that they are. The combination that is used will depend on the actual use of the system. For the performance of different tests or the testing of different substances, different choices can be made.

20

In a system according to fig. 6, initially just the primary detectors monitor what is taking place in the vials 10. Subsequent image data sets of each individual vial 10 are compared to determine whether changes take place within the vial 10, such as creaming, sedimentation, flocculation, coalescence, mixing, de-mixing, solution of one component in the other, 25 formation of gas or a similar phase behaviour process. Once changes of interest occur in a certain vial 10, the secondary detector 25 associated with that vial is activated. The primary detector 20,21 may then be turned off or left on, whatever is considered the most convenient. By turning the primary detector of, the required bandwidth for data transmission is reduced somewhat, but by leaving it on, the monitoring of changes continues in the same way as 30 before. Once the changes in the particular vial stop taking place or are no longer interesting, the second detector 25 can be switched off again. This point can be determined based on image data from the secondary detector 25 and/or from the primary detector 20,21 in case the latter is left turned on. The changes in image data sets can be monitored for example by using one or more FPGA’s or other types or programmable hardware components or high 35 performance processors, as described in the embodiments of fig. 4 and 5.

The embodiment of fig. 6 can be combined with the embodiments of figures 2, 4 and/or 5. A system combining the embodiments of fig. 4 and fig. 6 is shown in fig. 7.

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In a suitable way of realising the systems according to any of the previously described embodiments, a vial holder is provided. In such a vial holder, the vials are arranged so as to form an array. Suitably, the vial holder comprises a plurality of cavities, each cavity being adapted to at least partially accommodate one or more vials. The cavities are surrounded by 5 a cavity wall, which is provided with an aperture through which the detector can ‘see’ the contents of the associated vial or vials.

The vial holder can be made of heat conductive material, so it can be used to heat or cool the vials and their contents. It can also be made from a thermally insulating material, that helps to reduce undesirable temperature influences.

10 CLAUSES: 1. System for simultaneously performing phase behaviour tests on a plurality of samples, which system comprises: 15 - a plurality of vials, which vials are adapted to contain a sample of a substance on which a phase behaviour test is to be carried out, each of the vials being at least partly transparent, - one or more detectors, each of the detectors comprising an image sensor which is adapted to generate image data pertaining to a side view of one or more associated 20 vials, said image sensor having a field of vision from which it is able to collect image data, wherein the vials and the one or more detectors are arranged relative to each other in such a way that each of the vials is arranged in the field of vision of at least one detector, therewith allowing simultaneous generation of image data relating to said 25 plurality of vials, - a data buffer, which is connected to one or more detectors by means of a data connection, which data buffer is adapted to store image data received from the detector or detectors to which it is connected, - an image processor, which is connectable to the data buffer, which image processor is 30 adapted to retrieve image data from the data buffer and to transform said image data into a format that allows analysis of the image data.

2. System according to clause 1, wherein the system further comprises a programmable hardware component or high 35 performance processor, which is adapted to direct image data from one or more detectors to said data buffer, -14- and wherein the image processor obtains the image data to be analysed via said programmable hardware component or high performance processor.

3. System according to clause 2, 5 Wherein the programmable hardware component or high performance processor is adapted to detect changes in image data received from an individual detector.

4. System according to clause 2 or 3,

Wherein the programmable hardware component or high performance processor is adapted 10 to perform calculations on the image data received from the detector or detectors.

5. System according to clause 3 and/or 4,

Wherein the image processor and/or the programmable hardware component or high performance processor is programmed such that the frequency with which the image 15 processor obtains the image data from the data buffer relating a to individual vial depends on the outcome of the detection of changes and/or the calculations performed by programmable hardware component or high performance processor.

6. System according to any of the preceding clauses, 20 wherein the system further comprises a vial holder for accommodating a plurality of vials, which vial holder is preferably provided with a plurality of cavities, each cavity preferably being adapted to accommodate at least one vial, wherein each cavity comprises a cavity wall which is provided with an aperture that preferably extends over at least a substantial part of the height of said cavity wall, 25 and wherein the image sensor of the associated detector is preferably arranged such that the image data is obtained through said aperture.

7. System according to any of the preceding clauses, wherein the image sensor comprises a CCD-chip or CMOS-chip, which chip is sensitive to 30 visible light, infrared radiation, near-infrared radiation and/or ultraviolet radiation.

8. System according to any of the preceding clauses,

Wherein each detector has only one vial in its field of vision.

35 9. System according to any of the clauses 1-7,

Wherein at least one detector is arranged with respect to a plurality of associated vials such that said plurality of associated vials are simultaneously in the field of vision of said detector.

