SENSOR

Abstract: A sensor for measuring absorption of electromagnetic radiation (4) by a sample (3) comprising a heat conducting solid element (1) which is transparent to said radiation and is in thermal contact with a thermal detector (2) which measures the increase in temperature induced in the sample (3) by absorption of radiation (4).

Description: "Sensor" This invention concerns a novel sensor for determination of absorption of electromagnetic radiation by an analyte and a method of determination using such a sensor. Absorption of electromagnetic radiation, typically visible light, is commonly used for the detection and/or quantification of chemical substances or acquisition of information concerning such substances. In general, photometric methods used previously have relied on measuring the transmission of the incident radiation and relating this to a standard transmission value. However, such methods are sensitive to radiation scattering and are often unsuitable for analysis of particulate samples. Recently, however, methods have been proposed which measure absorption directly by determining the temperature increase in the analyte caused by absorption of the incident radiation, and thus avoid problems caused by scattering. Tanato et al (J. App. Phys. 63(6) p.185, 1988) have described a system of photothermal spectroscopy for thin solid films wherein the thin sample is mounted on a transparent temperature sensor and irradiated with pulsed light to measure increases in sample temperature caused by absorption. However, due to the incomplete transparency of the thermal sensor, this itself becomes heated. This aberration is worsened where the sample scatters the incident light and thus both light scattering and light absorption will increase the signal thereby giving an anomalous result. Further, the transparent sensor comprises a sandwich of a thermosensitive material between electrode films. The latter have to be extremely thin to reduce absorption and are consequently very susceptible to both mechanical and chemical degradation. Additionally, the sample is in contact with one of the electrodes whereas it is important to isolate the sample from the electronic circuitry. In some cases, the sample can act as an antenna and pick up disturbances. USP 3948345 describes a photoacoustic method of spectroscopy wherein a gas contained in a resonant container and surrounding the analyte to be investigated is irradiated with pulsed light. The absorption of this light by the analyte and the resulting increase in temperature creates a pulsed elastic expansion, i.e. elastic waves, in the gas which can be detected by a conventional acoustic detector such as microphone. LISP 4303343 using the same principle optimises the relationship between the pulse-frequency, the wavelength of the incident light and other parameters. European Patent 49918 typifies a development of the technique in which absorption of pulsed light by the analyte sample produces pulsed expansion and contraction of a solid element which is transformed into an electrical signal by means of a piezoelectric transducer attached to the solid element. However, such photoacoustic methods are extremely sensitive to local vibrations and have proved difficult to use in some cases. We have now found that by irradiating the sample through a solid element which is transparent to the incident radiation, and thus not heated by it, and yet is highly conductive to heat, and by providing a thermal detector on the solid element close to the sample, it is possible to detect directly increases in temperature of the sample caused by irradiation. According to the present invention therefore we provide a sensor for the detection or quantification of absorption of electromagnetic radiation by a adiu e wπerein the increase of temperature induced in the sample by the radiation produces a signal proportional to said temperature increase, characterised in that the sensor comprises a heat conducting solid element which is transparent to said electro¬ magnetic radiation and which has a first surface for contacting with said sample, a radiation input surface and a radiation path between said surfaces, thermooptic or thermoelectric thermal detector means being provided in thermal contact with said solid element close to said first surface to receive conducted heat therefrom without obstructing said radiation path. It will be appreciated that by placing the thermal detector substantially outside the path of the incident radiation, the effect of radiation scattering by the sample is minimised. In general, the sensor will be provided with means for irradiating the sample through the solid element. It is particularly advantageous to irradiate with radiation which is modulated with respect to amplitude and/or wavelength since this enables background errors such as overall temperature variations largely to be eliminated. The radiation may be ultraviolet, visible or infrared light. Amplitude modulation or pulsing of the incident radiation can