AUTOMATIC MULTIPLE CELL SCREENING MEANS

Abstract: Apparatus and a method for measuring and comparing the optical properties of liquids, particularly liquids containing a solid, in which the liquids are held in a series of containers (2) held in a holding means (3) in a carousel (1); the carousel is rotated so the containers sequentially pass through a beam of light from a laser (9) with the light passing through each liquid preferably via a quarter wave plate (12) and then a beam splitter (14) which splits the light into two orthogonally polarised beams of light which are passed to a photodetector (15, 16). By measring and comparing the properties of each beam of light the properties of the liquid can be measured. The method is particularly useful for continuously measuring clathrate formation in a clathrate forming system in the container; the properties which can be measured are the transmission, birefringence and viscosity, by having a magnetic stirrer (22) and detecting the rate of stirring changes in the viscosity can be measured.

Description: Automatic Multiple Cell screening Means The present invention relates to apparatus and a method for measuring characteristics or properties of solids in liquids, more particularly, it relates to apparatus and a method which can be used for determining simultaneously different characteristics or properties of solids in liquids, using the optical properties of the solids and liquids. The detection and measurement of characteristics of solids in liquids, e.g. suspended, precipitated, crystallised, etc. is used with micro-organisms and other biological material, wax precipitated from petroleum products, formation of gaseous hydrates, etc. Existing methods which have been used pass a beam of light through the liquid containing the solid and, depending on e.g. the intensity of resultant light, fluorescence of reflected light, wavelength, etc. the properties or nature of the solid in the liquid can be determined. Methods are described in US Patents 3,348,614; 4,597,779; 4,856,593; 5,076,364; 5,244,878; 5,331,105; 5,432,292; 5,434,323; 5,460,728. We have now invented an improved method and apparatus which enables a plurality of properties to be measured. According to the invention there is provided apparatus for determining the optical properties of liquids, which apparatus comprises a holding means capable of holding a container containing the liquid, a light source adapted to pass light through a container in the holding means, a beam splitter able to split light passing through the container into two beams of different polarisation and two detectors able to detect and measure the properties of each beam of light emerging from the beam splitter. Preferably there are a plurality of holding means allowing a plurality of containers to be held in the apparatus and the containers can be passed sequentially through the light emitted by the light source. Preferably there is an agitating means whereby the liquid in the containers can be agitated, for example, by rocking or by means of a magnetic stirrer acting in the containers. The beam splitter will preferably split the beam into two orthogonal polarised light beams. A preferred arrangement is for the holding means holding the containers to be held in a carousel or similar circular device and the holding means rotated by means of a motor, allowing the containers to pass sequentially through the light from the light source. Preferably each position of the container has an identifier so that it can be automatically identified. The containers are conveniently tubular with the light passing along their vertical axis from above, with the beam splitter positioned below the container. Preferably the light is coherent light produced by a laser, the wavelength of the light is not critical and commercially available red lasers are suitable. The detectors can be any detector capable of measuring the requisite property of the emitted light, for example, the intensity of the light, e.g. by a photo detector. " Optionally there is positioned a quarter-wave plate between the light source and the holding means so that light passes through the quarter wave plate before passing through a container in the holding means. The quarter-wave plate is preferably positioned with its fast and slow axis at 45 degrees with respect to the polarising plane of the incident light. This forms a polariscope with Sinamon arrangement, which is of the highest sensitivity to the low birefringence measurement condition. The apparatus can be mounted inside an environmentally controlled chamber so that the temperature, atmosphere, pressure, etc. can be controlled. The output from each of the detectors can be passed to a computer so that calculations and manipulations can be carried out on this output to produce a result in the desired form. The invention also provides a method of determining the optical properties of a liquid, which method comprises passing a beam of light through the liquid then then passing the light to a beam splitter which splits the beam to two beams of orthogonal polarised light, passing these two beams to photo detectors which measure properties of the light and using the output from these photo detectors to determine the required properties. In the use of the apparatus of the invention, a liquid containing a solid is placed in a container