-15- 10. System for simultaneously performing phase behaviour tests on a plurality of samples, which system comprises: - a plurality of vials, which vials are adapted to contain a sample on which a phase 5 behaviour test is to be carried out, each of the vials being at least partly transparent, - one or more primary detectors, each of the primary detectors comprising an image sensor which is adapted to generate image data pertaining to a side view of one or more associated vials, said image sensor having a field of vision from which it is able to collect image data, 10 wherein the vials and the one or more primary detectors are arranged relative to each other in such a way that each of the vials is arranged in the field of vision of at least one primary detector, therewith allowing simultaneous generation of image data relating to said plurality of vials, said primary detector having a bit rate at which it produces image data, 15 - one or more secondary detectors, each of the secondary detectors comprising an image sensor which is adapted to generate image data pertaining to a side view of one or more associated vials, said image sensor having a field of vision from which it is able to collect image data, wherein the vials and the one or more secondary detectors are arranged relative to 20 each other in such a way that each of the vials is arranged in the field of vision of at least one secondary detector, therewith allowing simultaneous generation of image data relating to said plurality of vials, said secondary detector having a bit rate at which it produces image data, wherein the bit rate of the secondary detector is higher than that of the primary detector, 25 - an image processor, which is connected to one or more detectors, which image processor is adapted to transform said image data into a format that allows analysis of the image data.

11. System according to clause 10, 30 wherein the primary detector comprises an array of light sources and an array of photosensors.

12. System according to clause 10 or 11,

Wherein the secondary detector comprises a CCD-chip or CMOS-chip, which chip is sensitive 35 to visible light, infrared radiation, near-infrared radiation and/or ultraviolet radiation.

13. System according to any of the clauses 10-12 , -16- wherein the system further comprises a data buffer which is connected to one or more detectors by means of a data connection, which data buffer is adapted to store image data received from the detector or detectors to which it is connected, and wherein the image processor, which is connectable to the data buffer, is adapted to retrieve image data from the 5 data buffer.

14. System according to any of the preceding clauses ,

Wherein the vials and the detectors have a fixed position relative to each other.

10 15. Method for simultaneously performing phase behaviour tests on a plurality of samples,

Which method comprises the following steps: - providing a plurality of at least partly transparent vials - arranging a sample of a substance to be tested in each of those vials, - providing one or more detectors, each having a field of vision from which it is able to 15 collect image data, and arranging said one or more detectors in such a way with respect to the vials that each of the vials is arranged in the field of vision of at least one of the detectors, - simultaneously generating image data from each of the plurality of vials using the one or more detectors, which image data pertains to a side view of the vials, 20 - transferring the image data from each detector to a data buffer, - storing the image data in said data buffer, - retrieving image data from said data buffer, - transforming the image data into a format that allows analysis of the image data.

25 16. Method according to clause 15,

Wherein a selection of the image data is retrieved from the data buffer.

17. Method according to clause 15 and/or 16,

Wherein the method is carried out during a period of time, during which period of time multiple 30 sets of image data are obtained from each vial, allowing the monitoring of changes in phase behaviour, the position of phases in the vial and/or the phase distribution taking place in each sample during said time period.

18. Method according to clause 16, 35 Wherein the changes in subsequent image data from an individual vial are monitored, and the occurrence or absence of such changes are used for control purposes.

-17- 19. Method for simultaneously performing phase behaviour tests on a plurality of samples, Which method comprises the following steps: - providing a plurality of at least partly transparent vials - arranging a sample of a substance to be tested in each of those vials, 5 - providing one or more primary detectors, each having a field of vision from which it is able to collect image data, and arranging said one or more primary detectors in such a way with respect to the vials that each of the vials is arranged in the field of vision of at least one of the primary detectors, - providing one or more secondary detectors, each having a field of vision from which it is 10 able to collect image data, and arranging said one or more secondary detectors in such a way with respect to the vials that each of the vials is arranged in the field of vision of at least one of the secondary detectors, - simultaneously generating image data from each of the plurality of vials using the one or more primary detectors, which image data pertains to a side view of the vials, 15 - monitoring the image data obtained from each individual vial, and detecting changes in said image data, - upon the meeting of a predetermined condition with respect to change taking place in said individual vial, activating the secondary detector associated with said vial, - transferring the image data to an image processor, 20 - transforming the image data into a format that allows analysis of the image data.

20. Method according to clause 19,

Wherein the method further comprises the following steps: - transferring the image data from each detector to a data buffer, 25 - storing the image data in said data buffer, - retrieving image data from said data buffer.

Claims

5. System as claimed in claim 3 and / or 4, wherein the image processor and / or the programmable hardware component or high performance processor is programmed such that the frequency with which the image processor obtains the image data from the data buffer with respect to an individual test tube depends on it. result of the detection of changes and / or calculations performed by the programmable hardware component or high performance processor. 6. System as claimed in any of the foregoing claims, wherein the system comprises further test tube holder for accommodating a plurality of test tubes, which test tube holder is preferably provided with a plurality of cavities, wherein each cavity is preferably adapted to receive at least one test tube, in which each cavity has a cavity wall which is provided with an opening which preferably extends over at least a substantial part of the height of the cavity wall, and in which the image sensor of the associated detector is preferably arranged such that the image data is obtained via this opening. A system according to any one of the preceding claims, wherein the image sensor comprises a CCD chip or a CMOS chip, which chip is sensitive to visible light, infrared radiation, near infrared radiation and / or ultraviolet radiation. 20

A system according to any one of the preceding claims, wherein each detector has only one test tube in its field of vision.