conveniently be achieved by a conventional mechanical light chopper placed in the collimated light path. Variation of the wavelength of the incident light, e.g. between an absorption maximum and a minimum, may, for. example, be effected by a laser diode. In general, the modulation frequency should be low e.g. below 50 Hz. The frequency of signal amplification or other periodic means of electronic sampling can be synchronised or locked onto the modulation frequency of the incident radiation so that extraneous temoerature variations occurring between the pulses are not amplified. Apparatus for effecting such modulation and sampling are described in USP 3948345. Furthermore, the pulse frequency can be related to the rate of conduction of heat from the sample to the sensor. Thus, the amplitude of the signals produced by the temperature fluctuations depends in part on the transfer of heat from irradiated sections of the sample at a given distance from the surface of the transparent solid element. Heat generated at points deeper into the sample is not transferred to the sensor in the time between incidence of the radiation and sampling of the signal from the thermal detector. The maximum depth within the sample from which heat contributes to the signal is termed the 'thermal diffusion length' and defines the volume of the sample which is analysed. This definition of the volume makes quantification of an absorbing substance possible. Incident light is conveniently led to the sensor by means of an optical fibre system. The light source may be a laser or a strong lamp. In general, it should be possible to produce incident radiation in the wavelength range 250 nm to 2500 nm. The thermal detector may, for example, be a thermoelectric device such as thermistor or thermo¬ couple or a thermooptical device such as a temperature responsive laser. The solid heat conductive element may conven¬ iently be made of diamond, which has a heat conductance six times that of copper, or sapphire or quartz, all of which are substantially completely transparent to ultraviolet, visible and infrared light. The solid element is conveniently in the form of a block with two opposed ends and at least one side onto which a thermal detector can be mounted. The sample can then be mounted on or thermally contacted with one of the ends (the "sampling end") while the incident radiation enters the block through the opposite end, the path between the radiation source and the sample thus being unobstructed. It may be advantageous for the sampling end of the block to be rounded to some extent, since this will increase the surface area of the block which will contact a given volume of sample material. The sampling end of the block may if desired be given a thin protective coating, e.g. of a plastics material such as an epoxy resin. The thickness of the coating should be such that there is no undue reduction in thermal contact between the sample and the block (the use of a rounded sampling end as described above may assist in offsetting any such reduction) . The use of protective films of plastics materials such as polycarbonates, polyacrylates polyamides, polyesters, polyalkylenes and polyhaloalkylenes especially if extended to protect the thermal detector, may be particularly advantageous where hazadous (e.g. infectious or toxic) or chemically highly reactive samples are to be investigated. The films may advantageously be designed to be disposable, especially where infectious or toxic samples are to be encountered. The solid heat conductive element may if desired comprise more than one component. Thus, for example, a block may have a thin disc of similar material transparently adhered to one face so that one side of the disc forms the sampling end of the element. The thermal detector in such arrangements may be attached to the block or the underside of the disc as appropriate, and will be particularly well protected against contamination by sample material. In most applications, however, the thermal detector is advantageously mounted on a surface of the heat conducting solid element which extends parallel to the radiation path. Substantially total internal reflection of the incident radiation at the said parallel surface should then prevent the radiation from reaching the detector. Such internal reflection may be enhanced by attaching the thermal detector to the solid element using an adhesive having a smaller index of refraction than the material of the solid element. Since materials such as sapphire and diamond have a high index of refraction, a wide range of adhesives may be used, including epoxy adhesives, cyanoacrylate adhesives and polyester adhesives. The adhesive may additionally be used to coat the remaining sides of the solid element to minimise egress of light therefrom. Particularly suitable adhesives include electrically conductive glues such as metal epoxy glues, for example a silver epoxy such as Epo-tek H 20 E (manufactured by Epoxy Technology Inc., Mass., U.S.A) , since these ensure maximum