positioned in the holding means, the light source turned on so that light passes through the liquid to the beam splitter and then the two beams pass to the photo detector. Properties of the light which can be measured and which are useful include the intensity of the light. The sum of the intensity of the two polarised beams of light is a measure of the amount of adsorption of the light and hence of the characteristics of the solid material in the liquid. The ratio of the intensities of the light in the two different planes of polarisation is a measure of the anisotropy of the solid material. For example, if the solid is in the form of anisotropic crystals or optically active material, the ratio of the intensities will be a measure of this anisotropy or optical activity. Three parameters which can be measured are transmission, birefringence and viscosity (from agitation stirring data). Scattering of light reduces transparency in the nucleation process when small particles form and the continuous recording of transparency of the system therefore will contain kinetic information on nucleation and crystal growth. Birefringence is the difference between the two principal refractive indices in the plane perpendicular to the propagation direction of the light path, it is a measure of optical anisotropy and has been widely used in the area of materials and crystal studies. Generally speaking, isotropic liquid and cubic crystals like hydrates should have zero birefringence, unless these crystals are somehow deformed, imperfect, or mixed up with non - cubic crystal such as ice. It is also possible for the measured birefringence being non zero, when there are primitive clusters with certain order in their structure which leads to be optical anisotropy. In addition, polymers in dilute solution will not be birefringent when they are in the state of random coils. This conformation however, is liable to be transformed into anisotropic conformation when the polymers are sheared due to flow, or contraction/expansion of the system caused by crystallisation. It is useful to investigate if there is any anisotropic structure formed for example during hydrate formation via the measurement of birefringence, because it would be helpful in the understanding of hydrate formation and inhibition mechanisms. The invention is particularly useful in comparing the properties of different liquid compositions in which case different liquids are placed in a plurality of containers which are sequentially passed through the light from the light source; it is then possible to obtain a comparison of their characteristics or properties from a calculating means or computer connected to the photo detectors. This enables the characteristics or properties to be compared under substantially similar or identical conditions and, by having the equipment in an environmentally controlled chamber, these conditions can be varied. The invention is particularly useful in comparing the effect of different chemicals, such as inhibitors, on the rate of formation, particle or crystal size, density, etc. of solids which can be deposited from or otherwise separate from a liquid, e.g. in the deposition of wax from petroleum products or on the formation or suspension of clathrates or hydrocarbon hydrates. The inhibition of clathrate hydrate formation in pipelines is an issue of important industrial significance. Extensive investigations have been carried out in order to search for better inhibitors. The effect of an inhibitor is usually assessed according to how long it delays the onset of the crystallisation and to what extent does it reduce the crystallisation rate. Tens of polymer species and hundreds of small molecules have already been reported of certain inhibiting effects. There are however, still a variety of possibilities for better inhibitors to be achieved by syntheses of new compounds, modifications of small or macro molecules which are already available or by formation of inhibiting complexities of different types from two or more potential inhibitors. The efficiency of this development, however, relies largely on the knowledge of the inhibiting mechanisms. Due to the schematic feature of nucleation and the complexity of the inhibition system, the inhibiting mechanism is still far from clear. The comparison is, however, still not an easy task for at least three reasons. Firstly, the results are scattered widely due to the schematic nucleation feature and an indecisive conclusion is likely unless perhaps enormous repetition of the experiments could be done. The second reason is that comparisons can not be made based on available results, because data is from different laboratories with a different experiment set-ups. Finally, the reliability of a comparison depends both on how big the difference is between the effects of two inhibitors and how small the difference is between the conditions of the two experiments from which the results were obtained respectively. The smaller the difference in inhibiting effects the more accurate the experiment condition is needed. The present invention overcomes these difficulties. In studying clathrate formation the three independent parameters referred to above are measured in a continuous spectrum which records the whole hydrate formation process (also applied to the melting process). The geometric position of specimen tubes can