WO2009087519A2

WO2009087519A2 - Wetting detection and removal

Info

Publication number: WO2009087519A2
Application number: PCT/IB2008/055405
Authority: WO
Inventors: Jeroen H. Nieuwenhuis
Original assignee: Koninklijke Philips Electronics N. V.
Priority date: 2008-01-03
Filing date: 2008-12-18
Publication date: 2009-07-16
Also published as: WO2009087519A3

Abstract

The present invention provides an optical biosensor device comprising a means for detecting the wetting of a sensor surface and/or means for removing wetting of an entrance and/or exit window of the light detection path, wherein the means comprises an infrared (IR) light source for emitting IR light having a first wavelength with a high absorption coefficient for a predetermined liquid. The present invention also refers to a method of detecting the wetting of a sensor surface of a biosensor cartridge and/or removing wetting of an entrance and/or exit window of the cartridge comprising the steps of directing IR light of known intensity into the cartridge; detecting the intensity of IR light transmitted through and/or reflected by the cartridge; calculating the amount of a predetermined absorbing liquid along the light path; and optionally directing IR light of predetermined intensity into the cartridge or onto a surface thereof for a predetermined time.

Description

WETTING DETECTION AND REMOVAL

FIELD OF THE INVENTION

The invention relates to an optical biosensor device comprising a means for detecting the wetting of a sensor surface or of an optical window and/or means for removing wetting of an optical entrance or exit window of a biosensor cartridge. The invention further relates to an optical biosensor device comprising a means for measuring the temperature within a biosensor cartridge. BACKGROUND OF THE INVENTION

The demand for biosensors is increasingly growing these days. Usually, biosensors allow for the detection of a given specific molecule within an analyte, wherein the amount of said molecule is typically small. For example, one may measure the amount of drugs or cardiac markers within saliva or blood. Therefore, target particles, for example fluorescent and/or super-paramagnetic label beads, are used which bind to a specific binding site or spot only, if the molecule to be detected is present within the analyte. There are several known optical techniques to detect these label particles bound to the binding spot. For instance, fluorescence microscopy or techniques using total internal reflection may be used for this purpose.

In general, a reliable measurement with any of these techniques requires that the fluid to be tested, e.g., saliva or blood is in complete contact with the detection or sensor surface. During injection of the sample fluid, it may be possible, e.g., due to a manufacturing error or some contamination that an air bubble gets trapped at the sensor surface and prevents sufficient or good wetting of the sensor surface. The signal or missing signal from that air bubble then leads to false test results and/or to a misinterpretation of the measurement.

In order to prevent such a false test result, it is essential to confirm the wetting of the detection or sensor surface. Preferably, this wetting detection should be simple and robust. The technical realization should also add as little costs as possible to the setup.

Whereas wetting of the sensor surface is not only desired but even necessary, wetting of any optical window, e.g., the entrance and exit window of a biosensor cartridge is to be prevented. Typically such an unintentional wetting is caused by condensation. For instance, if the cartridge had been stored in a cold location prior to use or if the measurement is performed in an outdoor application condensation could occur. However, condensation on or wetting of an optical window used to couple light into a cartridge interferes with the optical measurement and may lead to false results or interpretations.

Therefore, one should be able to detect such a wetting and to remove the wetting from the optical windows. Detection may be generally done by capacitive and/or resistive means with comb-like electrode structures near the sensor surface or the optical window. This would, however, require electrical contacts on the cartridge. In order to get rid of the wetting one could equip the detection device or the cartridge with a heater. However, this does not seem attractive considering the required power consumption. Moreover; heating the cartridge is not straightforward, since the cartridge is typically made out of a poor thermal conductor like polystyrene.

SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide an optical read-out device for biosensors to overcome the above-mentioned problems and disadvantages. In particular, it is an object to provide a device capable of detecting and/or removing wetting in order to guarantee for a correct measuring signal with improved read-out stability. This object is achieved with the features of the claims. The present invention is based on the idea to provide an optical read-out device and in particular an FTIR device that utilizes infrared (IR) light for detection and/or removal of wetting.