light retention while also having good thermal and electrical conductivity. Alternatively, the surface of the transparent solid element may be coated with a reflective layer, e.g. a thin layer of aluminium or silver, before attachment of the thermal detector, such treatment being particularly suited to measurements in the ultraviolet and infrared regions. Where a thermistor is employed as the thermal detector this may, when the scale of the apparatus permits, be formed by thick film technology, i.e. by printing a paste of thermistor material onto the solid element after any necessary pretreatment to ensure maximum internal reflection and then sintering the paste at high temperature. The distance between the sample and the thermal detector is preferably as small as possible, in order to minimise the time for conduction of heat from the sample to the detector and thereby achieve maximum sensitivity. In general, the specific conductivity of the solid element will be many times that of the sample. Typically, the distance of the thermal detector from the sampling end of the element will be of a similar order of magnitude to the dimensions of the sampling end. Thus, for example, the thermal detector might be mounted about 1 mm from a sampling end which itself is about 1mm across. Alternatively the surface of the sampling end may extend further along the axis passing through the detector to provide a larger, essentially oblong area in contact with the sample. Where the sample absorbs the incident radiation strongly, the latter will readily be absorbed within the thermal diffusion length and produce a strong signal. Where absorption is low, only a part of the incident light may be absorbed within the thermal diffusion length. It will be appreciated that in general, the thickness of the sample should exceed the thermal diffusion length and is preferably at least twice that length. Sensors according to the invention may, if desired, be very small. The thermal detector can readily be made of the same size or smaller than the heat conducting solid element. It is particularly convenient to mount the solid element on the end of an optical fibre; the signal from the thermal detector can be conducted by electrical wires or an optical fibre, conveniently mounted parallel to the optical fibre for the incident radiation. Sensors so arranged can readily be used to detect or quantify samples in a wide range of situations, for example not only in in vitro experiments but also jj vivo. Thus, for example, such a sensor may be inserted into a blood vessel for continuous measurement of haemoglobin content. It is particularly useful to be able to immerse such a sensor in a liquid sample to examine the analyte at different depths, in particular at points distant from the surface; for example erythrocytes will absorb oxygen from the atmosphere when near to the surface of a liquid sample containing them and thus may alter their absorption spectrum. In certain applications it may be necessary to shield the sensor from thermal influences or chemical corrosion. One or more protective layers, e.g. of any appropriate polymer material, may, for example, be applied over the whole sensor, excluding the surface in contact with the sample, in order to achieve this end. Shielding against electrical influences or disturbances may also be desirable in particular applications and may, for example, be effected by surrounding the sensor (again excluding the surface in contact with the sample) with a metal shield. Thus, for example, the sensor may be situated in an appropriately earthed metal container, e.g. a tube of a material such as acid-resistant steel, and/or may be coated with an electrically conductive glue such as a metal epoxy glue. According to a further feature of the invention we provide a method for detection or quantification of absorption of electromagnetic radiation by a sample wherein a sensor according to the invention is irradiated to cause modulated radiation to pass along said radiation path to the said first surface and thence to said sample, heat produced by absorption of radiation by the sample being conducted to the thermal detector of said sensor to produce signals the amplitude of which is indicative of the heat produced by said absorption. The method of the invention is particularly useful in detecting or quantifying suspensions of particles, e.g. cells or aggregates, which are difficult to assay using older methods due to the problem of light scattering. The sensor and method described herein may also be utilized in the measurement of colour intensity of samples immobilised on solid supports; the signal is not subject to the disturbance by the mechanical contact between the sensor and the support which one may experience when using photoacoustic methods. The principle is similar to that employed in solution. The light is chosen at a wavelength suitable for absorption by the material in question. The increase in temperature is proportional to the colour strength and may be