be identical from the view of time scales longer than 30 seconds and all the three parameters are measured automatically and simultaneously so that they are objective and have good comparability. When a magnetic stirrer is used to stir the contents of the container, a comparison of the rate of stirring gives a measure of the comparative viscosity of the contents of each of the containers. Viscosity changes during hydrate formation can be measured continuously by change of the measured stirring rate of fleas in liquid samples and/or viscosity changes will also be monitored by means of transparency which varies due to the change in the conformation of the vortex in each sample tube. In the preferred arrangement the containers are held in a carousel and the holding means rotated by means of a motor, allowing the containers to pass through the light from the light source. As the position of each container has an identifier it can be automatically identified. The containers are tubular with the light passing along their vertical axis, with the beam splitter positioned below the container. The light passing through the tubular containers is passed to the photo detectors and light intensity versus time curve from each of the sample tubes is obtained by cutting the whole continuous curve into segments according to a time reference created by a single spike from a third photocell. The spike is due to deliberate exposure of the detector to the laser reflected from the polished surface of a brass prism reflector seating on the top of the upper tube holder disk at a gap between two specimen tubes. When it is carried by the cell holder to the position where it meets the incident beam, the incident beam is reflected to the photo detector. The spike thus stands as the time reference at the start of every new revolution. The start and end of a scan on a sample, on the other hand, are marked by the total extinction of the laser energy. Every tube is sampled once in one revolution. The average extinction of each sample over the period of one scan is calculated as the mean value of the light intensity curve of the sample within the scan. The time and temperature dependence of the average extinction for each sample can be obtained with FAMOS software by regrouping and treating the chopped segment of I-t curve from the whole continuous raw data. The sum of the average extinction from the dark and bright fields with or without Sinamon arrangement is taken as the extinction of the sample solely due to optically isotropic transparency. The birefringence term in the expressions of the polarised light intensity from both the bright and dark fields are of opposite sign. The time and temperature dependence of this ratio reveals any change in optic anisotropy during the formation and decomposition process of the clathrate hydrates. The stirrer spinning rate is obtained by Fourier Transform of the chopped light intensity versus time curve of the sample within one scan. The Y position of the two pronounced peaks in the Fast Fourier Transform (FFT) spectrum corresponds to the frequencies of the stirring rate and the beam blocking rate by the stirrer. The later is actually the double frequency of the former, because the stirrer normally hits the beam twice in one spin. The dramatic drop in the magnitudes of the above two peaks as a function of time and temperature is used to mark the stirrer stop point, while the shift of these peak positions indicates the change in viscosity of the sample. The invention will now be described with reference to the accompanying drawings in which Fig. 1 is a side view of the apparatus according to the invention; and Fig. 2 is a plan view and Figs. 3, 4, 5 and 6 show results obtained. A carousel (1) contains twelve tubular containers (2) mounted on holding means (3) on the carousel. The carousel (1) is rotated about shaft (4) by means of an electric motor (not shown). The apparatus is mounted within an environmentally controlled chamber (5) with a transparent top (6). There is a gas inlet (7) in the chamber (5) to enable the nature and pressure of the atmosphere in the chamber (5) to be controlled. There are thermocouples (8) to monitor the temperature. There is a polarised laser light source (9) which emits light through a beam attenuator (1 1) and quarter wave plate (12) through the container (2). The light which passes through the container (2) passes through filter (10) to polarising beam splitter (14) where it is split into two orthogonally polarised light beams Is and Ip which go to photocells (15) and (16). The containers are sealed by means of lid (17) and 'O' ring (23). There is a prism (18) positioned on the carousel which can reflect incident light to photocell (19) through filter (20) to identify each revolution of the carousel. There is a magnetic stirrer (22) in each container and the rate of stirring can be measured by the cutting of the beam by the stirrer. In use, a sample of different liquids is placed in each container (2) and the light turned on. The light passes through the liquid (21) in each container (2) to the beam splitter (14) to the photocells (15) and (16). The output from these photocells are fed into a computer. As each of the lobes of magnetic stirrer (22) crosses the beam it is recorded and so the speed of rotation of the stirrer noted. The carousel (1) rotates at 0.5 rpm so each