Accordingly, the present invention provides an optical biosensor device comprising a light source and a detector, said device being adapted to accommodate a cartridge enclosing a sample volume with a sensor surface and an optical entrance window and/or an optical exit window. Said device further comprises a means for removing the wetting of the optical entrance and/or exit window and/or a means for detecting the wetting of the sensor surface, wherein the means comprises a first infrared (IR) light source for emitting IR light having a first wavelength with a high absorption coefficient for a predetermined liquid. Optionally, i.e. depending on the application, the device further comprises an IR detector adapted to detect light of said first wavelength. The light source and the detector are arranged for an FTIR measurement, but other optical read-out techniques shall also fall under the scope of protection. Thus, wetting of said predetermined liquid may be either detected or removed by IR light, depending on the location of the wetting film. The desired wetting of the sensor surface by the sample liquid is detected by measuring the amount of absorbed IR light passing through the sample. The obstructive wetting of one or both of the optical windows of the cartridge, e.g., by condensation is removed by irradiating said wetting film with IR light of a suitable wavelength. Of course, said wetting may also be detected prior to removal.

The first wavelength may, in particular, have a high absorption coefficient for water. For example, the first wavelength may be in the range between 1900 and 2100 nm, preferably in the range between 1950 and 2000 nm. At a wavelength of about 2000 nm the absorption coefficient of water is larger than 100 cm^"1 leading to a penetration depth in water, which is smaller than 100 μm. Thus, the absorption of light by water may be used to detect its presence. Due to the small penetration depth even thin films of water, i.e. the wetting of a surface, may be detected. Alternatively, the first wavelength may be below 1500 nm.

If the wetting of a sensor surface of a biosensor-cartridge is to be checked, one may, e.g., illuminate the sample volume, which typically is a thin channel of about 100 μm thickness, with IR light. The cartridge itself has to be reasonably transparent in the respective wavelength range. A detector is placed on the other side of the cartridge. Thus, if the predetermined liquid, e.g., water is present at the region of interest, i.e. the region of illumination, a portion of the IR light will be absorbed by the water. The IR intensity measured at the detector will be reduced accordingly. If only part of the sample volume is filled, a smaller fraction of light will be absorbed.

The detected signal may also be used to calculate the temperature within the sample volume. This may be done by measuring the absorption at two different wavelengths. At one wavelength, e.g. at around 1420 nm, the absorption depends strongly on the temperature. At another wavelength, e.g. at around 1300 nm, absorption is substantially independent of the temperature. Accordingly, the temperature can be measured by calculating the ratio of the absorption at these two wavelengths.

Furthermore, the IR light may be used to heat the liquid within the sample. Thus, in combination with the above-mentioned temperature measurement an active temperature control may be provided by the device according to the invention.

The light source and the detector may be adapted to emit and detect a second wavelength, respectively in order to detect another kind of liquid having a high absorption coefficient for the second wavelength light. Said second wavelength may be, e.g., in the range between 1350 and 1650 nm, which would be suitable to detect the presence of ethanol within the cartridge. Thus, a device for measuring the amount of alcohol within a liquid analyte may be provided.

The device according to the present invention may also be used to measure the wetting on an optical window of the cartridge. As already mentioned, such a wetting is to be avoided. Thus, if wetting of an optical window is detected as described above, said wetting may be removed by IR light. Since the wavelength is chosen such that the predetermined liquid, e.g., water absorbs a large amount of the light, the wetting film may be heated which will lead to enhanced or accelerated evaporation. Thus, a condensation film may be removed effectively. For such an application, i.e. measurement of the wetting of an optical window and/or removal of said wetting, the absorption coefficient of the cartridge does not have to be taken into account, since only a surface, i.e. the optical window, is treated. Thus, a wavelength with an even better absorption by the wetting liquid may be used. For example, in the case of water a wavelength larger than about 2500 nm is preferred. In that range the absorption coefficient of water is larger than 1000 cm^"1 leading to a penetration depth, which is smaller than 10 μm. In other words: effectively all incident light is absorbed in even very thin layers of water. By this method, an optical window may be cleared from any water quickly, using at the same time a small amount of energy. This is advantageous for point-of- care applications, which are typically powered by batteries. However, the wavelength range between 1900 and 2100 nm may be used as well for this application.

Of course, the different applications may be combined in one device, which is able to detect and to remove wetting. In this case either the wavelength range between 1900 and 2100 nm may be used as a compromise or the device may comprise two separate light sources (or one light source adapted to output two wavelengths) optimized for the different applications.

