WO2009066236A1

WO2009066236A1 - Methods and systems for coupling a bio-cartridge with an optical reader

Info

Publication number: WO2009066236A1
Application number: PCT/IB2008/054827
Authority: WO
Inventors: Mark T. Johnson; Albert H. J. Immink; Marc W. G. Ponjee; Murray F. Gillies
Original assignee: Koninklijke Philips Electronics N.V.
Priority date: 2007-11-22
Filing date: 2008-11-18
Publication date: 2009-05-28

Abstract

In order to obtain an appropriate coupling in a optical sensing system (100) for sensing particle properties of particles (111) in a sample fluid (117) using frustrated total internal reflection, the cartridge (110) and/or the optical catridge reader (130) is provided with an integrated means (150) that assists in providing an optical coupling. The integrated means (150) may for example be adapted for providing an optical coupling material (152) in the gap between the cartridge (110) and the optical cartridge reader (130), for generating a low pressure or vacuum or for generating a pressure on the cartridge (110) so that a light receiving surface (114) of the cartridge (110) is pressed to an optical component (132) of the reader (130). The latter may allow the use offlat cartridges (110) as the optical component (132) for guiding the light appropriately for having frustrated total internal reflection may be present in the reader (130) rather than being part of the cartridge (110).

Description

METHODS AND SYSTEMS FOR COUPLING A BIO-CARTRIDGE WITH AN OPTICAL READER

FIELD OF THE INVENTION

The present invention relates to the field of biological, chemical or biochemical sensing. More particularly, the present invention relates to methods and systems for sensing or detecting using a cartridge and a corresponding optical reader which can operate according to the frustrated total internal reflection (FTIR) principle. The present invention furthermore relates to a corresponding method for optically coupling and a method for sensing as can be used in molecular diagnostics, biological sample analysis or chemical sample analysis. BACKGROUND OF THE INVENTION Recently frustrated total internal reflection (FTIR) has been proposed as a method to detect the binding of magnetic labels onto a biologically active substrate. Total internal reflection is an optical phenomenon that occurs when a ray of light strikes a medium boundary at an angle larger than the critical angle with respect to the normal to the surface. If the refractive index is lower on the other side of the boundary no light can pass through, so effectively all of the light is reflected. The critical angle is the angle of incidence above which the total internal reflection occurs. A side effect of total internal reflection is the propagation of an evanescent wave across the boundary surface, the evanescent wave being a nearfield standing wave exhibiting exponential decay with distance from the boundary surface. The decay length may be a few wavelengths distance from the surface 11, for example between 100 and 1000 nm. This evanescent wave leads to the phenomenon known as frustrated total internal reflection. The principle of the FTIR read-out method is illustrated in FIG. 1. Systems based on FTIR have demonstrated an ability to detect molecular concentrations approaching the nanomolar level in some test conditions. An optical substrate 10 is provided, which is preferably injection moulded and has a first major surface 11 onto which magnetic beads 12, e.g. nanobeads having a dimension between 200 and 1000 nm, can be bound. The surface 11 is an optically flat surface that is probed by an evanescent wave 13 generated by illuminating the surface 11 from the bottom with a collimated laser or LED light beam 14 under total internal reflection conditions. The illumination beam 14 is generated by a light source 15 and illuminating the surface 11 under an angle larger than the critical angle for total internal reflection. When no beads 12 are present the light is reflected from the surface and is collected on an imaging device 16 such as a photo-detector or array detector 16, e.g. a CCD. When beads 12 bind to the surface 11 the evanescent wave 13 is coupled into the beads 12 and is scattered or absorbed and thus lost for detection. Different areas of the surface 11 of the substrate 10 may be made sensitive to different biological species. The amount of light captured by the imaging device 16 will decrease in proportion to the number of beads 12 bound to the surface 11. An electromagnet 17 may be provided for attracting the magnetic beads 12, and/or for removing non-bound beads 12 before performing a measurement step.

From US 2002/0093654 Al it is known to provide a substrate that is substantially flat and separated from the optical components in the optical cartridge reader used for appropriately receiving the light from the light source and emitting the light to the detector. An index matching fluid may be provided between the cartridge and the optical coupler for improving the optical coupling and still allowing frustrated total internal reflection.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide good methods for biological, chemical or biochemical detection using frustrated total internal reflection and corresponding cartridges and/or optical cartridge readers that can be used. It is an advantage of embodiments according to the present invention that methods and systems are provided that allow using substantially flat, optionally disposable, cartridges, e.g. bio-cartridges for measuring frustrated total internal reflection. Such cartridges can be easily made, e.g. at low cost. It is an advantage of embodiments according to the present invention that cartridges and an optical cartridge reader devices are provided resulting in efficient sensing of a property of a particle of interest. It is an advantage of embodiments of the present invention that a good and stable optical coupling can be provided between the cartridge and the reader, resulting in accurate detection and/or sensing results. In embodiments of the present invention, optical cartridge readers may be provided with an optical component that is adapted so as to facilitate optical sensing using the concept of frustrated total internal reflection.

The above objective is accomplished by a method and device according to the present invention.

The present invention relates to an optical cartridge reader suitable for use with a cartridge for sensing a particle property in a sample fluid using frustrated total internal reflection, the optical cartridge reader comprising an optical component for guiding an illumination beam to the cartridge and an integrated means for assisting in providing an optical coupling between the cartridge and the optical cartridge reader. The integrated means may allow for introduction or adjustment of the optical coupling after the cartridge has been provided on an appropriate position. It is an advantage of embodiments according to the present invention that a good optical coupling between the cartridge and the optical cartridge reader can be obtained. It is an advantage of embodiments according to the present invention that deterioration of an optical coupler material due to insertion of the cartridge in the optical cartridge reader can be avoided as the optical coupler material may be introduced afterwards. It is an advantage of embodiments according to the present invention that provision of an optical coupling between the cartridge and an optical cartridge reader can be done in an easy and efficient way.

The integrated means may comprise a microfluidic channel for guiding a fluid to or from a gap between the optical cartridge reader and the cartridge, when the cartridge is positioned in the optical cartridge reader. It is an advantage of embodiments according to the present invention that the optical coupling can be performed using an optical coupling fluid already present in the cartridge or optical cartridge reader, resulting in easy manipulation and accurate optical coupling. The fluid may be an optical coupling fluid having a refractive index larger than the refractive index of the sample fluid. The optical coupling fluid may be provided in a gap between the cartridge and the optical cartridge reader thus providing an optical coupling between the two components. The microfluidic channel may be adapted for controlling flow of the fluid by capillary forces. It is an advantage of embodiments according to the present invention that the filling of the gap with optical coupling fluid may be done automatically upon positioning or insertion of the cartridge in the optical cartridge reader.

