DE10324973B4 - Arrangement and method for the optical detection of chemical, biochemical molecules and / or particles contained in samples - Google Patents

Abstract

arrangement for the optical detection of chemical, biochemical molecules contained in samples and / or Particles, in the light of a light source (1) over at least a partially formed as an optical waveguide sensor element (5) on a spatially resolved measuring optical detector (10) is directed, while on a interface of the optical waveguide at least one electrically conductive thin film (11) is formed, and the guided through the optical waveguide light on the interface in the field of thin film (s) (11) and / or above trained measuring surfaces (13) with angles in the range above the total reflection angle impinges, while several thin films (11) and / or measuring surfaces (13) form a series arrangement and the longitudinal axis of the row formed oriented orthogonal to the optical axis; also on Sensor element (5) on an end face for the light entry an aspherical, convex curved optically effective surface (6) is formed with the light within the sensor element (5) towards the one with the at least one thin film (11) and / or measuring surfaces (13) occupied interface focused and focused a second aspheric convex ...

Description

The The invention relates to an arrangement and a distortion to the optical Detection of sample-containing chemical, biochemical molecules and / or Particles in which, depending on the optical refractive index changing Surface plasmon resonance (SPR) for the optical detection can be exploited. With the solution according to the invention, the different analytes, in different, preferably liquid samples are included, without the use of any markers, such as For example, in conventional Fluorescence immunoassay techniques are required to be detected.

The Detection of the analyte may be based on general receptor-ligand systems, e.g. based on a variety of antigen-antibody combinations. It can in biological fluids contained proteins, molecules, Particles and other substances are detected.

The previously known solutions but have shortcomings. This concerns the very limited number of different ones Analytes that are detected simultaneously during a measurement process can.

Frequently also the required measuring accuracy has not been reached, so the reliability the analysis results are limited and corresponding evidence is not can be done with sufficiently high security.

One Another problem, the previously known for such purposes usable technical solutions are the relatively high costs, on the one hand by a increased accordingly equipment and on the other hand, the high cost of suitable Sample carrier, for security reasons Especially in medical diagnostics for single use as a "disposable" be designed have to.

Need several Individual parts in such an optical detection device before the implementation composed of a single measurement, exist considerably increased Requirements for the respective optical adjustment.

The are also described with the problems described in WO 00/46589 technical solution at least not completely solved.

Of Furthermore, from WO 03/034046 A1 a Oberflä chenplasmonen resonance sensor known in which a base unit with a light source for generating of light rays and an optical sensor unit for exciting Surface plasmons available are. Furthermore this sensor has a thin one Metal film, as measuring surface which can be brought into contact with a sample to be measured.

A similar solution is in EP 0 851 230 A1 described, which is suitable for the performance of immunoassays.

Out EP 0 341 928 A1 Also, a surface plasmon resonance sensor capable of performing biochemical and other similar tests on large sample areas is known.

The WO 92/05426 A1 discloses a biological sensor, which also has surface plasmon resonance effects, which are initiated by reflected electromagnetic radiation can, known.

One additional surface plasmon resonance sensor is described in US 2003/0107741 A1 and thereby becomes electromagnetic Radiation on a surface directed, broken at a convexly curved surface and at another interface reflected, so after a subsequent additional Refraction from the surface reflected electromagnetic radiation impinging on a detector can.

It is therefore an object of the invention, an arrangement and a method for the optical detection of different analytes, such as chemical, biochemical molecules and / or to be able to optically detect particles in samples, wherein a change the surface plasmon resonance as a result of a change exploited in the refractive index, to provide that at low Effort, low cost a sufficiently high detection security reached.

According to the invention this Task with an arrangement having the features of claim 1 and a method according to claim 20 solved. Advantageous embodiments and developments of the invention can having the features indicated in the subordinate claims be achieved.