The present invention also refers to a method of detecting the wetting of a sensor surface or an optical entrance and/or exit window of a biosensor cartridge and/or removing wetting of an entrance and/or exit window of the cartridge comprising the steps of directing IR light of known intensity into the cartridge or onto a surface thereof; detecting the intensity of IR light transmitted through and/or reflected by the cartridge; calculating the amount of a predetermined absorbing liquid along the light path; and optionally directing IR light of a predetermined intensity into the cartridge or onto a surface thereof for a predetermined time. Furthermore, the temperature within the cartridge may be calculated by the amount of absorption. The wavelength of the IR light is preferably in the range between 1900 and 2100 nm or above 2600 run.

The present invention further relates to an optical biosensor device comprising a light source and a detector, said device being adapted to accommodate a cartridge enclosing a sample volume with a sensor surface and an optical entrance window and/or an optical exit window, said device further comprising a means for measuring the temperature within the cartridge, wherein the means comprises a first infrared (IR) light source for emitting IR light having a first wavelength and a second infrared light source for emitting IR light having a second wavelength and at least one detector adapted to detect light of said first and second wavelengths. Preferably, the light source and the detector are arranged for an FTIR measurement, but other optical read-out techniques shall also fall under the scope of protection.

According to the present invention the first and second wavelengths are chosen such that the absorption of the first wavelength by a liquid sample filled into the cartridge depends on the temperature of said sample whereas the absorption of the second wavelength is independent of the sample temperature. For instance, in the case that the sample comprises mainly water, the first wavelength may be in the range between 1360 and 1460 nm, more preferably in the range between 1420 and 1440 nm. Alternatively, the first wavelength may be in the range between 1860 and 1940 nm, more preferably in the range between 1900 and 1920 nm. Accordingly, a preferred range for the second wavelength in case of water is in the range between 1760 and 1820 nm or alternatively below 1350 nm.

By measuring the absorption of light at the two wavelengths one may calculate the temperature of the absorbing medium, i.e. the liquid sample within the cartridge, from the ratio of both absorption values. Since the IR light from the first and/or second light source may also be used to heat the liquid sample within the cartridge by absorption, the temperature within the sample may be effectively controlled. Therefore, a controller unit may be provided as well, which is adapted to receive the output of the detector for both wavelengths, to calculate the actual temperature, to compare said temperature with a predetermined set point temperature and to control the first and/or second IR light source accordingly.

Of course, the various aspects of this invention may be combined with each other. For instance, the device for removal and/or detection of wetting may be combined with the device for measuring the temperature. For several applications it may be advantageous to be able to both remove obstructing wetting films and control the temperature for fast and accurate measurements.

These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. Ia and Ib schematically show the functional principle of an embodiment of the present invention. Fig. 2 shows a cartridge adapted for use in the present invention.

Figs. 3a and 3b show a diagram with the absorption coefficient of light in water depending on the wavelength.

Fig. 4 shows a diagram with the transmission coefficient of light depending on the wavelength for three different materials. Fig. 5 shows a diagram with the signal stability of an optical measurement versus time.

DETAILED DESCRIPTION OF EMBODIMENTS Fig. Ia schematically shows the functional principle of an embodiment of the present invention. A cartridge 1 with a channel or sample volume 2 and a sensor surface 5 is illuminated with incoming IR light 3. The light passes through the cartridge 1, the channel 2 and the sensor surface 5. If no absorbing material is present along the optical path, essentially all IR light is transmitted and the amount of transmitted light 4 is substantially equal to the amount of incoming light 3.

If an absorbing liquid, e.g., water is present as indicated in Fig. Ib, a portion of the incoming IR light 3 is absorbed and the amount of transmitted light 4 is substantially smaller than the amount of incoming light. Measuring the intensity of the transmitted light 4 allows for an estimate of the amount of absorbing material present within the channel or sample volume 2. Thus, it may be decided whether the sensor surface 5 is sufficiently wetted for a reasonable measurement.