The integrated means may comprise a pumping means, for pumping a fluid to or from a gap between the optical cartridge reader and the cartridge, when the cartridge is positioned in the optical cartridge reader. It is an advantage of embodiments according to the present invention that a gap may be reduced by providing an under- pressure or vacuum or that optical coupling may be improved by filling the gap with an optical coupling fluid in a controlled way.

The integrated means may comprise a heat expandable layer adapted to fill, upon heating, a gap between the optical cartridge reader and the cartridge, when the cartridge is positioned in the optical cartridge reader. It is an advantage of embodiments of the present invention that filling of the gap can be performed in an easy and controlled way, by using heat. The integrated means furthermore may comprise a heating element for heating the heat expandable layer.

The integrated means may comprise a pressure means for pressing the cartridge towards the optical component, when the cartridge is positioned in the optical cartridge reader. It is an advantage of embodiments of the present invention that reduction of a gap between the cartridge and an optical cartridge reader can be reduced using a mechanical pressure means.

The integrated means may comprise an attraction means for attracting the cartridge towards the optical cartridge reader. The fluid may be ambient air present in a gap between the cartridge and the optical cartridge reader and the system may be adapted for removing this fluid. By removal of ambient fluid, an under-pressure or vacuum may be created so that the cartridge is pulled towards the optical cartridge reader.

The integrated means may comprise a sticking material. The integrated means may comprise a reservoir suitable for providing an immersion or fluid bath between the cartridge and the optical cartridge reader.

The optical cartridge reader may comprise a temperature reference plate and the integrated means may be adapted for providing an optical coupling material that furthermore is a thermal coupling material for thermally coupling the cartridge and the optical cartridge reader. It is an advantage of embodiments according to the present invention that both optical and thermal coupling can be performed by the same layer. It is an advantage of embodiments according to the present invention that such a coupling layer can be provide in an efficient way. It is an advantage of embodiments according to the present invention that the measurements can be performed at a predetermined reference temperature.

The present invention also relates to a cartridge suitable for use with an optical cartridge reader for sensing a particle property of particles in a sample fluid using frustrated total internal reflection, the cartridge comprising a first surface being a sensing surface where the particle property will be sensed, a second surface for receiving an illumination beam, and an integrated means for assisting in providing an optical coupling between the second surface of the cartridge and the optical cartridge reader . The first surface of the cartridge and the second surface of the cartridge may be opposite to each other. It is an advantage of embodiments according to the present invention that the means for providing appropriate optical coupling can be provided in the cartridge, without the need for making changes to existing optical cartridge readers. The integrated means may comprise a microfluidic channel for guiding a fluid to or from a gap between the optical cartridge reader and the cartridge, when the cartridge is positioned in the optical cartridge reader.

The fluid may be an optical coupling fluid having a refractive index larger than the refractive index of the sample fluid.

The microfluidic channel may be adapted for controlling flow of the fluid by capillary forces. The integrated means may comprise a pumping means, for pumping a fluid to or from a gap between the optical cartridge reader and the cartridge, when the cartridge is positioned in the optical cartridge reader.

The integrated means may comprise a heat expandable layer adapted to fill, upon heating, a gap between the optical cartridge reader and the cartridge, when the cartridge is positioned in the optical cartridge reader.

The integrated means of the cartridge may comprise a pressure means for providing a pressure between the cartridge and the optical cartridge reader. The integrated means of the cartridge may comprise sticking material. The integrated means may comprise an attraction means for attracting the optical cartridge reader to the cartridge.

The integrated means may comprise a reservoir suitable for providing an immersion or fluid bath between the cartridge and the optical cartridge reader. The present invention furthermore relates to an optical sensing device for sensing particle properties of particles in a sample fluid, the optical sensing device comprising a cartridge as described above and/or an optical cartridge reader as described above.

The present invention also relates to a method for optically coupling between a cartridge and an optical cartridge reader suitable for using frustrated total internal reflection, the method comprising obtaining the cartridge, positioning the cartridge in the cartridge reader, and providing an optical coupling between the cartridge and an optical component of the cartridge reader using an integrated means. Providing an optical coupling may be performed after or during insertion of the cartridge in the optical cartridge reader.

The optical coupling may be formed after the cartridge has been positioned in the cartridge reader.

The present invention also relates to a method for sensing a property of particles of interest in a sample in a cartridge using frustrated total internal reflection, the method comprising providing an optical coupling between a cartridge and an optical cartridge reader according to any of the methods as described above, generating an evanescent wave by providing an illumination beam under total internal reflection conditions at a sensing surface in the cartridge, probing the reflected beam, and deriving from the probed reflected beam a property of particles of interest in the sample. In one aspect, the present invention also relates to a kit of components comprising at least a sticking material and one of an optical cartridge reader suitable for use with a cartridge or a cartridge suitable for use with a cartridge reader for sensing a particle property in a sample fluid using frustrated total internal reflection, wherein the sticking material is adapted for providing an optical coupling between the cartridge and optical cartridge reader, once the sticking material is applied. The present invention also relates to a method for providing an optical coupling, the method comprising providing sticking material on at least one of the cartridge and/or the optical cartridge reader and contacting the cartridge and the optical cartridge reader. Contacting may be providing a rolling or gradual contact between the cartridge and the optical cartridge reader.

Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims. The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings. This description is given for the sake of example only, without limiting the scope of the invention. The reference figures quoted below refer to the attached drawings. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the principle of detection via frustrated total internal reflection (FTIR) as known from the prior art. FIG. 2a and FIG. 2b illustrate optical sensing systems with an integrated means for assisting in improving optical coupling wherein the integrated means is integrated in the cartridge (FIG. 2a) or in the optical cartridge reader (FIG. 2b), according to embodiments of the first aspect of the present invention.

FIG. 3 illustrates part of a detection system providing an optical coupling between the cartridge and the optical cartridge reader by providing an optical coupling layer according to a particular embodiment of the present invention.

FIG. 4a and FIG 4b illustrate effects of optical coupling layers with a non-suitable refractive index and a suitable refractive index for performing total internal reflection (FTIR) as can be used in embodiments according to the present invention. FIG. 5a and FIG. 5b show different stages during provision of an optical coupling layer according to an embodiment of the present invention.

FIG. 6 shows an example of part of an optical cartridge reader comprising an integrated cavity for providing a cartridge in an immersion or fluid bath thus providing an optical coupling between the cartridge and cartridge reader according to an embodiment of the present invention.