The arrangement according to the invention for optical detection is designed such that light from a light source is directed onto an optical detector via at least one sensor element, which in turn is at least partially configured as an optical waveguide for the light. The light guide within the optical waveguide or a correspondingly formed sensor element takes place doing so in a conventional manner. To induce surface plasmon resonance, at least one electrically conductive thin film is formed on the surface of an interface on the sensor element. The thin film may be formed of various metals, preferably gold or silver, with film thicknesses in the range between 20 and 200 nm, utilizing reflectivity changes due to changes in surface plasmon resonance caused by changes in refractive index within a narrow range above the film simultaneously can be. Above such a thin layer one or more measuring surfaces, preferably for each different analyte may have been arranged or formed.

The lighting within the optical waveguide or a trained accordingly Sensor element then takes place so that the light in this area on the interface so incident that angle of incidence above the total reflection angle, below consideration predeterminable wavelengths and the respective refractive indices are maintained so that surface plasmon resonance is achieved can be.

there should be in an optical fiber, which passes through it on an optical fiber interface Reflected light reflected in focused form at least once become.

The used in the inventive arrangement Sensor element is designed so that on end faces for the light entry and the light exit respectively an aspherical, convex curved optically effective surface is trained. By means of the arranged on the light entrance side aspherical, convex curved surface can the excitation light of the light source within the sensor element or the area forming an optical waveguide focused and with the previously described angles of incidence on the interface area, on the thin film and measuring surface arranged are to be judged. Adherence to the desired angle of incidence for the light on the optical interface can by appropriate design of the aspherically curved surface below consideration the dimensioning and, accordingly, the reflection conditions within the sensor element or the optical waveguide of a Sensor element forming part done.

The aspherical, convex curved surface at the light exit side is accordingly contoured and arranged that a collimated exit of the light from the sensor element or waveguide in the direction of an optical detector achieved becomes.

One such optical detector is designed so that a spatially resolved measurement can be done. It can Accordingly, several CCD lines, a CCD matrix or a CMOS technology formed optical detector for such a spatially resolved measurement be used.

With Such an optical detector can then be spatially resolved, the light intensity as a function of Angles of incidence of the light on the aforementioned optical interface in the region of thin films and / or measuring surfaces performed and so at least one analyte to be detected qualitatively / quantitatively be detected.

One Such a sensor element, as a part but also from an optical waveguide and a lid part, which will be discussed later is, is formed or composed for single use in a suitably trained arrangement, which is essentially from another in accordance with appropriate form arranged to each other formed optical elements used and after performing analysis removed and for Health and environment harmless be disposed of.

The addressed optical arrangement can so sentlichen from two Share, namely a designated excitation and a detection part formed become.

Of the Excitation part uses at least one light source, which is preferred Monochromatic light radiates. As suitable light sources, e.g. Laser diodes or LEDs are used.

The On the one hand, the light sources used should be as incoherent as possible radiate and on the other hand have a point-like possible light exit surface.

Between Light source and the light entering the sensor element or the Fiber optic cables can further optical elements are arranged. So should in particular in cases, in which several analytes are detected simultaneously on one sensor element can be an optical aperture whose slot is slit-shaped, according to to be ordered.

Of Further, when using a non-monochromatic light source advantageous, an optical filter, which in turn preferably on the respective wavelength The bandpass filter tuned to the light used is to be arranged there.

The arrangement of a collimating opti element is advantageous, but not mandatory. In the latter case, a divergence of the light emitted by the light source, taking into account the distance of the light source or an optical aperture of the aspherically curved surface of the sensor element / waveguide, by an aspheric curvature taking into account the divergence of the light can be at least partially compensated.

Of the Use of collimated light entering and leaving the sensor element so again, but offers the advantage that one is not so highly accurate adjustment of sensor elements in relation to the others optical elements is required.

at the possible with the inventive solution simultaneous detection of different analytes or else a detection of the same analytes on different measuring surfaces, should at least the measuring surfaces be arranged at a distance to each other.

Such several thin films and / or measuring surfaces should form a series arrangement, with the individual measuring surfaces a common longitudinal axis lie. This longitudinal axis should then orthogonal to the optical axis, ie orthogonal to Beam direction of the guided by the sensor element / optical fiber light be aligned.