measured as described above. Since the technique is based on absorption rather than reflection, it is more sensitive than reflectometric methods. Furthermore, a quite small area of colour is sufficient to obtain a good signal. Coloured 2 areas less than 1 mm are normally sufficient. Some analytical techniques are based on formation of colours on a surface, either by chemical reactions leading to formation of insoluble or immobilized coloured material, or filtration of coloured agglutinates formed by coupling of receptor-ligand pairs, or by selective filtration with one member of a receptor- ligand pair immobilized in a porous material. The sensors of the invention are of particular -use in all these methods. The sensor and method according to the invention may in particular be used to detect or quantify analytes in a test sample based on alterations in the rates of sedimentation of particles due to chemical or physical interactions, as measured by, for example, determining the radiation absorption of the sample at time intervals. Further applications include analysis of blood by determination of haemoglobin in haemoc tes. In view of the small dimensions to which sensors may be made, measurements may readily be made in flow systems, e.g. where the sample contact surface of the sensor is situated within the interior of a flow chamber. Surprisingly the optometric signal is substantially unaffected by the flow of a flowing liquid sample. The invention is now more particularly described with reference to the accompanying drawings in which: Fig. 1 shows a thermal sensor according to the invention. Fig. 2 shows an arrangement for using the thermal sensor according to Fig. 1. Fig. 3 shows a complete optical sensor system wherein a sensor according to Fig. 1 is positioned in one end of an optical fibre. Fig. 4 shows a plot of the signal from a device according to Fig. 3 for various concentrations of a coloured substance dissolved in water. Fig. 5 shows a sensor consisting of a series of heat conducting elements according to Fig. 1 positioned close to each other, but not in thermal contact. Fig. 6 shows a flow chamber incorporating a thermal sensor according to the invention. Fig. 7 shows an alternative embodiment of a thermal sensor positioned on an optical fibre and a method of assembling the same. Fig. 8 shows a thermal sensor according to the invention protected by a plastic material. Fig. 9 shows a thermal sensor according to the invention which has a rounded sampling end and is protected by a plastic material. Fig. 10 shows a thermal sensor according to the invention in which the heat conductive element comprises a thin disc adhered to a block. Fig. 11 shows a plot of the results obtained by optothermal spectrometry and reflectometry in the measurement of colloidal gold immobilised on a porous membrane. Fig. 12 shows a plot of the results obtained from measurement of haemoglobin in blood against those from a standard method (Coulter S-880) . In the sensor shown in Fig. 1 the heat-conducting element 1 is a cube of transparent material with a high ability to conduct heat. Light-pulses 4 are sent through the heat-conducting element 1 and into the sample 3 mounted thereon. A proportion of the heat which is generated in the sample is conducted to the interface between the sample 3 and the heat-conducting element 1. The increase in temperature at this interface depends on the light absorbant properties of the sample. Because of the high heat-conductivity of the element 1, generated heat is conducted from the surface of the sample 3 to the thermoelectrical detector 2. The heat-conducting element 1 is of a size which allows the sample and the thermoelectrical detector to be located at a distance apart from each other which is less than or equal to the thermal diffusion length of the actual material of the heat-conducting element 1. Since the thermal diffusion length is dependent on the pulse frequency of the incoming light, the size of the heat-conducting element must be chosen with respect to the highest theoretically used frequency. As the frequency increases, the distance between the sample and the thermoelectrical detector should be decreased. In the case shown in Fig. 1, the thermoelectrical detector is a thermistor. A constant voltage is applied to the thermistor through cable leads 5. When the temperature varies, the current through thermistor, conducted via cable leads 5, will vary due to altered resistance. Using a suitable electronic arrangement the variations in current may be amplified and recorded. In the arrangement shown in Fig. 2, light from a lamp 6 is focussed through lenses 7 and 7A. Light pulses are created using a chopper 8 (a rotating disc) , and the light passes through a filter 9 in order to select a required wavelength before passing to the sample 3 through a transparent heat conducting element 1 carrying a thermistor 2 connected via cable leads 5. The wavelength and pulse frequency of the light are chosen with respect to the sample to be analysed. The