Fig. 7 shows a detection system with a heat transporting optical coupling whereby in the optical cartridge reader a heat reference plate is provided according to an embodiment of the present invention. DETAILED DESCRIPTION OF EMBODIMENTS

The present invention will be described with respect to particular embodiments and with reference to certain drawings but the invention is not limited thereto but only by the claims. The drawings described are only schematic and are non- limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes. The dimensions and the relative dimensions do not correspond to actual reductions to practice of the invention.

Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequence, either temporally, spatially, in ranking or in any other manner. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein. Moreover, the terms top, bottom, and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other orientations than described or illustrated herein. It is to be noticed that the term "comprising", used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. It is thus to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. Thus, the scope of the expression "a device comprising means A and B" should not be limited to devices consisting only of components A and B. It means that with respect to the present invention, the only relevant components of the device are A and B.

Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments. As the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

Furthermore, some of the embodiments are described herein as a method or combination of elements of a method that can be implemented by a processor of a computer system or by other means of carrying out the function. Thus, a processor with the necessary instructions for carrying out such a method or element of a method forms a means for carrying out the method or element of a method. Furthermore, an element described herein of an apparatus embodiment is an example of a means for carrying out the function performed by the element for the purpose of carrying out the invention.

In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the invention may be practiced without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.

Probe particles envisaged within the context of the present invention include biologically-active moieties such as but not limited to whole anti-bodies, antibody fragments such as Fab' fragments, single chain Fv, single variable domains, VHH, heavy chain antibodies, peptides, epitopes, membrane receptors or any type of receptor or a portion thereof, substrate-trapping enzyme mutants, whole antigenic molecules (haptens) or antigenic fragments, oligopeptides, oligonucleotides, mimitopes, nucleic acids and/or mixture thereof, capable of selectively binding to a potential target moiety. Antibodies can be raised to non-proteinaceous compounds as well as to proteins or peptides. These probe particles may be members of immunoreactive or affinity reactive members of binding-pairs. The nature of the target particles is determined by the nature of the target moiety to be detected. Most commonly, the particles are developed based on a specific interaction with the target moiety such as, but not limited to, antigen-antibody binding, complementary nucleotide sequences, carbohydrate-lectin, complementary peptide sequences, ligand-receptor, coenzyme, enzyme inhibitors- enzyme, etc. In the present invention, the function of a probe particle is to specifically interact with a target particle or target moiety to permit its detection. In embodiments of the present invention target particles or target moieties are the particles of interest for detecting properties, e.g. presence and/or quantity, of the analytes of interest.

The invention will now be described by a detailed description of several embodiments of the invention. It is clear that other embodiments of the invention can be configured according to the knowledge of persons skilled in the art without departing from the true spirit or technical teaching of the invention, the invention being limited only by the terms of the appended claims.

In a first aspect, the present invention relates to an optical sensing device for sensing target particle properties using frustrated total internal reflection. The optical sensing device thereby may be adapted for sensing target particle or target moiety properties of chemical, biological or bio-chemical particles. These may be analytes of interest or analyte analogues. The target particle properties may e.g. be any property of interest that will lead to an induced variation in the evanescent wave, such as for example presence or absence at the surface. By way of illustration, embodiments of the present invention not being limited thereto, an exemplary system according to an embodiment of the present invention is shown in FIG. 2a and FIG. 2b, indicating standard and optional components of the optical sensing device 100.

The optical sensing device 100 comprises a cartridge 110 having a first surface 112 being a sensing surface where the particle properties of particles 111 near or coupled to that surface will be sensed and a second surface 114 opposite thereto. The first and second surfaces 112, 114 may be surfaces of an optical substrate 116 at which the optical sensing will occur. The target particles may be present in a sample fluid 117, which, during use, may be provided in the cartridge 110. The optical substrate 116 in the cartridge may be made of any suitable material, such as for example using polystyrene material, although the invention is not limited thereto. The first surface 112 may be functionalized, e.g. for capturing particles of interest and/or probes that can bind to such particles. Different areas of the substrate may be made sensitive to different biological species. The cartridge may be any type of cartridge, such as for example a bio cartridge. In an advantageous embodiment, the second surface 114, which will be the external surface of the cartridge through which the light of the optical cartridge reader will pass and which will be facing the optical cartridge reader 130 or an optical component thereof when the cartridge is inserted in the reader 130, may be a substantially flat surface. Substantially flat thereby may mean that there exists a plane comprising substantially 50% of the surface of the cartridge facing the cartridge reader. The cartridge thus may not contain the optical features that facilitate radiation incidence angles to be used in frustrated total internal reflection (FTIR) whereby these optical features may be provided on the optical cartridge reader, more particularly in the optical component thereof. The cartridge 110 may further comprise a second substrate 118 to realise a compartment 120 where the sample 117 can be held. Alternatively, the sample 117 may be held in any suitable way such that it is able to contact the optical substrate 116, e.g. in a bottomless container positioned on the optical substrate 116. The second substrate 118 may be a flat substrate with (optionally) micro-fluidic channels either etched into the substrate or built up on top of the substrate (using for example patterned photo -resist). The cartridge main body may be made using conventional manufacturing techniques, such as for example using injection moulding.

The optical sensing device 100 furthermore comprises an optical cartridge reader 130. Such an optical cartridge reader 130 is suitable for and may be adapted for receiving the cartridge 110. The optical cartridge reader 130 comprises an optical component 132 for guiding light to and from the second surface 114 of the cartridge 110. The optical component 132 assists in optical excitation and in probing of the frustrated total internal reflection at the sensing surface 112 of a cartridge 110, e.g. bio-cartridge. Therefore an evanescent wave is generated by illuminating the sensing surface 112 of the cartridge 110 using a light source 134. The light source 134 may be part of or be external to the optical sensing device 100. It may be any suitable light source such as for example a light emitting device, a laser, etc. The optical cartridge reader 130 furthermore may be adapted for probing the sensing surface 112 using an optical detector 136 which may be a single or array detector, such as for example a photo-detector or set of detectors, a CCD detector, etc. The optical detector 136 may be part of the optical sensing device 100 or may be external thereto. The optical component 132 is adapted for receiving the light from the light source 134 and emitting the light to the light source 134 under appropriate directions with respect to the optical surfaces such that frustrated total internal reflection is not excluded as such, i.e. it is adapted for receiving the light beam under an angle larger than the critical angle for total internal reflection with respect to the sensing surface at the cartridge once it is in position. The optical component 132 therefore is adapted with a slanted optical surface making an angle with respect to the sensing surface 112 such that the incident light beam can be received orthogonal to the receiving surface. The optical component 132 thus may have a non-flat shape with surfaces oriented at an angle to the surface 114 of the cartridge 110, in order to allow light to enter into the optical component 132 at an angle suitable for optical sensing using the concept of frustrated total internal reflection. The top surface of the optical component 132 advantageously is flat and oriented parallel to the optical substrate 116 of the cartridge. When beads bind to the sensing surface 112 the evanescent wave 113 in principle is coupled into the particles at the sensing surface 112 and is scattered or absorbed and thus lost for detection. The amount of light on the optical detector 136 will decrease in proportion to the number of particles 111 bound to or present at the sensing surface 112. In order for this frustrated total internal reflection mechanism to work, a good optical coupling between the optical component 132 and the cartridge 110 needs to be present.