For the detection one or more different analytes on measuring surfaces of a sensor element / optical waveguide should if possible TM-polarized light be used.

A such TM polarization can be done by the respective light source or by means of additional therefor suitable optical elements, in the beam path of the light before but also be arranged after the sensor element / optical waveguide can, be achieved.

So can for a spatially resolved Detecting a picture of TM polarized light on the optical Detector be made. However, a normalization should be preferred the spatially resolved recorded intensities of TM polarized light with reference signals. Such Reference signals can by correspondingly also spatially resolved intensities of a Illustration of TE polarized light on one or more optical detector and the normalization by quotient be made.

The Detection of TM and TE polarized light can be local to each other separated, but also alternating at different times performed in succession become.

For this both ways can different, the light correspondingly polarizing optical Elements are used.

Becomes the sensor element irradiated with unpolarized light, so for example a polarization beam splitter can be used over the the light emerging from the sensor element / optical waveguide the two different levels polarized and onto one or the other two optical detector (s) is mapped.

Should Both the TM and the TE polarized light on an optical Detector can be the polarized in a plane light directly and the other polarized light by means of a suitable Deflection prism directed to a common optical detector become.

at Irradiation of the sensor element with polarized light exists the possibility, a polarization rotator between the light source and the light entrance to arrange in the sensor element or the optical waveguide. With the polarization rotator can by appropriate electronic Circuit an alternating polarization of the in the sensor element or optical fibers irradiated light in the two designated Polarization levels can be achieved.

It but it is also possible two correspondingly different polarizing filters alternating to move in the beam path between the light source and sensor element.

A another possibility for obtaining reference signals is at the sensor element or the optical waveguide forming part of a sensor element respectively between the measuring surfaces and / or thin films in a diagonal in relation to the interface form inclined inclined surfaces. Their angle of inclination should preferably be chosen be reflected on these surfaces Light as possible perpendicular from the sensor element / optical fiber to a corresponding there arranged additional directed to the optical detector.

Advantageous are to be used according to the invention Sensor element formed microfluidic structures. By means of this microfluidic structures may flow a fluid sample at least to respective measuring surfaces, wherein this by capillary forces but at least achievable by capillary force support.

Advantageously, the microfluidic structures are formed and arranged so that not only a corresponding sample liquid transport to measuring surfaces, but during the flowing Be a liquid sample also functionalization, sample preparation or sample modification can be carried out.

At a sensor element should as possible a sample receiving area may be present from which the sample is channeled trained microfluidic structures can flow to measuring surfaces. It should, too a receiving chamber may be present in which the liquid sample collected after detection and encapsulated in a secure form can be stored until a sensor element after use safely disposed of.

Next Sample receiving area and receiving chamber can be further areas in microstructured Form be formed. For example, an area between Sample receiving space and measuring surfaces be provided for the separation of solids from the liquid sample. Here, in such an area, for example, a membrane or be incorporated into another suitable material, so that in the liquid contained, an analysis disturbing Solids, for example, be retained by filtering.

Additionally or alone can also be another area in microstructured form be present in the targeted binding to certain analytes be initiated. But it can also be an immobilization in one be made in this area, as for example in Sandwich assays may be required. Furthermore, an active bond and thus a distance more disturbing Ingredients or a modification of certain components of the Analytes he follow.

A if necessary, sample preparation or sample modification subjected to liquid Sample then arrives at appropriately prepared measuring surfaces which then in turn complementary Partners or other suitable catcher molecules or scavengers for the respective analytes have been immobilized in advance, so that the can bind respective analyte accordingly.

As already mentioned, a sensor element but also of two interconnected individual elements, namely an optical waveguide and a lid part may be formed. On the optical fiber are then at its opposite End faces for Lichtein- and light exit the aspheric, convex curved surfaces and at least an electrically conductive thin film on the optical interface educated.

The already mentioned microfluidic structures can then on the underside of a lid part, which in turn on the optical fiber attached, and can be permanently connected to this, trained be. One so almost complete completed sensor element may in the detection of the respective Laboratory staff safely handled and following the detection be safely disposed of.

