DE10324973A1 - Arrangement and method for the optical detection of chemical, biochemical molecules and / or particles contained in samples - Google Patents

Abstract

The invention relates to an arrangement and a method for the optical detection of chemical, biochemical molecules and / or particles contained in samples, in which the surface plasmon resonance (SPR), which changes as a function of the optical refractive index, can be used for the optical detection. In this case, light from a light source is directed onto an optical detector via at least one sensor element that is designed in some areas as an optical waveguide. At least one electrically conductive thin layer is formed below a measuring surface on an interface of this optical waveguide. The light guided through the optical waveguide strikes the interface in the area of the thin layer with angles in the area above the total reflection angle. The sensor element is designed on one end face for the light entry in such a way that an aspherical, convexly curved optically effective surface is present, with which the light within the sensor element is focused in the direction of the interface occupied by the at least one thin layer and / or measuring surface. A second aspherical, convexly curved, optically effective surface is provided on the end face of the sensor element for the light emission. By means of this optically active surface, the light modified as a result of surface plasmon resonance is directed in collimated form onto the at least one optical detector.

Description

The The invention relates to an arrangement and a method for optical Detection of chemical, biochemical molecules and / or contained in samples Particles, which differ depending on the optical refractive index changing Surface plasmon resonance (SPR) for optical detection can be used. With the solution according to the invention, the A wide variety of analytes in different, preferably liquid samples are included without the use of any marking substances, such as such as conventional ones Fluorescence immunoassay techniques are required to be detected.

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

The previously known solutions but show deficits. This affects the narrowly limited number of different ones Analytes that are detected simultaneously during a measurement process can.

Are common the required measuring accuracy has also not been achieved, so the reliability the analysis results are limited and corresponding evidence is not can be done with sufficient security.

On Another problem that can be used for such purposes technical solutions exhibit, are the relatively high costs, on the one hand by a increased accordingly equipment expenditure and on the other hand the high costs for suitable Sample carrier, the for security reasons especially in medical diagnostics for single use as a "disposable item" have to.

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

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

It is therefore an object of the invention, an arrangement and a method for optical detection of various 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 in the refractive index is used to provide that at low Effort, low costs, a sufficiently high level of detection reliability reached.

According to the invention Task with an arrangement having the features of claim 1 and a method according to claim 21 solved. Advantageous embodiments and developments of the invention can with the features designated in the subordinate claims can be achieved.

The arrangement according to the invention for optical detection is designed so that light one Light source over at least one sensor element, which in turn at least in regions as an optical fiber for the light is formed, directed to an optical detector becomes. The lighting within the optical fiber or a correspondingly trained Sensor element takes place in a manner known per se. To evoke Surface plasmon resonance is at least one electrically conductive thin layer on the sensor element on the surface an interface educated. The thin film can be made of different metals, preferably gold or silver with layer thicknesses in the range between 20 and 200 nm be, reflectivity changes due to changes the surface plasmon resonance caused by changes the refractive index within a narrow range above the thin film can be exploited at the same time. Above such a thin layer can one or more measuring surfaces, preferred for different analytes have been arranged or formed in each case his.

The lighting within the optical fiber or a correspondingly trained Sensor element then takes place so that the light in this area to the interface so that the angle of incidence is above the total reflection angle, below consideration definable wavelengths and of the respective refractive indices are observed so that surface plasmon resonance is achieved can be.

there should be in an optical fiber that passes through it to an optical interface light directed in focused form reflects at least once become.

The sensor element used in the arrangement according to the invention is designed such that on the end faces for the light entry and the An aspherical, convexly curved optically effective surface is formed in each case. By means of the aspherical, convexly curved surface arranged on the light entry side, the excitation light of the light source can be focused within the sensor element or the area forming an optical waveguide and can be directed with the previously described angles of incidence onto the interface area on which the thin film and the measuring area are arranged. The desired angle of incidence for the light on the optical interface can be maintained by appropriate design of the aspherically curved surface, taking into account the dimensioning and, accordingly, the reflection conditions within the sensor element or the part forming the optical waveguide of a sensor element.

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

On such an optical detector is preferably designed such that a spatially resolved Measurement can take place. It can accordingly several CCD lines, one CCD matrix or one Optical detector designed for this in CMOS technology spatially resolved Measurement can be used.

With Such an optical detector can then determine the light intensity as a function of location Angle of incidence of the light on the aforementioned optical interface in the area of thin layers and / or measuring surfaces carried out and at least one analyte to be detected qualitatively / quantitatively can be detected.