According to embodiments of the present invention, at least one - and optionally both - of the cartridge 110 or the optical cartridge reader 130 comprises an integrated means 150 for assisting in providing an optical coupling between the cartridge 110 and the optical cartridge reader 130. The optical coupling thereby may be improved compared to the optical coupling when no particular optical coupling is provided. The improved optical coupling may be provided after the cartridge 110 has been positioned in the optical cartridge reader 130 and optionally already during insertion of the cartridge 110 in the optical cartridge reader 130. As will be illustrated by way of example in a number of embodiments, the integrated means 150 for assisting in providing an optical coupling can be a variety of means, such as for example an integrated filling means for filling a space or gap between the cartridge 110 and the optical cartridge reader 130 with an optical coupling material, an integrated vacuum means for providing a low pressure, e.g. lower than atmospheric pressure, or vacuum between the cartridge 110 and the optical cartridge reader 130 after the cartridge 110 has been positioned in the optical cartridge reader 130, an integrated pressure means for providing a pressure on the cartridge 110 towards the optical cartridge reader 130 for reducing a spacing between the cartridge 110 and the optical cartridge reader 130, etc. The integrated means 150 may be an active means for actively adjusting or improving the optical coupling after the cartridge 110 has been introduced in the optical cartridge reader 130, i.e. the optical coupling may be adjusted after introduction of the cartridge 110. The latter is advantageous as it avoids that the optical coupling is destroyed e.g. during insertion of the cartridge 110 in the optical cartridge reader 130. The integrated means or part thereof may be integrated as a micro electro -mechnical system.

Furthermore the integrated means or part thereof may comprise electronic components that, for example, may be introduced by providing the electronic components directly on the substrate, e.g. by semiconductor processing steps like lithographic processing or thin film patterning. In particular embodiments according, the present invention also may comprise the optical coupling layer 152 provided using the integrated means 150 for assisting in providing an optical coupling. The optical coupling layer 152 may be made of a material with particular refractive index, as set out in the first embodiment of the present aspect. The optical coupling material furthermore is substantially transparent for the radiation used for performing the frustrated total internal reflection. In FIG. 2a an embodiment is shown wherein the integrated means 150 is provided in the cartridge 110, whereas in FIG. 2b an embodiment is shown wherein the integrated means 150 is provided in the optical cartridge reader 130.

In advantageous embodiments according to the present invention, the cartridge 110 and the optical cartridge reader 130 are made partly or completely dust- proof, in order to reduce or prevent dust from influencing the measurements. Furthermore, in some embodiments according to the present invention an optical coupling material 152 or low pressure or vacuum is provided also assisting in a reduction or avoidance of dust influencing the measurements. It is an advantage of embodiments according to the present invention that the function of providing a suitable light path for optical sensing using the concept of frustrated total internal reflection can be decoupled from the cartridge 110 and added as an extra optical component 132 in the optical cartridge reader 130, while maintaining an efficient optical coupling between both cartridge 110 and cartridge reader 130. In this way, the cartridge 110 become cheaper, more easily manufactured and it becomes easier to add additional functionality to the optical substrate 116.

In some embodiments, the present invention furthermore comprises a magnetic or electromagnetic field generating means 160. This magnetic or electromagnetic field generating 160 means may be used, for example where the target particles or target particles are coupled to magnetic particles or magnetic beads, for directing, controlling a position, moving, mixing, washing, etc.

In a first particular embodiment, an optical sensing device 100 as described above is provided, whereby the integrated means 150 comprises a reservoir for holding an optical coupling fluid 152. The optical coupling fluid 152 then may be provided during and/or after the cartridge 110 has been inserted in the optical cartridge reader 130. By way of example, part of an optical sensing device 100 with an integrated means 150 for providing an optical coupling fluid is shown in FIG. 3, showing the cartridge 110 after insertion into the optical cartridge reader 130 and after the optical coupling fluid has been inserted. The integrated means 150 may be present in the optical substrate 116 of the cartridge 110 or it may be present in the optical cartridge reader 130. It may for example be a microfluidic channel or another type of reservoir. The integrated means 150 furthermore may be adapted for providing the optical coupling fluid 152 in between the region or gap between the cartridge 110 and the optical cartridge reader 130. The latter may be for example performed by making the reservoir such that the capillary forces in the reservoir are smaller than the capillary forces in the gap between the cartridge 110 and the cartridge reader 130, such that once inserted, the optical coupling fluid 152 spontaneously flows in the gap. Alternatively or in addition thereto, the integrated means 150 also may comprise a pumping means for pumping the optical coupling fluid in the gap. Such a pumping unit alternatively also may be provided outside the cartridge 110 or optical cartridge reader 130 and the reservoir may be adapted to be connectable to an external pumping means. In one example, the reservoir and optionally also the optical coupling fluid 152 is present as a drop of liquid in the cartridge 110 and injected from the cartridge 110 into the space between cartridge 110 and optical component 132 once the cartridge 110 is in position, e.g. using micro-fluidic means. Capillary forces may assist in the filling process. Preferably, the fluid will be designed to evaporate once the measurement has been completed to prepare the reader for the next cartridge 110. In another example, the reservoir and optionally also the optical coupling fluid 152 may be present in the optical component 110 or elsewhere in the optical cartridge reader 130. It may for example be injected via a fluidic path in the optical component 130 into the gap or space between the cartridge 110 and the optical component 132 once or upon placing the optical cartridge 110 in place in the optical cartridge reader 130, e.g. using micro-fluidic means. Capillary forces may assist in the filling process. The optical coupling fluid 152 may be provided as a liquid. Alternatively or in addition thereto, the optical coupling fluid 152 may be provided as a vapour of an optical coupling liquid 152 whereby condensation of the vapour on the surface may provide for the optical coupling.