A Sample may already be contained in the sensor element.

It But there is also the possibility For example, the sample with a pipette or a cannula in one small opening in the sample receiving space of Sen sorelementes immediately before the implementation of abandon the actual analysis.

One Sensor element can before the actual detection, so one to be performed Analysis easily in a suitably trained and dimensioned Recording an arrangement according to the invention be used and at the same time a sufficiently accurate Adjustment in relation to the optical elements for light input and output be achieved, so that a handling of relatively untrained laboratory personnel readily possible is.

The Sensor elements can, which applies at least to the optical waveguide range, from a for the used light made of the light source transparent plastic become. Preferably, however, a lid part made of plastic may also be used in which case the transparency of the plastic is not is mandatory. The production can, for example by embossing, Hot stamping, but also be carried out in plastic injection molding process.

The addressed microfluidic structures can during such production into the respective workpiece imprinted, but also below, by an appropriate material removal, for example be formed using a laser.

at a sensor element formed of optical waveguide and cover part is, should the two parts as possible cohesively be connected to each other.

The already mentioned electrically conductive thin layers, at least in the area of the measuring surfaces are required by per se known CVD or PVD process on the surface an optical interface have been trained.

Sensor elements can be kept in various modifications, which in particular a targeted vote on certain Analy concerns.

So can different sample preparations or sample modifications and differently prepared measuring surfaces have been selected. Otherwise differ However, the sensor elements with respect to their design, dimensioning and in particular their optical Properties not.

following the invention will be explained in more detail by way of examples.

there demonstrate:

1 in schematic form an example of an inventive arrangement;

2 a second example of an arrangement according to the invention;

3 a third example of an arrangement according to the invention;

4 a sensor element with microfluidic structures;

5 a side sectional view through a sensor element with a plan view;

6 a side view in section of a modified sensor element with a plan view;

7A Illustrations of TM and TE polarized light on an optical detector and

7B a diagram of the detected by means of optical detector relative intensities of TM and TE polarized light as a function of the angle of incidence on the optical interface.

In 1 is an example of an arrangement according to the invention in a preferred embodiment of a sensor element 5 shown.

At the same time, light becomes a light source 1 (eg a point LED) via a collimating optical element 2 to one to a predetermined wavelength of the light of the light source 1 matched optical bandpass filter 3 (FWHM with a transmission width of 10 nm around the wavelength of the light emitted by the LED) through a slit diaphragm 4 on an aspherical, convex curved surface 6 directed the sensor element and at the optically effective surface 6 of the sensor element 5 broken and as indicated by the dashed line, on an optical interface of the sensor element 5 , which is made of transparent plastic, focused.

So in the sensor element 5 entering light is largely free of speckles.

The line focus is in the range of at least one electrically conductive thin film 11 , which is formed here of egg ner 50 nm thick gold layer arranged. On the electrically conductive thin film 11 is at least one measuring surface 13 present, are immobilized on the example, suitable for binding molecules or binding partners.

The focusing is done so that the light within the sensor element 5 in the range of thin film 11 and measuring surfaces 13 with an angle of incidence above the limit angle for total reflection. It can thus be ensured that surface-plasmon resonance can be achieved in this surface area used for the analysis.

Light reflected by this optical interface hits in divergent form on a second, again aspherical, convexly curved surface 7 of the sensor element 5 and is broken at the corresponding interface. With the refraction of this light, a collimation of the light emerging from the sensor element can be achieved.

In 1 is in optional form also a beam expansion optics 14 shown with the enlarged image on an optical detector 10 and an adaptation to the respective usable for the detection surface of the optical detector 10 can be achieved.

In a preferred embodiment, in front of the optical detector 10 a polarization beam splitter 8th arranged, with the help of TM polarized light 15 on the optical detector 10 can be directed.

TE polarized light 16 is by means of the polarization beam splitter 8th at right angles to a deflection prism 9 and, in turn, adjacent to the TM polarized light on the optical detector 10 displayed.