container (2) passes through the beam and the output from the photocells recorded. In an example of the apparatus of the invention, an eight seat sample holder is a typical example. The specimen tube is 13/12 mm diameter, 50 mm long from BDH. The magnetic stirrer bar is 3 mm diameter and 10 mm long from Nalgene Brand Products. The stirrer machine has a power of 20 w and adjustable stirring rate up to 1 100 rpm. The driving motor to the central shaft is a synchronous motor with a fixed speed of 0.5 rpm. The glass jar is 120 mm inner diameter and 120 mm high. A 3 mw, 670 nm continuous wave diode laser is used as the light source (RS stock no. 194 026). The spot size of the beam is so adjusted that is focuses on the stirring plane of the stirrers. The photocells are all 5 mm 2 photodiodes with amplifier (RS stock no. 308-067). Two of the photocells are integrated into a devised holder together with the polarising beam splitter and the optical filter. The polarising beam splitter is a 12.7 mm 1 cubic for the central wave length of 670 nm. Its transmission of 95% from the p-polarised wave and 99.9% for the s-polarised (Ealing Cat. No. 43-7194/59). The central wave length of the filter is also 670 nm with a band width of 10.8 nm and peak transmission 50% (Ealing 35-4027). The third photocell for the revolution mark prism is integrated with another optical filter of the same type and mounted at the up-left hand corner of the glass jar. In the optimal condition the laser beam scans across the tube along a circular trace outside the circle formed by the centres of the specimen tubes. The gap between the circles is about half of the tube diameter. This is to ensure that the stirrers cut the laser beam with both of their arms when they spin horizontally. To make the stirrers spin in the horizontal plane, a symmetric magnetic field is needed. This can be done by offsetting the glass jar so that the specimen tube under scanning is at the centre of the magnet field. As a result, the motion of the stirrers inside the tubes changes periodically because they experience different magnet force during one revolution. After coming out of the central magnetic field, the stirrers may gradually spin in a vertical plane. This is also beneficial however, because a better agitation can be achieved. Three K-type thermocouples were uniformly mounted inside the jar, the average value of them used as the measured temperature of the samples. The gas temperature is controlled by purge in continuous gas flow from the bottom. The flow temperature is maintained by a heater through which the gas nitrogen passes. The gas nitrogen is generated from the evaporation of the liquid nitrogen stored in a 50 litre Cryo Lab dewer. By adjusting the input voltage to the heater according to a fed back single form a N-type thermocouple in the glass jar, the gas is heated to an appropriate temperature before entering into the jar. The tube holder is made of good thermoconductive materials which help unify the temperature among the sample tubes. The rotation of the cage inside the jar also helps the tubes being exposed to the same temperature environment and experienced the same thermal history. A Windmill interface and software is used to collect data. For the cage rotation rate of 0.5 rpm and stirring rate of 500 rpm, the premier data acquisition rate of the computer is once a micro second for the light intensities measurement of the all three channels, the parallel, perpendicular and the marker. The secondary data acquisition rate is selected for the three temperature detecting sensors, which is 50 times slower than that of the premier rate. When used to measure the effect of inhibitors on clathrate formation, the same liquid, e.g. a THF/water mixture is placed in each container and the chamber cooled to 0°C. Different inhibitors are added to each container and the light turned on and the carousel operated. It is then possible to automatically compare the nature and rate of clathrate formation in each of the cells under the same conditions over a period of time and thus compare the effect of the inhibitors. Results are shown graphically in Figs. 3 and 4 in which fig. 3 is a typical intensity/time curve for one revolution and shows a series of twelve peaks for twelve sample tubes between the large peaks at the start of each Fig. 4 shows a single peak of fig. 3 in detail with the many small peaks being due to blockage of the incident beam by the stirrer. Fig. 5 is a plot of the stirring rate, birefringence and transmission against time for one sample and shows a clear discontinuity at the onset of clathrate formation in all these parameters it can be seen from the curve 1 , which the sum of the intensities of the light from the two beams produced by the beam splitter, (I s +I p) that there is a sharp drop at the onset of crystallisation, the curve 2 which is a measure of the ratio of IJ t> I- p. shows an increase at the onset of crystallisation due to the appearance of anisotropic crystals and curve 3 shows the sharp drop in stirring rate. Fig. 6 shows a plot for a series of samples containing different amounts of PVP with sample 1 1 being water. As can be seen there are different points of discontinuity for the plots obtained, showing the different times for clathrate formation, thus showing the relative effects of the different amounts of the PVP inhibitor.