Condensation can be encouraged by (pre-)cooling of the cartridge 110 and/or the optical component 132. After measurement (local) heating of the cartridge 110 and/or the optical component 132 could be used to vaporise the condensed optical coupling fluid to prepare the reader for the next cartridge. The fluid used also may be designed to evaporate once the measurement has been completed to prepare the reader for the next cartridge. The optical coupling fluid 152 used advantageously will have a refractive index higher than the refractive index of the fluid in which the sample is situated. The effect thereof is shown in FIG. 4a and FIG. 4b. In FIG. 4a the situation is shown for an optical coupling fluid 152 with a refractive index lower than the refractive index of the fluid in which the sample is situated, whereby either the light will remain in the optical component 132 (solid light ray in FIG 4a) or the light will couple into the cartridge 110 but subsequently also be transmitted directly into the sample fluid (dashed light ray in FIG. 4a). In either case, it will be impossible to detect the presence of a target particles using FTIR. In most cases, the sample will be situated in a water based fluid with refractive index around 1.33, whereby a large number of materials will be suitable as coupling fluids, for examples oils. FIG. 4b illustrates the situation whereby the refractive index of the optical coupling fluid 152 provided is higher than the refractive index of the fluid in which the sample is situated resulting in successful coupling of the light between the optical component and the cartridge in a manner suitable for optical sensing using the concept of frustrated total internal reflection.

In a second particular example, the present invention relates to an optical sensing device 100 as describe above, wherein the integrated means 150 for assisting in improvement of the optical coupling is a means assisting in obtaining a low pressure, e.g. below atmospheric pressure, or vacuum between the cartridge 110 and the optical cartridge reader 130. By providing a low pressure, e.g. below atmospheric pressure, or a vacuum between the cartridge 110 and the optical cartridge reader 130 or more particularly between the second surface 114 of the cartridge 110 and the optical component 132 of the optical cartridge reader 130, the space or gap between both components 110, 130 is reduced or even avoided, resulting in improvement of the optical coupling. Such an integrated means 150 may comprise an evacuation channel, e.g. microfluidic evacuation channel, provided in the cartridge 110 and/or in the optical cartridge reader 130 through which air or other medium present between the cartridge 110 and the optical cartridge reader 130 can be removed. The integrated means 150 furthermore may comprise a pumping means connected to the evacuation channel. The pumping means may provide suction before and/or during sensing with the optical sensing system. The pumping means may be a micro electro -mechanical system (MEMS) provided in the cartridge 110 and/or the optical cartridge reader 130. Alternatively or in addition thereto, a pumping means may be present outside the cartridge 110 or the optical cartridge reader 130. The integrated means 150 of the present embodiment may be used alone or in conjunction with other optical coupling techniques as described above. The different components of the integrated means 150 may have a plurality of functionalities. For example, the evacuation channel of the present particular embodiment may, e.g. after evacuation of air or medium present, be used for providing an optical coupling fluid as described for example in the first particular embodiment.

In a third particular embodiment, the present invention provides an optical sensing device 100 as described above, wherein the integrated means 150 comprises a pressure means for providing a pressure on the cartridge after insertion of the cartridge in the optical cartridge reader such that the cartridge is pressed against the optical component. In this way the gap or space between the cartridge and the optical cartridge reader or more particularly the optical component thereof can be reduced. Such a pressure means may for example be a mechanical pressure means such as e.g. a spring or the like. It may be a micro electromechanical system (MEMS). Alternatively or in addition thereto, it may be based on another type of ferees, such as for example a magnetic pressure means providing a pressure using magnetic forces, an electrical pressure means, etc. The pressure means may be provided in the cartridge 110, e.g. at the side of the cartridge 110 that will be opposite to the side facing the optical component 132 or it may be part of the optical cartridge reader 130. The integrated means 150 of the present embodiment may be used alone or in conjunction with other optical coupling techniques as described above. In a fourth particular embodiment, the present invention provides an optical sensing device 100 as described above, wherein the integrated means 150 is adapted for providing an attractive force between the cartridge 110 and the optical cartridge reader 130. Such attractive forces may for example be magnetic forces, electric forces, etc. In one example, the cartridge 110 and the optical cartridge reader 130 may for example comprise materials that attract each other. The latter assists in reducing a gap or space between the cartridgel 10 and the optical cartridge reader 130, thus resulting in a good or improved optical coupling. The attractive force used and the corresponding integrated means 150 thereby are selected so as to result in interfering as little as possible with the assay to be performed. The integrated means 150 of the present embodiment may be used alone or in conjunction with other optical coupling techniques as described above.

In a fifth particular embodiment, an optical sensing device 100 as for example described above is provided, whereby the integrated means 150 comprises a layer of sticking material on at least one of the cartridge 110 and the optical cartridge reader 150. Such sticking material may for example be a silicone material, e.g. polydimethylsiloxane, the invention not being limited thereto. For example, any glue which is good for optical bonding may be used such as e.g. silicone-RTV, epoxy, polyurethane. The sticking material advantageously should stick better to the cartridge than to the cartridge reader. The cartridge may be adapted by providing a rough surface on the cartridge side to provide good adhesion, whereby the glue may be optically matched to avoid scattering. The integrated means 150 furthermore may be adjusted to provide a rolling contact or gradual contact between the cartridge and the optical cartridge reader such that upon contact, the air is removed as much as possible leaving little or no gaps between the cartridge, the optical coupling layer being the layer of sticking material and the optical cartridge reader. The cartridge could for example first be contacted to the sticking material on top of a cartridge reader along one edge and thereafter be slowly rotated around the point or line of contact to become more parallel to the reader. By providing such a rolling contact or gradual contact, air is forced out ahead. Progressively more of the cartridge may stick to the cartridge reader. By way of illustration, the present invention not being limited thereto, a schematic representation of providing contact between the cartridge 110 and the optical cartridge reader 130 using sticking material 151 is shown in Fig. 5a and Fig. 5b, whereby in Fig. 5a contact between the cartridge and the optical cartridge reader is illustrated that is first provided at one side and in Fig. 5b the subsequent full contact of the cartridge and the optical cartridge after providing a gradual or rolling contact is illustrated.