electronics are locked on to the frequency of the modulated light source and the signals are then amplified. This reduces the noise and ensures that the sensor will not register variations of the temperature of the surroundings. In the arrangement shown in Fig. 3, a heat- conducting element 1 is positioned on the end of an optical fibre 11. The light source is a laser diode 10 with constant intensity and variable wavelength. The light is led from the laser diode 10 to the sample 3 through the optical fibre 11. The recorded variations in temperature depend on the variation in absorbed light at different wavelengths. One may for example change the wavelength from an absorbance maximum to a minimum. A laser diode 12 is used as thermooptical detector, its output and frequency varying with temperature. The radiation from this laser is lead through another optical fibre 13 to an optoelectrical transformer 14 where the optical signal is transformed into an electrical signal which may then be recorded. The entire sensor, except for the part which should be in contact with the sample, is covered by a protective material. The sensor is characterized by being substantially insensitive to electrical disturbances since it produces an optical output signal from the laser diode 12. The plot shown in Fig. 4, obtained using apparatus as described in connection with Fig. 3, shows a substantially linear correlation between optothermal signal and the concentration of various samples of black ink in water. The arrangement shown in Fig. 5 illustrates the possibility of combining several sensors together. The heat conducting elements 1 carry thermoelectrical detectors 2 connected to amplifiers (not shown) by cable connectors 5. They are thermally isolated from each other. Light at different wavelengths is applied via optical fibres 11 to the elements 1 which may then measure the absorbance at various wavelengths in a sample, thus providing knowledge about the absorbant properties of the various components in a sample. The concentration of each component may thereby be calculated based on the measured signal at each of the wavelengths. Another possibility is to use different modulated (e.g. pulsed) frequencies for the various sensors. Using low frequencies one may analyse a rather thick layer of a sample compared to the thin layer analysed at high frequencies. Using a proper mathematical treatment of the measured signal one may be able to analyse the concentration profile of substances situated some distance into a sample. A further possibility is to analyse a sample which shows variations from point to point. In this case the same frequency and wavelength are used in all of the sensors. The measured signals may be utilized for evaluation of variations from point to point, or they may provide a mean value for a larger surface. In the flow chamber shown in Fig. 6, solid structure 15 is formed with a flow chamber 16 having an inlet 17 and an outlet 18. A recess 19 in the structure 15 is adapted to receive a thermal sensor 20 which rests on an O-ring 21 abutting against a flange 22. The sensor 20 is pressed into contact with the O-ring 21 by springs 23 held in position by a cap 24. The sensor 20 comprises a body of cruciform vertical cross-section provided with a central, vertical, cylindrical hole into which is set a light path 25 leading to a sapphire window 26. A thermistor 27 is provided laterally to the sapphire window 26 and is connected by electrical leads 28 to the signal sensing device (not shown) . In the embodiment shown in Fig. 7, the heat conducting element 1 may for example be a sapphire rod polished to good optical quality on all surfaces. The thermal detector 2 is a thermistor preferably coated on its larger lateral faces with thin films of silver or gold to ensure good electrical connection. One such lateral face of the thermistor 2 is affixed to a vertical face of element 1 by means of silver epoxy glue. The remainder of this vertical face of element 1 and the other larger lateral face of thermistor 2 are covered with silver epoxy glue 29 whereby electrical cable connectors 5 may be attached, one to element 1 and one to thermistor 2. The remaining three vertical faces of element I are preferably also covered with silver epox glue. Element 1 may be affixed to an optical fibre II using a drop 30 of UV-curable glue and subjecting the resulting assembly to UV irradiation 31. Typical dimensions for such a sensor include element 1 (1x1x6 mm) and thermistor 2 (0.5x0.5x0.35mm) . Applying a constant voltage to thermistor 2 via leads 5, resistance changes of the order of 4% per °C may, for example, be observable. In the arrangement shown in Fig. 8 the element 1, thermistor 2 and electrical connections 5 are protected by enclosure in a tube of epoxy resin 33, leaving only the sampling end 32 of element 1 exposed. This minimises interference and consequent noise which may otherwise occur if a sample comes into electrical contact with the thermistor 2. An alternative method of protecting