As already mentioned, the wavelength of the IR light has to be chosen such that the liquid to be detected absorbs a lot of the IR light, whereas the material (e.g., polystyrene) of the cartridge is essentially transparent for IR light of that wavelength. Fig. 2 shows a cartridge adapted for use in the present invention. The cartridge 1 adapted to be accommodated by an FTIR device according to the present invention comprises a channel or sample volume 2 with a sensor surface 5. Furthermore, optical entrance and exit windows 6 and 7 are provided for coupling light 3' into the cartridge 1 and to allow for light 4' reflected at the sensor surface to exit the cartridge 1. For this purpose, the device comprises a first light source and a first detector (both not shown) arranged for an FTIR measurement, i.e. the light 3' illuminates the sensor surface 5 at an angle of total internal reflection. The device further comprises an IR light source (not shown) for illuminating the cartridge 1 with IR light 3. The light passes the cartridge 1 through the channel 2 and the sensor surface 5. Thus, if the sensor surface 5 is sufficiently wetted, a portion of the IR light 3 is absorbed by the wetting liquid and the intensity of the transmitted IR light 4 is reduced compared to the incoming light 3.

Alternatively or additionally, the IR light source (or a further IR light source) may be used to remove a wetting film on the optical entrance window 6 and/or the optical exit window 7. For this purpose, the illumination path 3 may be broad enough to illuminate these windows as well. Or one or more other IR light source(s) may be used to illuminate these windows. It is, for instance, also conceivable to use the illumination paths 3' and 4' for removing wetting on the optical windows.

Fig. 3 a and 3b shows the absorption coefficient of light versus wavelength for water. As can be seen the absorption coefficient is large around 1950 nm and rapidly grows above 2600 nm.

Fig. 4 depicts the transmission coefficient of light versus wavelength for polystyrene PS, polycarbonate PC and cyclic olefin polymer COP. All three materials show a rather large transmission at wavelengths below 1500 nm an in the range between about 1900 nm and 2100 nm.

Thus, a suitable regime for a selection of the wavelength of the used light, which is absorbed by water and transmitted through the plastic materials used for the cartridge, is in the range between 1900 nm and 2100 nm, in particular between 1950 nm and 2000 nm. Said range is especially useful for detecting the wetting of sensor surface 5 (Fig. 2) by water, since for this application the IR light has to pass through the plastic material of the cartridge. Therefore, it is preferred that the absorption by water of the used IR light is as high as possible, whereas at the same time the optical transmission of the cartridge material exhibits a maximum. For surface applications, e.g., the removal of wetting from an optical window, the optical properties of the cartridge material plays a minor role. If a condensation film on the optical window 6 or 7 is to be removed the IR light does not necessarily need to pass through the cartridge material without considerable absorption. Therefore, wavelengths above 2600 nm seem especially suitable, since the absorption of water beyond this value is exceptionally high.

However, it still has to be taken into account that the cartridge material does absorb IR light in said wavelength range and will thus be heated due to absorption. Thus, one has to ensure that the cartridge does not over-heat or even melt under the influence of the IR light. This could be achieved, e.g., by detecting the wetting parallel to removal thereof. Thus, as soon as the wetting film is removed the IR light may be turned off. Another option may be a timed delivery of IR light: If one knows the typical thickness of a condensation film, one may calculate or measure the amount of IR light needed for removal. Thus, a timer may stop the illumination after a predetermined time. Fig. 4 shows a diagram with the signal stability of an optical measurement versus time. Three different cartridges, which had been stored in a refrigerator (at 4°C), have been brought in a warm room, e.g., at normal conditions (around 20⁰C) and were then analyzed with an FTIR device. The intensity of the light reflected at the sensor surface of the cartridge is measured immediately after the temperature change and the corresponding signal is shown versus time in minutes. As can be seen from Fig. 4 the signal is rather small and noisy within the first 30 seconds, which is due to condensation interfering with the measurement. This clearly shows the need for an improved FTIR device, which guarantees a stable signal within a timeframe that is substantially shorter than the total measurement time. For some quick tests this means that the condensation should preferably be removed within about 5 seconds. Such a device is provided by the present invention, which simply removes the disturbing wetting film.