The optical detector 10 is to an electronic evaluation unit 18 connected, in which an evaluation can be made. In the electronic evaluation unit 18 It is then also possible to standardize the intensity values with the aid of the TM and TE polarized light intensities.

In 2 is a second example of an arrangement according to the invention, in which in particular the sensor element 5 opposite to the one at play after 1 used sensor element 5 has been modified.

The at the in 2 used example shown sensor element 5 is significantly larger area with an electrically conductive and here also the light-reflecting thin film 11 been provided.

The light of the light source 1 becomes again via a collimating optical element 2 , an optical bandpass filter 3 , an optical aperture 4 in collimated form on the sensor element 5 directed.

Of the Light enters into a planar surface area of the sensor element. The light should be at a right angle if possible on the planar surface area be directed to the sensor element. This prevents reflection of light and the homogeneity of the injected light can be improved.

Taking into account the optical refractive index of the sensor element 5 but also other angles of incidence of the light 12 These are then again the aspheric curvature of the surface 6 must take into account.

The aspherical curvature of the surface 6 is chosen so that incident light in the sensor element 5 reflected and focused at the same time. After a second reflection at the optical interface arranged below, the focused light strikes analogously as in the example 1 already described, on the optical interface (arranged here above) of the sensor element 5 to achieve surface plasmon resonance in the range of at least one measuring surface 13 ,

From this interface, the light is again on a lower optical interface and from there to a second at the light exit of the sensor element 5 arranged also aspheric, convex curved surface 7 directed the sensor element. From the surface 7 For example, the light is collimated out of the sensor element toward an optical detector 10 reflected.

This in collimated form from the sensor element 5 Reflected light can then come back through a beam-expanding optics 14 , Polarization beam splitter 8th , Deflection prism 9 , as TM and TE polarized light 15 and 16 on the optical detector 10 be directed.

This in 3 shown example of an optical detection arrangement uses a sensor element 5 as is the case with the example 1 has been described.

The light of the light source 1 is in turn via a collimating optical element 2 , an optical bandpass filter 3 , an optical slit diaphragm 4 on the light entry of the sensor element 5 arranged aspheric, convex curved surface 6 directed. Before the light hits 12 However, in this example, this light penetrates a polarization filter in combination with a voltage-controlled switchable polarization rotator 17 , By appropriate circuit, by the electronic evaluation and control unit 18 takes place alternately TM and TE polarized light in the sensor element 5 and correspondingly polarized light then also hits the optical detector offset in time 10 on, so that in time with the optical detector 10 the intensities of TM and TE polarized light detected spatially resolved and in the electronic evaluation and control unit 18 processed and evaluated.

In 4 is an example of a sensor element 5 shown in schematic form with microfluidic structural elements formed thereon.

At the sensor element 5 is a sample receiving room 20 trained, in which the sample, as already mentioned in the general part of the description, by means of a pipette or cannula but also via correspondingly suitable lines can be supplied. An area closes at this sample receiving space 21 at. In this area, solids contained in the respective liquid sample can be separated.

After this area 21 here are different areas 22 present, at which a sample modification can be achieved. For example, targeted binding with certain analyte-specific molecules can be initiated, and this also in the field 23 can be done.

Such a sample preparation or sample modification is followed by a channel 24 through which a sample passes over the measuring surfaces 13 which in turn are arranged in a row, can flow and ultimately in the receiving chamber 25 the liquid sample can be taken.

Unrecognizable electrically conductive thin films here 11 are at least below the measuring surfaces 13 educated.

In this example of a sensor element 5 For example, the measurement light used to excite surface plasmon resonance becomes the aspheric, convexly curved surface 6 coupled and occurs on the also aspheric, convex curved surface 7 from the sensor element 5 out again.

As in 4 recognizable, are accordingly the measuring surfaces 13 parallel and the arrangement of the measuring surfaces 13 orthogonal to the beam direction, so also aligned with the optical axis of the light.

The flow direction the liquid Probe is therefore at right angles in the example shown here to the beam direction of the light.