As discussed in the first particular embodiment, the optical coupling material 152 advantageously has a refractive index higher than that of the fluid wherein the sample to be sensed is present. For example in case of a water-based fluid having a refractive index of around 1.33, most plastic materials have a suitable refractive index. The integrated means 150 of the present embodiment may be used alone or in conjunction with other optical coupling techniques as described above. For example, the integrated means 150 may advantageously be combined with a pressure providing means providing a pressure between the cartridge 110 and the optical cartridge reader 130, as described in the third particular embodiment. In an alternative aspect of the present invention, the present invention also relates to a kit of components and corresponding method for providing an optical coupling between a cartridge and an optical cartridge reader as described in the present embodiment, wherein the sticking materials is not provided as integrated means 150 on the cartridge 110 or on the optical cartridge reader 130. The sticking material as described above may be provided as a separate component and may be applied to the cartridge or the optical cartridge reader prior to insertion of the cartridge in the cartridge reader. The alternative aspect also comprises a method for providing an optical coupling whereby first a sticking material is provided on the cartridge 110 and/or optical cartridge reader 130, whereafter the cartridge is brought in contact with the optical cartridge reader. Bringing the cartridge 110 in contact with the optical cartridge reader 130 may be performed using a method of providing a rolling or gradual contact as described above.

In a sixth particular embodiment, the present invention relates to an optical sensing device 100 as described above, wherein the integrated means 150 comprises a reservoir on at least one of the cartridge 110 or the optical cartridge reader 130 adapted for providing a fluid bath between the cartridge 110 and the optical cartridge reader 130. The reservoir may for example be formed by upstanding walls. In one example, such upstanding walls may be provided on the optical cartridge reader extending in the direction towards the cartridge, as shown by way of illustration in FIG. 6. Alternatively or in addition thereto, an integrated reservoir may be provided at the cartridge. In another example, the reservoir may be such that both cartridge and cartridge reader are immersed in the fluid for providing optical coupling. Such reservoir may be fixed to the cartridge or to the optical cartridge reader. The reservoir may be suitable for providing a liquid bath. The cartridge then may swim in the bath, whereby the fluid between the optical cartridge reader and the cartridge provides the optical coupling. The reservoir maybe suitable for providing a vapour bath, whereby condensation of the vapour on the surface provides an optical coupling layer.

Condensation can be encouraged by (pre-)cooling of the cartridge and/or the optical component. Fluids may be selected that have a high refractive index to improve the coupling efficiency. After use, a heater may be provided to evaporate the optical coupling layer formed on the optical cartridge reader, thus preparing the optical cartridge reader for further use with another cartridge. Filling of the reservoir may be done manually, automated or semi-automated and filling means may be present for assisting in filling of the reservoir. By way of illustration, embodiments of the present invention not being limited thereto, a schematic illustration of an optical cartridge reader 130 comprising a reservoir as integrated means 150 is illustrated in FIG. 6 In a seventh particular embodiment, the present invention relates to an optical sensing device 100 as described above, wherein the integrated means 150 comprises a heat expandable material being part of at least one of the cartridge 110 and or the optical cartridge reader 130. "Heat expandable material" thereby is used to refer to material capable of changing, e.g. increasing its volume at a given temperature when the temperature of the material is increased, resulting in variation of the volume of the material. The heat expandable material thereby acts as an optical coupling material 152. By heating the optical cartridge reader 130 and/or cartridge 110 when the cartridge 110 is in appropriate position, the heat expandable material fills the gap/spacing between the cartridge 110 and the optical cartridge reader 130, resulting in an improved optical coupling. By the expansion of the heat expandable material, the mechanical pressure between the two components also may be increased, such that both components may be pressed to each other, further reducing gaps or spaces between both components. Examples of heat expandable materials that may be used are thermo-plastic materials such as for example heat expandable polystyrene. Alternative materials that may be used are for example polycarbonate, polyacrylate. A further alternative may be glass. The heat expandable materials thereby advantageously should be substantially transparent for the radiation used in the optical sensing technique and have a refractive index higher than that of the fluid in which the sample is present, as described above. The integrated means further may comprise an integrated heating means for heating the expandable materials. The latter may be any type of heating means, such as e.g. a resistive element, a peltier element, etc. The heat expandable material may also be incorporated as an integral part of the optical cartridge reader, for example substrate 132, and/or of the cartridge, for example substrate 116.

In a eighth embodiment, the present invention relates to an optical sensing device 100 as described above, e.g. in any of the above embodiments, wherein the integrated means 150 furthermore is adapted for assisting in providing a thermal coupling between the cartridge 110 and the optical cartridge reader 130. The latter is advantageous as in many analysis situations it is necessary to control the temperature of the sample during the measurement. The integrated means 150 used may be the same integrated means as described for the optical coupling. In particular embodiments of the present invention wherein the integrated means 150 is adapted for providing an optical coupling material in the gap or space between the cartridge 110 and the optical cartridge reader 130, the optical coupling material may also be a thermal coupling material, i.e. having good thermal properties. In this manner, both optical and thermal coupling from the reader 130 to the sample is realised in a single layer. Furthermore, the optical cartridge reader 130 may be adapted so that a part of the optical component 132 is constructed from a material with suitable thermal properties, such as a metal like copper. The latter is by way of example illustrated in FIG. 7. In a further particular embodiment, the optical cartridge reader 130 may comprise a temperature reference plate 180, i.e. a component of relatively high thermal capacity held at a controlled temperature, and the sample may either be brought in equilibrium with the temperature reference plate 180 (passive situation) or have its temperature adjusted relative to the temperature reference plate 180 using for example integrated heating elements on the cartridge reader 130 (active situation). By way of example, an optical cartridge reader with a reference plate is illustrated in FIG. 7. The latter allows for controlling the temperature appropriately, as is required in many analysis situations. In an additional embodiment, the temperature reference plate 180 may comprise a top-coat with substantially reflective properties, such as for example a metallic thin- film (e.g. Ag, Al, Pt) or dielectric multilayer stack (e.g. alternating dielectric layers comprising silicon oxide, silicon nitride or titanium oxide). The temperature reference plate 180 furthermore may also comprise a hole to allow for the provision of magnetic fields to the sample area.

In a second aspect, the present invention relates to an optical cartridge reader 130 as described in the first aspect, i.e. without cartridge 110. The optical cartridge reader 130 thereby comprises an integrated means 150 for assisting in the optical coupling between a cartridge 110 and the optical cartridge reader 130, once the cartridge 110 is positioned in or on the optical cartridge reader 130. The integrated means 150 may have the same features and advantages as described above for the first aspect. The integrated means 150 may for example be or comprise a light coupling fluid provider for filling a space or gap between the cartridge 110 and the optical cartridge reader 130, a pressure provider for pressing the cartridge 110 to the optical cartridge reader 130 or more particularly the optical component 132 thereof, a vacuum means or pumping means for reducing the gap or space between the cartridge 110 and the optical cartridge reader 130, a heater and/or heat expandable material for filling a gap or space at least partly with expanded material, a sticking material for sticking the cartridge 110 to the optical cartridge reader 130, etc. The integrated means 150 may be an active means for improving optical coupling after the cartridge 110 has been introduced in the optical cartridge reader 130, i.e. the optical coupling may be actively improved once the cartridge 110 is at its position in the optical cartridge reader 130 by adjusting the optical coupling at that moment. Further features and advantages are as set out in the first aspect.