the sensor is shown in Fig. 9, where element 1 has a rounded sampling end 32 which, together with thermistor 2 and electrical connections 5 is protected by thin flexible plastic film 34 which in use is in thermal contact with sampling end 32 and on which sample 3 is placed. In the embodiment shown in Fig. 10, the heat conducting element is a two component system comprising a rod 35 and disc 36. These may conveniently be made of sapphire, representative dimensions including, for example, 1x1x6 mm for rod 35 and diameter 3- 5 mm and thickness 0.1-0.3 mm for disc 36. Rod 35 and disc 36 are glued together using a transparent glue and thermistors 2 are glued to the latter using silver epoxy glue. The undersides of disc 36 and thermistors 2 and the sides of rod 35 are coated with a layer of silver epoxy glue 37, a small ring at the edge of disc 36 being left uncoated. Electrical connections 5 are attached in the usual manner. Disc 36 is adhered by glue 37 to a metal, e.g. acid-resistant stainless steel, tube 38, which electrically screens or shields the sensor, and a protective coating 39 is applied. Sample 3 is irriadated by light pulses 4 passing through rod 35. By virtue of the nature of the construction of the sensor contact between sample 3 and thermistors 2 is minimal, especially when highly impermeable materials such as sapphire are used for disc 36. The following Examples illustrate the method according to the invention: Example 1 An optothermic spectrophoto eter system as shown in Fig. 2 had a transparent, conducting element 1 comprising a sapphire having a surface 2 of 1 x 1mm . The sapphire was connected to thermal sensors, and light pulses (frequency 2 Hz) were led to the sapphire through an optical fibre. The light source was a halogen lamp, and the light was filtered to give a wavelength of 540 + 40 nm. 1 q of anti-C-reactive protein monoclonal antibody formed by murine hybridoma cells was added to an activated porous membrane to immobilize the antibodies (Hybond N nylon membrane, Amersham, UK). 2 The surface area of the membrane was 10 mm in each of the measurements peformed. Solutions of C-reactive proteins varying from 0.5 to 15 ι)g/ml were added and sucked through the membrane by a negative pressure. Thereafter, a solution containing about 1 jig of another anti-C-reactive protein antibody coupled to colloidal gold with an average diameter of 4.5 nm was added and sucked through the membrane. An increasing amount of colloidal gold was arrested in the membrane as the amount of C-reactive protein was increased. The intensity of the coloured surface was measured both by reflectometry (Macbeth 1500 Plus, Reflectometer) and optothermic spectroscopy as described above. Each optothermic measurement was performed for ten seconds. The results obtained using the two methods are shown in Fig. 11 and can be seen to correlate well. Example 2 This example demonstrates how an optothermal sensor may be used for the measurement of haemoglobin in blood. 100 ul blood was added to a conically shaped test-tube containing 10 ul 20% Sterox SE. The blood was haemolyzed immediately by the detergent. The haemolyzed blood samples were measured using an instrument as described in Example 1, but now using a frequency of 16 Hz. The results from 75 blood samples were compared to a standard method (Coulter S-880) resulting in a correlation coefficient of 0.99 (Fig. 12). Repeated analyses of the same sample showed a coefficient of variation of 0.5-1.7% Example 3 The instrument of Example 2 was used with a frequency of 16 Hz. The sensor was equipped with a plastic cup which enabled blood to stay in contact with a horizontally positioned sensor. When blood was measured directly without haemolysis, the results correlated with the standard method about as well as described in Example 2. Thus, the sensor also makes direct measurements of haemoglobin in blood samples possible. Example 4 This example illustrates how the sensor may be used for the measurement of haemoglobin in a flow system. The instrument illustrated in Fig. 6 was used. The optothermal sensor 20 used had a sensitive 2 area of 1 mm and an outer diameter of 3 mm. The flow rate of blood through the chamber 16 where the sensor was positioned was 2 ml per minute. Between each sample, the chamber 16 was rinsed with a hypochlorite solution. The instrument was connected via the light path 25 to a 20 W halogen lamp and was operated at a frequency of 16.7 Hz. Each sample was measured 2-4 times over a period of 20 seconds. Twenty-six blood samples were tested using the described method, and the results were compared to a standard method for the measurement of haemoglobin using a Coulter instrument. The correlation coefficient obtained was 0.990 and the linear regression line was y = 1.04x -4.4 where y is the optothermal value, and x is the value from the standard method. The signal at the output of the amplifier attached to the sensor was also observed with an oscilloscope. No disturbances could be detected due to the blood flow.