In an unillustrated form but there is also the possibility, the flow direction of the liquid sample parallel to the beam direction of the element through the sensor 5 guided light, it being particularly advantageous in this case, the liquid sample via a respective separate micro-channel to each one of the measuring surfaces 13 respectively. This can cause a mutual influence of analytes on the different measuring surfaces 13 be avoided.

5 shows in schematic form a sectional side view through a two-part sensor element 5 with attached cover part 19 , thereby forming the lower part of the sensor element 5 excluding an optical waveguide, on whose outer end faces turn the aspherical, convex curved surfaces 6 and 7 are formed.

At the optical interface of the sensor element arranged here above 5 are electrically conductive thin films 11 and on these in turn measuring surfaces 13 spaced from each other and formed in a series arrangement.

In the lid part 19 is above the measuring surfaces 13 a groove-shaped incision forming a microchannel is formed, through which the respective sample to and over the measuring surfaces 13 can flow.

The spaced array of measuring surfaces 13 is by means of the upper representation of 5 clarified.

In 6 is again a sensor element 5 , opposite to in 5 shown example of a sensor element 5 with lid part 19 has been slightly modified.

From the lower side sectional view it becomes clear that additionally at an angle obliquely inclined surfaces 26 each between adjacent measuring surfaces 13 are formed.

At these inclined surfaces 26 the light unused for the actual measurement of surface plasmon resonance excitation is reflected and as a reference signal to an optical detector 29 directed.

By means of inclined surfaces 26 can suppress diffraction effects and improved separation of signals from adjacent measurement surfaces 13 be achieved.

At a corresponding inclination angle of the inclined surfaces 26 can such an optical detector 29 immediately below the sensor element 5 to be ordered.

Between sensor element 5 and optical detector 29 can be a collimating optical element 28 to be ordered. The optical detector 29 can turn in an unrepresented form to an electronic evaluation and control unit 18 be connected and for the referencing / normalization of the measuring light, which in turn is preferably used in TM polarized form, are used.

In 7A are with the optical detector 10 captured images of TM polarized light 15 and TE polarized light 16 for individual measuring surfaces 13 shown. Here are the strip-shaped 30 and 31 in each case the TM- and TE-polarized image of a measuring surface 13 for the respective angles of incidence of the incident light in this area and reflected at the optical interface.

In 7B is a diagram of the dependent on the respective incident angle dependent detected relative intensities for a measuring surface 13 shown.

So gives the curve 30 the incident angle dependent detected intensity of TM polarized light 15 and the curve 31 the detected incident angle dependent intensity values for TE polarized light 16 again.

The curve 32 is a normalization of the curve profiles determined by quotient formation 30 and 31 ,

For the detection of analytes, the respective angle of incidence, at which an intensity minimum has been determined, can be exploited. It can be a concentration determination for analytes by means of the respective mass occupation on measuring surfaces 13 by calculation from measured values 32 be performed.

Claims (25)