In a third aspect, the present invention relates to a cartridge 110 suitable to be used in an sensing device 100 for sensing biological, chemical or biochemical particles of interest. The cartridge 110 may be suitable for use with an optical sensing device 100 based on frustrated total internal reflection. The cartridge 110 comprises an integrated means 150 for assisting in the optical coupling between the cartridge 110 and an optical cartridge reader 130, once the cartridge 110 is positioned in or on the optical cartridge reader 130. Such an integrated means 150 may be required in order to guarantee a good optical coupling when the optical cartridge 110 does not comprise the optical elements for guiding the light to and from the substrate surface. The cartridge 110 may for example have a substantially flat surface at the side where the light is to be coupled in. This allows for a reduced manufacturing cost, both economic and in effort, as the more expensive optical components are not part of the cartridge 110 but are positioned in the re-usable optical cartridge reader 130. In this way, a rather inexpensive cartridge 110 can be obtained. In order to safeguard appropriate and/or accurate measurements, the optical coupling between such cartridges 110 and the optical cartridge reader 130 needs to be guaranteed such that light is appropriately guided to and from the substrate surface where the sensing is to be done. In embodiments of the present invention, this is obtained using the integrated means 150, thus allowing the use of substantially flat cartridges while still allowing the use of frustrated total internal reflection principle. The integrated means 150 may have the same features and advantages as described above for the first aspect. The integrated means 150 may for example be or comprise a light coupling fluid 152 provided for filling a space or gap between the cartridge 110 and the optical cartridge reader 130, a vacuum means or pumping means for reducing the gap or space between the cartridge 110 and the optical cartridge reader 130, a heater and/or heat expandable material for filling a gap or space at least partly with expanded material, a sticking material for sticking the cartridge 110 to the optical cartridge reader 130, etc. The integrated means 150 may be an active means for improving optical coupling after the cartridge 110 has been introduced in the optical cartridge reader 130, i.e. the optical coupling may be actively improved once the cartridge 110 is at its position in the optical cartridge reader by adjusting the optical coupling at that moment. Further features and advantages are as set out in the first aspect. As indicated above, it is an advantage of embodiments of the third aspect that low cost cartridges are provided usable for frustrated total internal reflection making the cartridges suitable for being disposable cartridges. It is an advantage of embodiments of the present invention that flat cartridges are provided usable for frustrated total internal reflection in an efficient and accurate way.

In a fourth aspect, the present invention relates to a method for providing an optical coupling between a cartridge 110 and an optical cartridge reader 130 suitable for using frustrated total internal reflection. The method comprises obtaining a cartridge 110 suitable for performing a biological, chemical or biochemical assay, positioning the cartridge 110 in a cartridge reader 130 with an optical component 132 for optically exciting and for probing particles in the cartridge 110 and providing an optical coupling between the cartridge 110 and the optical component 132 using an integrated means 150, integrated in at least one of the cartridge 110 and the optical cartridge reader 130. Providing an optical coupling facilitates optical sensing using the concept of frustrated total internal reflection. The method according to embodiments of the present comprises providing the optical coupling during insertion of the cartridge 110 and/or after insertion of the cartridge 110, i.e. once the cartridge 110 is in its appropriate position in the optical cartridge reader 130 for sensing a property of an analyte or particle of interest to be measured. The method according to embodiments of the present invention allows the use of a flat and/or disposable cartridge, e.g. bio-cartridge. Some standard or optional steps will further be described in more detail.

Obtaining a cartridge 110 suitable for performing a biological, chemical or biochemical assay may comprise constructing a cartridge 110, such as but not limited to a cartridge 110 as described above, or obtaining a pre-made version thereof. The cartridge 110 may be functionalised to perform a particular assay, i.e. provide information, e.g. particle properties, of analytes or particles of interest. The cartridge may be filled with sample either prior to or after insertion of the cartridge in the optical cartridge reader.

Inserting the cartridge 110 in the cartridge reader 130 may be performed by a sliding or shifting movement. In some embodiments the cartridge may be rolled onto a surface of the optical cartridge reader. During or after the insertion, optical coupling between the cartridge and the optical cartridge reader may be obtained using an integrated means. The latter may be performed in a plurality of ways, such as for example by performing method steps with the functionality of the device embodiments described for the first aspect. The method may for example comprise providing an optical coupling material in a gap between the cartridge and the optical cartridge reader during and/or after insertion of the cartridge. Such fluid may be provided from a micro fluidic channel in the cartridge 110 or the optical cartridge reader 130. The method for example may comprise providing a pressure on the cartridge such that the cartridge 110 and optical cartridge reader 130 are pushed against each other, thus reducing the gap or space between both components. The method also may for example comprise providing a vacuum or low pressure between the cartridge 110 and the optical cartridge reader 130 such that the cartridge 110 is pulled towards the optical cartridge reader 130 and a gap between the cartridge 110 and the optical cartridge reader 130 is reduced. The method alternatively or in addition thereto also may comprise expanding a heat expandable material, e.g. by heating a heat expandable material, in order to fill the gap between a cartridge 110 and an optical cartridge reader 130. In particular embodiments of the present invention, the method furthermore may comprise furthermore providing a thermal coupling layer for thermally coupling the cartridge and the optical cartridge reader. Furthermore, a surface of the cartridge or a sample fluid of the cartridge may be heated to obtain an appropriate temperature with respect to a reference temperature plate. In a fifth aspect, the present invention relates to a method for sensing a property of particles of interest of a sample in a cartridge using frustrated total internal reflection, wherein the method for sensing comprises providing an optical coupling between a cartridge 110 and an optical cartridge reader 130 according to the method for providing an optical coupling as described in the fourth aspect, generating an evanescent wave by providing a light beam under total internal reflection conditions at a sensing surface in the cartridge, probing the reflected beam and deriving from the probed reflected beam a property of particles of interest in the sample. Deriving from the probed reflected beam a property of particles of interest may comprise performing a predetermined algorithm or using a neural network for deriving a property of the particles from the probed reflected beam, e.g. from the measured intensity of the probed reflected beam. Deriving a property of particles of interest may comprise obtaining a qualitative parameter of the particles, i.e. for example an indication of their presence, and/or it may comprise obtaining a quantitative result, i.e. for example an indication of the concentration of particles present in the sample. According to embodiments of the present invention, the particles of interest optionally may be attached to the surface by selective binding, e.g. on a functionalised surface. The particles alternatively may be positioned near the surface by magnetic manipulation of the particles, if the particles are magnetic or are coupled to magnetic beads. The particles, prior to the binding, may optionally be coupled to a magnetic particle. Manipulation, such as mixing, positioning, removing or directing of the particles may be performed by applying a magnetic field. The method may be suitable for providing different types of assays such as for example (1-x) assays, whereby the property of particles of interest are studied by removal of particles near or at the sensing surface. The method may optionally also comprise performing a reference optical measurement prior to measurement of the sample to ensure that an appropriate or required degree of optical coupling is established. Furthermore, a plurality of reference measurements either before, after or both before and after the sample measurements may be performed.