On such a sensor element, but also as part of an optical waveguide and a cover part, which will be discussed below is formed or composed, can be used once in an appropriately trained arrangement that essentially from others arranged in a suitable form to each other optical elements is formed, used and after analysis removed and for Harmless to health and the environment to be disposed of.

The The optical arrangement addressed can essentially consist of two Share, namely an excitation and a detection part that can be designated become.

The Excitation part uses at least one light source, which is preferred emits monochromatic light. Suitable light sources e.g. Laser diodes or light emitting diodes are used.

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

Between Light source and the light entry into the sensor element or Optical fibers can further optical elements can be arranged. So in particular in cases in which several analytes are detected simultaneously on one sensor element can be an optical diaphragm, the gap of which is slit-shaped, accordingly to be ordered.

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

The Arrangement of a collimating optical element is advantageous but not absolutely necessary. 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 from the aspherical curved surface of the Sensor element / waveguide, through a the divergence of light considering aspherical curvature at least partially be compensated.

The Use of collimated light that enters and into the sensor element so it also exits, but has the advantage that one does not such a high-precision adjustment of sensor elements in relation to the others optical elements is required.

at the possible with the solution according to the invention simultaneous detection of different analytes respectively Detection of the same analyte on different measuring surfaces should at least the measuring surfaces be arranged at a distance from each other.

Such several thin layers and / or measuring surfaces can then form a row arrangement, with the individual measuring surfaces on a common longitudinal axis lie. This longitudinal axis should then if possible orthogonal to the optical axis, also orthogonal to the beam direction of the light guided by the sensor element / optical waveguide his.

For the detection of one or more different analytes on measuring surfaces of one Sensor element / optical waveguide should use TMpolarized light if possible.

A such TM polarization can take place through the respective light source or by means of additional therefor suitable optical elements in front of the light beam or also be arranged after the sensor element / optical fiber can, can be achieved.

So can for a locally resolved Detection of an image of TM polarized light on the optical Detector can be made. However, standardization should be preferred the disbanded recorded intensities of the TM polarized light with reference signals. Such Reference signals can by means of correspondingly also spatially resolved intensities of one Imaging of TE polarized light on the or another optical detector determined and the normalization by quotient formation be made.

The Detection of TM and TE polarized light can be local from each other separately, but also alternating at different times carried out one after the other become.

For this both options can different optical polarizing accordingly Elements are used.

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

Should both the TM and the TE polarized light on an optical Light can be polarized in one plane directly and the other polarized light using a suitable one Deflection prism aimed at a common optical detector become.

at Irradiation of the sensor element with polarized light the possibility, a polarization rotator between the light source and the light entry to be arranged in the sensor element or the optical waveguide. With the polarization rotator can be replaced by appropriate electronic Circuit an alternating polarization of the in the sensor element or optical waveguide of light radiated into the two designated Polarization levels can be achieved.

It but there is also the possibility two correspondingly different polarization filters alternating to move in the beam path between light source and sensor element.

A another possibility to obtain reference signals consists in the sensor element or that part of a sensor element which forms the optical waveguide between the measuring surfaces and / or thin films in an oblique in relation to the interface to form inclined surfaces. Their angle of inclination should preferably be chosen this way be reflected on these surfaces Light if possible vertically from the sensor element / optical fiber to a corresponding there ordered additional optical detector is directed.

Advantageous are to be used on the invention Sensor element microfluidic structures formed. By means of this microfluidic structures can flow a fluid sample at least to the respective measuring surfaces, whereby this through capillary forces is at least achievable through capillary force support.

Advantageous are the microfluidic structures formed and arranged in such a way that not only a corresponding sample liquid transport to measuring surfaces, but while the pouring Movement of a liquid Sample also functionalization, sample preparation or sample modification can be done.

On a sensor element should if possible a sample receiving area from which the sample is in channel form trained microfluidic structures can flow to measuring surfaces. But it should also a receiving chamber in which the liquid sample collected after detection and encapsulated in a secure form can be kept until a sensor element after use is disposed of safely.

Next Sample receiving area and receiving chamber can further areas in microstructured Form be formed. For example, a range between Sampling room and measuring surfaces be provided for the separation of solids from the liquid sample. In such an area, for example, a membrane or another suitable material may be included, so that in the liquid included, an analysis disruptive Solids are retained, for example by filtering.

In addition or alone, a further area can also be present in microstructured form, in which bonds to specific analytes are initiated in a targeted manner. However, immobilization can also be carried out in such an area, as may be necessary, for example, in sandwich assays. Furthermore, an active Binding and thus a removal of disruptive components or a modification of certain components of the analyte he follow.