9. System as claimed in any of the claims 1-7, wherein at least one detector is arranged with respect to a plurality of associated test tubes such that said plurality of associated test tubes are simultaneously in the field of view of this detector.

10. A system for simultaneously performing phase behavioral tests on a plurality of samples, which system comprises: 30. a plurality of test tubes, which test tubes are adapted to contain a sample of a substance on which a phase behavior test can be performed, wherein each test tube is at least partially transparent one or more primary detectors, each of the primary detectors comprising an image sensor adapted to generate image data with respect to a side view of one or more associated test tubes, the image sensor having a field of view from which the image data can be collected, the test tubes and the one or more primary detectors are arranged relative to each other such that each of the test tubes is arranged in the field of view of at least one primary detector, thereby enabling the simultaneous generation of image data relating to a plurality of test tubes, the primary detector has a bit rate at which it be produces one or more secondary detectors, each of the secondary detectors comprising an image sensor adapted to generate image data with respect to a side view of one or more associated test tubes, the image sensor having a field of view from which the image data can be collected wherein the test tubes and the one or more secondary detectors 10 are arranged relative to each other such that each of the test tubes is placed in the field of view of at least one secondary detector, thereby enabling simultaneous generation of image data with respect to a plurality of test tubes, the secondary detector has a bit rate at which it produces image data, wherein the bit rate of the secondary detector is higher than that of the primary detector, an image processor connected to one or more detectors, which image processor is arranged to convert the image data into a form that a allows analysis of the image data.

The system of claim 10, wherein the primary detector comprises a series of light sources and a series of photosensors.

12. System as claimed in claim 10 or 11, wherein the secondary detector comprises a CCD chip or CMOS chip, which chip is sensitive to visible light, infrared radiation, near infrared radiation and / or ultraviolet radiation.

13. System as claimed in any of the claims 10-12, wherein the system further comprises a data buffer which is connected to one or more detectors by means of data connection, which data buffer is adapted to store image data received from the detector or detectors to which it is connected, and wherein the image processor, which is connected to the data buffer, is arranged to retrieve image data from the data buffer.

14. System as claimed in any of the foregoing claims, wherein the test tubes and detectors have a fixed position with respect to each other. -21 -

15. A method for simultaneously performing phase behavioral tests on a plurality of samples, the method comprising the steps of: - providing a plurality of at least partially transparent test tubes, - applying a sample of a substance to be tested in each of these test tubes, 5. providing one or more detectors, each having a field of view from which it is possible to collect image data, and arranging these one or more detectors with respect to the test tubes such that each of the test tubes in the field of view of at least one of the detectors are placed, - simultaneous generation of image data from each of the multiple test tubes using the one or more detectors, which image data relate to a side view of the test tubes, - transferring the image data from each detector to a data buffer, - storing the image data in this data buffer, - retrieving the image data from from this data buffer, 15. converting the image data into a form that allows analysis of the image data.

The method of claim 15, wherein a selection of the image data is retrieved from the data buffer. 20

A method according to claim 15 and / or 16, wherein the method is performed for a period of time, during which period of time several sets of image data are obtained from each test tube, making it possible to change phase behavior, the positions of phases in the test tube and / or or follow the phase distribution that takes place in each sample during this time period.

The method of claim 16, wherein the changes to subsequent image data from an individual test tube are tracked, and the occurrence or absence of such changes is used by control purposes. 30

19. Method for simultaneously performing phase behavioral tests on a plurality of samples, the method comprising the steps of: - providing a plurality of at least partially transparent test tubes, - applying a sample of a substance to be tested in each of these test tubes, providing one or more primary detectors, each having a field of view from which it is possible to collect image data, and arranging these one or more primary detectors with respect to the test tubes, such that each of the test tubes in the field of view of at least one of the primary detectors is placed, - providing one or more secondary detectors, each having a field of view from which it is possible to collect image data, and arranging one or more secondary detectors with respect to the test tubes such that each of the test tubes is placed in the field of view of at least one of the secondary detectors, - simultaneously generating image data from each of the plurality of test tubes using one or more primary detectors, which image data relate to a side view of the test tubes, - tracking the image data obtained from each individual test tube, and detecting of changes in this image data, - upon reaching a predetermined situation with regard to change occurring in this individual test tube, activating the secondary test tube 15 associated with this test tube, - transferring image data to an image processor, - converting image data into a form that allows analysis of the image data.

The method of claim 19, wherein the method further comprises the steps of: - transferring image data from each detector to a data buffer, - storing the image data in this data buffer, - retrieving image data from this data buffer. 25