Further features and advantages of embodiments of the current method are as described in the forth aspect.

It is an advantage of embodiments according to the present invention that the optical coupling between the cartridge and the optical cartridge reader substantially reduces or even avoids air gaps between the cartridge and the optical cartridge reader. The latter is advantageous as the evanescent wave has a decay distance in the order of several hundreds of nanometers. Therefore, the coupling efficiency decreases rapidly when air gaps larger than 100 nm are present between the cartridge and the optical parts of the reader. The optical coupling according to embodiments of the present invention therefore results in quantitative and accurate measurements by providing a reliable optical coupling.

It is an advantage of embodiments according to the present invention that cartridges are provided allowing both a good optical coupling with the optical cartridge reader and allowing easily integration of additional functionality for example electronic components such as heaters, photo-sensors, switches such as transistors, diodes etc. as the surfaces whereon these should be introduced are substantially flat.

It is to be understood that although preferred embodiments, specific constructions and configurations, as well as materials, have been discussed herein for devices according to the present invention, various changes or modifications in form and detail may be made without departing from the scope of this invention as defined by the appended claims. For example, any formulas given above are merely representative of procedures that may be used. Functionality may be added or deleted from the block diagrams and operations may be interchanged among functional blocks. Steps may be added or deleted to methods described within the scope of the present invention.

Claims

CLAIMS:

1. An optical cartridge reader (130) suitable for use with a cartridge (110) for sensing a particle property in a sample fluid using frustrated total internal reflection, the optical cartridge reader (130) comprising an optical component (132) for guiding an illumination beam to the cartridge (110) and an integrated means (150) for assisting in providing an optical coupling between the cartridge

(110) and the optical cartridge reader (130).

2. An optical cartridge reader (130) according to claim 1, wherein the integrated means (150) comprises a micro fluidic channel for guiding a fluid to or from a gap between the optical cartridge reader (130) and the cartridge (110), when the cartridge (110) is positioned in the optical cartridge reader (130), wherein the fluid is an optical coupling fluid having a refractive index larger than the refractive index of the sample fluid, wherein the microfluidic channel is adapted for controlling flow of the fluid by capillary forces.

3. An optical cartridge reader (130) according to any of the previous claims, wherein the integrated means comprises a pumping means, for pumping a fluid to or from a gap between the optical cartridge reader (130) and the cartridge (110), when the cartridge is positioned in the optical cartridge reader (130).

4. An optical cartridge reader (130) according to any of the previous claims, wherein the integrated means (150) comprises a heat expandable layer adapted to fill, upon heating, a gap between the optical cartridge reader (130) and the cartridge (110), when the cartridge is positioned in the optical cartridge reader (130).

5. An optical cartridge reader (130) according to any of the previous claims, wherein the integrated means comprises a pressure means for pressing the cartridge (110) towards the optical component, when the cartridge is positioned in the optical cartridge reader (130) and/ or wherein the integrated means comprises an attraction means for attractring the cartridge (110) towards the optical cartridge reader (130), and/ or wherein the integrated means comprises a sticking material (151), and/ or wherein the integrated means comprises a reservoir suitable for providing an immersion or fluid bath between the cartridge (110) and the optical cartridge reader (130).

6. An optical cartridge reader (130) according to any of the previous claims, wherein the optical cartridge reader (130) furthermore comprises a temperature reference plate (160) and wherein the integrated means is adapted for providing an optical coupling material that furthermore is a thermal coupling material for thermally coupling the cartridge (110) and the optical cartridge reader (130).

7. A cartridge (110) suitable for use with an optical cartridge reader (130) for sensing a particle property of particles in a sample fluid using frustrated total internal reflection, the cartridge (110) comprising a first surface (112) being a sensing surface where the particle property will be sensed, a second surface (114) for receiving an illumination beam, and an integrated means (150) for assisting in providing an optical coupling between the second surface (114) of the cartridge (110) and the optical cartridge reader (130).

8. A cartridge (110) according to claim 7, wherein the integrated means (150) comprises a microfluidic channel for guiding a fluid to or from a gap between the optical cartridge reader (130) and the cartridge (110), when the cartridge is positioned in the optical cartridge reader (130).

9. A cartridge (110) according to claim 8, wherein the fluid is an optical coupling fluid having a refractive index larger than the refractive index of the sample fluid, and wherein the micro fluidic channel is adapted for controlling flow of the fluid by capillary forces.

10. A cartridge (110) according to any of claims 7 to 9, wherein the integrated means (150) comprises a pumping means, for pumping a fluid to or from a gap between the optical cartridge reader (130) and the cartridge (110), when the cartridge is positioned in the optical cartridge reader (130).

11. A cartridge (110) according to any of claims 7 to 9, wherein the integrated means (150) comprises a heat expandable layer adapted to fill, upon heating, a gap between the optical cartridge reader (130) and the cartridge (110), when the cartridge is positioned in the optical cartridge reader (130).

12. An optical sensing device for sensing particle properties of particles in a sample fluid, the optical sensing device comprising a cartridge according to any of claims

7 to 11 and/or an optical cartridge reader according to any of claims 1 to 6.

13. A method for optically coupling between a cartridge and an optical cartridge reader suitable for using frustrated total internal reflection, the method comprising obtaining the cartridge (110) positioning the cartridge in the cartridge reader, and providing an optical coupling between the cartridge and an optical component of the cartridge reader using an integrated means.

14. A method for providing an optical coupling according to claim 13, wherein the optical coupling is formed after the cartridge has been positioned in the cartridge reader.

15. A method for sensing a property of particles of interest in a sample in a cartridge using frustrated total internal reflection, the method comprising providing an optical coupling between a cartridge and an optical cartridge reader according to the method of any of claims 13 to 14, generating an evanescent wave by providing an illumination beam under total internal reflection conditions at a sensing surface in the cartridge, probing the reflected beam, and deriving from the probed reflected beam a property of particles of interest in the sample.