A if necessary, sample preparation or sample modification undergone liquid The sample then arrives at appropriately prepared measuring surfaces which in turn are complementary Partners or other suitable capture molecules or scavengers for the respective analytes have been immobilized in advance, so that the can connect the respective analyte accordingly.

How already mentioned, a sensor element can also consist of two interconnected individual elements, namely an optical waveguide and a cover part can be formed. Then on the optical fiber on its opposite End faces for Light entry and exit the aspherical, convex curved surfaces as well as at least an electrically conductive thin film on the optical interface educated.

The already mentioned microfluidic structures can then on the underside of a cover part, which in turn is on the optical fiber put on, and can be permanently connected to it, trained his. So almost complete Completed sensor element can be detected by the respective Laboratory personnel handled safely and after the detection be disposed of safely.

A Sample can already be contained in the sensor element.

It but there is also the possibility the sample, for example with a pipette or a cannula into a small opening in the sample receiving space of the sensor element immediately before carrying out the to abandon the actual analysis.

On Sensor element can be carried out before the actual detection, that is to say one that is Analysis easily in a suitably trained and dimensioned Inclusion of an arrangement according to the invention be used and at the same time a sufficiently accurate Adjustment in relation to the optical elements for coupling and decoupling light can be achieved, so that even relatively inexperienced laboratory personnel can handle it easily possible is.

The Sensor elements can which at least applies to the fiber optic area, from one for the used light of the light source made of transparent plastic become. However, a plastic cover part can preferably also be used be, in which case the transparency of the plastic is not is imperative. The production can, for example by embossing, Hot stamping, however also done in plastic injection molding.

The The microfluidic structures mentioned can be produced during such a production with the respective workpiece imprinted, but also subsequently, by appropriate material removal, for example using a laser.

at a sensor element, which consists of an optical fiber and a cover part the two parts should, if possible cohesively be connected to each other.

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

sensor elements can are held in various modifications, which in particular targeting specific analytes.

So can different sample preparations or sample modifications and differently prepared measuring surfaces have been selected. Otherwise make a distinction but the sensor elements with respect their design, dimensioning and especially their visual appearance Properties not.

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

there demonstrate:

1 in schematic form an example of an arrangement according to the invention;

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 top view;

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

7B a diagram of the relative intensities of TM and TE polarized light detected by means of an optical detector 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.

Thereby light becomes a light source 1 (eg a punctiform LED) via a collimating optical element 2 to a given wavelength of light from 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 of the sensor element and on the optically effective surface 6 of the sensor element 5 broken and as indicated by the broken line, on an optical interface of the sensor element 5 , which is made of transparent plastic.

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

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

The focus is such that the light inside the sensor element 5 in the area of thin film 11 and measuring surfaces 13 with an angle of incidence, above the critical angle for total reflection. This ensures that surface plasmon resonance can be achieved in this area used for the analysis.

Light reflected from this optical interface strikes a second, again aspherical, convexly curved surface in a divergent form 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 an optional beam expansion optic 14 shown with an enlarged image on an optical detector 10 and an adaptation to the respective surface of the optical detector that can be used for the detection 10 can be achieved.

In a preferred embodiment is 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 deflecting prism 9 directed and in turn by this in addition to the TM polarized light on the optical detector 10 displayed.

The optical detector 10 is connected to an electronic evaluation unit 18 connected in which an evaluation can be carried out. In the electronic evaluation unit 18 the intensity values can then also be normalized using 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 compared to that in the example below 1 used sensor element 5 has been modified.

That with the in 2 used sensor element shown example 5 is much larger with an electrically conductive and here also the light reflecting thin layer 11 been provided.

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

The Light enters a planar area of the sensor element. The light should be at a right angle if possible on the planar surface area of the sensor element are directed. This can prevent reflection of light and homogeneity of the coupled light can be improved.

Taking into account the optical refractive index of the sensor element 5 can also use other angles of incidence of light 12 are selected, which in turn is the aspherical curvature of the surface 6 have to take into account.

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

From this interface, the light is in turn directed to a lower optical interface and from there to a second at the light outlet of the sensor element 5 arranged also aspherical, convex curved surface 7 of the sensor element directed. from the surface 7 the light in collimated form from the sensor element towards an optical detector 10 reflected.

The collimated form from the sensor element 5 reflected light can then again via a beam expansion optics 14 , Polarization beam splitter 8th , Deflection prism 9 , as TM and TE polarized light 15 and 16 on the optical detector 10 be judged.

This in 3 shown example of an arrangement for optical detection uses a sensor element 5 , as in the example below 1 has been described.