In addition to the improved signal stability, the present invention provides several further advantages. Only low power is needed for the IR illumination. Illumination and detection are provided with the optical read-out device. Thus, the disposable cartridges to be used can be kept cheap. No physical connection is required between device and cartridge. In particular, no electrical contacts are needed, which would also increase the costs of the cartridge. The detection/removal technique is easy to implement and can simply be expanded to further applications like a drug/alcohol test. While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. A single processor or other unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measured cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

Claims

CLAIMS:

1. Optical biosensor device comprising a light source and a detector, said device being adapted to accommodate a cartridge (1) enclosing a sample volume (2) with a sensor surface (5) and an optical entrance window (6) and/or an optical exit window

(7), said device further comprising a means for removing the wetting of the optical entrance and/or exit window, wherein the means comprises a first infrared (IR) light source for emitting IR light having a first wavelength with a high absorption coefficient for a predetermined liquid.

2. Device according to claim 1, wherein the light source and the detector are arranged for an FTIR measurement.

3. Device according to claim 1, further comprising an IR detector adapted to detect IR light of said first wavelength, the first wavelength is in the range between

1900 and 2100 nm, alternatively the first wavelength is in the range between 1950 and 2000 nm.

4. Device according to claim 1, wherein the first wavelength has a high absorption coefficient for water.

5. Device according to claim 1, wherein the first wavelength is larger than 2500 nm, the device further comprising a second IR light source for emitting IR light having a second wavelength and a second IR detector adapted to detect IR light of said second wavelength to determine the transparency of the optical windows.

6. Optical biosensor device comprising a light source and a detector, said device being adapted to accommodate a cartridge (1) enclosing a sample volume (2) with a sensor surface (5) and an optical entrance window (6) and/or an optical exit window (7), said device further comprising a means for detecting the wetting of the sensor surface (5), wherein the means comprises a first infrared (IR) light source for emitting IR light having a first wavelength with a high absorption coefficient for a predetermined liquid and an IR detector for detecting said first wavelength.

7. Device according to claim 6, wherein the light source and the detector are arranged for an FTIR measurement.

8. Device according to claim 6, wherein the first wavelength is in the range between 1900 and 2100 nm, alternatively the first wavelength is in the range between 1950 and 2000 nm, alternatively first wavelength is smaller than 1500 nm.

9. Device according to claim 6, wherein the light source is adapted to emit a second wavelength with high absorption coefficient for ethanol, wherein the second wavelength is in the range between 1350 and 1650 nm, wherein the detector is adapted to detect said second wavelength.

10. Method of detecting the wetting of a sensor surface (5) or an optical entrance and/or exit window of a biosensor cartridge (1) and/or removing wetting of the optical window (6, 7) comprising the steps of: a) directing IR light (3, 3') of known intensity into the cartridge (1) or onto a surface thereof; b) detecting the intensity of IR light (4, 4') transmitted through and/or reflected by the cartridge (1); c) determining the amount of a predetermined absorbing liquid along the light path; and d) optionally directing IR light (3, 3') of predetermined intensity into the cartridge or onto a surface thereof for a predetermined time.

11. Method according to claim 10, further comprising the step of calculating the temperature within the cartridge (1) by the amount of absorption, wherein the wavelength of the IR light is in the range between 1900 and 2100 nm, alternatively the wavelength of the IR light is in the range between 1950 and 2000 nm, and alternatively the wavelength of the IR light is larger than 2600 nm.

12. Optical biosensor device comprising a light source and a detector, said device being adapted to accommodate a cartridge (1) enclosing a sample volume (2) with a sensor surface (5) and an optical entrance window (6) and/or an optical exit window (7), said device further comprising a means for measuring the temperature within the cartridge (1), wherein the means comprises a first infrared (IR) light source for emitting IR light having a first wavelength and a second infrared light source for emitting IR light having a second wavelength and at least one detector adapted to detect light of said first and second wavelengths.

13. Device according to claim 12, wherein the light source and the detector are arranged for an FTIR measurement.

14. Device according to claim 12, wherein the first wavelength is in the range between 1360 and 1460 nm, alternatively the first wavelength is in the range between 1420 and 1440 nm, alternatively the first wavelength is in the range between 1860 and 1940 nm, alternatively the first wavelength is in the range between 1900 and 1920 nm, the second wavelength is in the range between 1760 and 1820 nm, alternatively the second wavelength is smaller than 1350 nm.

15. Device according to claim 12, further comprising a controller adapted to receive the output of the detector and to calculate the actual temperature within the cartridge from said output, the controller is adapted to compare the actual temperature with a set-point temperature and to control the first or second light source accordingly in order to control and/or stabilize the temperature of the sample volume.