Claims: CLAIMS: 1. A sensor for the detection or quantification of absorption of electromagnetic radiation by a sample wherein the increase of temperature induced in the sample by the radiation produces a signal proportional to said temperature increase, characterised in that the sensor comprises a heat conducting solid element which is transparent to said electro¬ magnetic radiation and which has a first surface for contacting with said sample, a radiation input surface and a radiation path between said surfaces, thermooptic or themoelectriσ thermal detector means being provided in thermal contact with said solid element close to said first surface to receive conducted heat therefrom without obstructing said radiation path. 2. A sensor as claimed in claim 1 provided with means for irradiating the sample through the solid element. 3. A sensor as claimed in claim 2 in which said means is adapted to irradiate the sample with incident radiation which is modulated with respect to amplitude and/or wavelength. 4. A sensor as claimed in claim 3 adapted whereby signals from the thermooptic or thermoelectric detector means are sampled at a frequency synchronised with the frequency of modulation of the incident radiation. 5. A sensor as claimed in any of the previous claims in which a thermistor or thermocouple or a temperature responsive laser is used as the thermal detector means. 6. A sensor as claimed in any of the previous claims in which the solid heat conducting element is made of diamond, sapphire or quartz. 7. A sensor as claimed in any of the previous claims in which the solid heat conducting element is i the form of a block with two opposed ends providing the radiation input surface and the sample contact surface, and at least one side onto which thermal detector means are mounted. 8. A sensor as claimed in claim 7 in which the sides of the block are coated with a reflective layer. 9. A sensor as claimed in any of the previous claims in which the sample contact surface of the sensor is situated within the interior of a flow chamber. 10. A method for detection or quantification of absorption of electromagnetic radiation by a sample wherein a sensor as defined in claim 1 is irradiated to cause modulated radiation to pass along said radiation path to the said first surface and thence to said sample, heat produced by absorption of radiation by the sample being conducted to the thermal detector of said sensor to produce signals the amplitude of which is indicative of the heat produced by said absorption. 11. A method as claimed in claim 10 in which the sample comprises a suspension of particles. 12. A method as claimed in claim 11 in which the sedimentation rate of the particles is measured by determining the radiation absorption thereof at time intervals. 13. A method as claimed in claim 11 in which the sample is blood and haemoglobin in haemocytes is determined. 14. A method as claimed in any of claims 11 to 13 in which the sample is a flowing liquid sample. 15. A method as claimed in claim 10 in which the sample is immobilised on a solid support.

Inventors: HELANDER PER OLOF FOLKESSON, LUNDSTROEM KURT INGEMAR, HELANDER, PER, OLOF, FOLKESSON, LUNDSTROEM, KURT, INGEMAR
Applicants: HOLMES MICHAEL JOHN, VARILAB AB, AB VARILAB, HOLMES, MICHAEL, JOHN
Application year: 1990
Main classification: G01N25
IPC codes: G01N21, G01N25, G01N33, G01R21, G01R22, G01R29