Arrangement for the optical detection of chemical, biochemical molecules and / or particles contained in samples, in which light from a light source ( 1 ) via at least one sensor element which is designed in regions as an optical waveguide (US Pat. 5 ) to a spatially resolved optical detector ( 10 ) is directed, while at least one electrically conductive thin film on an interface of the optical waveguide ( 11 ) is formed, and the guided through the optical waveguide light on the interface in the region of the thin film (s) ( 11 ) and / or measuring surfaces formed above them ( 13 ) with angles in the range above the total reflection angle, thereby several thin layers ( 11 ) and / or measuring surfaces ( 13 ) form a series arrangement and the longitudinal axis of the formed row is aligned orthogonal to the optical axis; also on the sensor element ( 5 ) on an end face for the light entry an aspherical, convex curved optically active surface ( 6 ) is formed, with the light within the sensor element ( 5 ) in the direction of the at least one thin film ( 11 ) and / or measuring surfaces ( 13 Focused facing focused and a second aspherically convex curved optically active surface ( 7 ) is formed on the end face for the light exit, with the surface due to surface plasmon resonance modifi ed light in collimated form on the at least one optical detector ( 10 ). Arrangement according to claim 1, characterized in that between light source ( 1 ) and focusing surface ( 6 ) an optical aperture ( 4 ) is arranged. Arrangement according to one of the preceding claims, characterized in that in the beam path of the light a TM-polarizing optical element ( 8th . 17 ) is arranged. Arrangement according to one of the preceding claims, characterized in that in the beam path of the light, a TM and a TE polarizing optical element ( 8th . 17 ) is arranged. Arrangement according to claim 4 or 5, characterized in that the optical element is a polarization beam splitter ( 8th ). Arrangement according to one of claims 4 to 6, characterized in that in addition a deflection prism ( 9 ) is available. Arrangement according to claim 4 or 5, characterized in that the optical element is a polarization rotator ( 17 ). Arrangement according to one of the preceding claims, characterized in that between light source and sensor element ( 5 ) a collimating optical element ( 2 ) and / or an optical filter ( 3 ) is / are arranged. Arrangement according to one of the preceding claims, characterized in that a monochromatic light source ( 1 ) is available. Arrangement according to one of the preceding claims, characterized in that on the sensor element ( 5 ) between areas where thin films ( 11 ) and / or measuring surfaces ( 13 ) are formed, aligned at an obliquely inclined surfaces ( 26 ) are designed to obtain reference signals. Arrangement according to one of the preceding claims, characterized in that on the sensor element microfluidic structures ( 20 ) to ( 25 ) are designed for a capillary force related sample guide. Arrangement according to one of the preceding claims, characterized in that on the sensor element ( 5 ) a sample receiving area ( 20 ) and a receiving chamber ( 25 ) are formed. Arrangement according to one of the preceding claims, characterized in that between sample receiving area ( 20 ) and measuring surfaces ( 13 ) Structural elements ( 21 ) to ( 23 ) are designed for sample preparation or sample modification. Arrangement according to one of the preceding claims, characterized in that the microfluidic structural elements ( 20 ) to ( 25 ) at the bottom of an optical waveguide of the sensor element ( 5 ) on settable cover part ( 19 ) are formed. Arrangement according to one of the preceding claims, characterized in that on the surface of the sensor element ( 5 ) a reflective coating ( 11 ' ) and from the light source ( 1 ) on a planar surface of the sensor element ( 5 ) directed towards the thin film (s) ( 11 ) and / or measuring surface (s) ( 13 ) is reflected in focused form. Arrangement according to one of the preceding claims, characterized in that on the aspherically curved surface ( 7 ) reflected light in collimated form from a planar surface of the sensor element ( 5 ) towards the optical detector ( 10 ) exit. Arrangement according to one of the preceding claims, characterized in that the sample by separate parallel aligned microchannels to each of a measuring surface ( 13 ) is guided. Arrangement according to one of the preceding claims, characterized in that for sample preparation or sample modification a solids-separating region ( 21 ), a modification area ( 22 ) and / or a binding or Immo balancing area ( 23 ) is / are available. Arrangement according to one of the preceding claims, characterized in that the aspherically curved (n) surface (s) ( 6 and or 7 ) has / have a refractive effect. Method for the detection of sample-containing chemical, biochemical molecules and / or particles, using a device according to any one of the preceding claims, characterized in that a spatially resolved detection of the on an optical detector ( 10 ) incident light intensity as a function of the angle of incidence of the light on the interface of the sensor element ( 5 ) in the area of the thin film (s) ( 11 ) and / or measuring surface (s) ( 13 ) is carried out. Method according to claim 20, characterized in that that detection of TM polarized light is performed. Method according to claim 20 or 21, characterized that a normalization of the TM polarized light with reference signals carried out becomes. Method according to one of claims 20 to 22, characterized that for standardization TE-polarized Light is used. Method according to one of claims 20 to 23, characterized that the TM and TE polarized Light locally is detected separately from each other. Method according to one of claims 20 to 23, characterized that the TM and TE polarized Light is detected separately in time.