Claims: Claims 1. Apparatus for determining the optical properties of liquids, which apparatus comprises a holding means capable of holding a container containing the liquid, a light source adapted to pass light through a container in the holding means, a beam splitter able to split light passing through the container into two beams of different polarisation and two detectors able to detect and measure the properties of each beam of light emerging from the beam splitter. 2. Apparatus as claimed in claim 1 in which there are a plurality of holding means allowing a plurality of containers to be held in the apparatus and the containers can be passed sequentially through the light emitted by the light source. 3. Apparatus as claimed in claim 2 in which the holding means holding the containers are held in a carousel and the holding means rotated by means of a motor, allowing the containers to pass sequentially through the light from the light source. 4. Apparatus as claimed in claim 3 in which each position of the container has an identifier so that it can be automatically identified. 5. Apparatus as claimed in any one of the preceding claims in which the containers are tubular and the light source is positioned above the holding means so that the light will pass down along the vertical axis of a container held in the holding means from above and the beam splitter is positioned below the container. 6. Apparatus as claimed in any one of claims 1 to 5 in which the beam splitter can split a beam into two orthogonal polarised light beams. 7. Apparatus as claimed in any of the preceding claims in which each position of a container has an identifier so that it can be automatically identified 8. Apparatus as claimed in any of the preceding claims in which the detector is a photo detector which can measure the intensity of light. 9. Apparatus as claimed in any of the preceding claims in which there is a quarter-wave plate positioned between the light source and the holding means so that light passes through the quarter wave plate before passing through a container in the holding means. 10. Apparatus as claimed in claim 10 in which the quarter-wave plate is positioned with its fast and slow axis at 45 degrees with respect to the polarising plane of the incident light. 11. Apparatus as claimed in any one of the preceding claims mounted inside an environmentally controlled chamber. 12. A method of determining the optical properties of a liquid, which method comprises passing a beam of light through the liquid then passing the light to a beam splitter which splits the beam to two beams of orthogonal polarised light, passing these two beams to photo detectors which measure properties of the light and using the output from these photo detectors to determine the required properties. 13. A method as claimed in claim 12 in which the properties measured are transmission, birefringence and viscosity. 14. Apparatus for determining the optical properties of liquids as claimed in claim 1 as hereinbefore described with reference to figs. 1 and 2 of the drawings.

Inventors: KOH CAROLYN ANN, SAVIDGE JEFFREY, ZHANG WU, KOH, CAROLYN, ANN, SAVIDGE, JEFFREY, ZHANG, WU
Applicants: KING S COLLEGE LONDON, KOH CAROLYN ANN, SAVIDGE JEFFREY, ZHANG WU, KINGS COLLEGE LONDON, KOH, CAROLYN, ANN, SAVIDGE, JEFFREY, ZHANG, WU
Application year: 1997
Main classification: G01N21
IPC codes: G01N21