The light from 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 aspherical, convex curved surface 6 directed. Before the light hits 12 in this example, however, this light penetrates a polarization filter in combination with a voltage-controlled switchable polarization rotator 17 , Through appropriate circuitry by the electronic evaluation and control unit 18 , TM and TE polarized light alternately enters the sensor element 5 and appropriately polarized light then strikes the optical detector at different times 10 on so that one after the other with the optical detector 10 the intensities of TM and TE polarized light are recorded in a spatially resolved manner and in the electronic evaluation and control unit 18 can be processed and evaluated.

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

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

After this area 21 are different areas here 22 where a sample modification can be reached. For example, specific bonds with specific analyte-specific molecules can be initiated, this also in the area 23 can be done.

A channel is connected to such a sample preparation or sample modification 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 up.

Electrically conductive thin layers not visible here 11 are at least below the measuring surfaces 13 educated.

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

As in 4 Accordingly, the measuring surfaces are recognizable 13 parallel and the row arrangement of the measuring surfaces 13 aligned orthogonally to the beam direction, i.e. also to the optical axis of the light.

The flow direction the liquid In the example shown here, the sample is therefore taken at a right angle to the direction of the light.

In a form not shown, there is also the possibility of the flow direction of the liquid sample parallel to the beam direction of the element through the sensor 5 to carry out guided light, in which case it is then particularly advantageous to use a separate microchannel to transmit the liquid sample to one of the measuring surfaces 13 respectively. As a result, there can be 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 lid part 19 , the lower part of the sensor element 5 only an optical waveguide, on the outer end faces the aspherical, convex surfaces 6 and 7 are trained.

At the optical interface of the sensor element arranged above 5 are electrically conductive thin layers 11 and on this in turn measuring surfaces 13 spaced apart and in a row 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 row arrangement of measuring surfaces 13 is shown using the upper representation of 5 clarified.

In 6 is again a sensor element 5 that compared to the in 5 shown example of a sensor element 5 with cover part 19 has been slightly modified.

From the lower sectional view on the side it is clear that surfaces inclined at an angle 26 between adjacent measurement areas 13 are trained.

On these sloping surfaces 26 the light not used for the actual measurement of the surface plasmon resonance excitation is reflected and as a reference signal to an optical detector 29 directed.

By means of the inclined surfaces 26 can suppress diffraction effects and an improved separation of signals from neighboring measuring surfaces 13 can be achieved.

With a corresponding angle of inclination of the inclined surfaces 26 can be 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, in turn, not shown, to an electronic evaluation and control unit 18 be connected and used for referencing / standardizing the measuring light, which in turn is preferably used in TM polarized form.

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. The stripes are 30 and 31 the TM and TE polarized image of a measuring surface 13 for the respective angles of incidence of the light incident in this area and reflected at the optical interface.

In 7B is a diagram of the relative intensities for a measuring surface which are detected as a function of the respective angle of incidence 13 shown.

So there is the curve 30 the intensity of TM-polarized light as a function of the angle of incidence 15 and the curve 31 the detected angle of incidence dependent intensity values for TE-polarized light 16 again.

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

The respective angle of incidence at which an intensity minimum has been determined can be used for the detection of analytes. A concentration determination for analytes can be carried out by means of the respective mass occupancy on measuring surfaces 13 by calculation from measured values 32 be performed.

Claims (26)

Arrangement for the optical detection of chemical, biochemical molecules and / or particles contained in samples, in which light from a light source is directed onto an optical detector via at least one sensor element designed in some areas as an optical waveguide, at least one electrically conductive thin layer below an optical fiber at an interface Measuring surface is formed, and the light guided through the optical waveguide strikes the interface in the area of the thin layer (s) and / or the measuring area (s) with angles in the area above the total reflection angle, characterized in that on the sensor element ( 5 ) an aspherical, convexly curved optically effective surface on one end for the entry of light ( 6 ) is designed with which light within the sensor element ( 5 ) towards those with the at least one thin layer ( 11 ) and / or measuring surface ( 13 ) occupied interface focused and a second aspherically convex curved optically effective surface ( 7 ) is formed on the end face for the light exit, with which modified light due to surface plasmon resonance in collimated form on at least one optical detector ( 10 ) is directed. Arrangement according to claim 1, characterized in that between the light source ( 1 ) and focusing surface ( 6 ) an optical aperture ( 4 ) is arranged, at least two thin layers on the interface ( 11 ) and / or measuring surfaces ( 13 ) are arranged at a distance from each other and a spatially resolved optical detector ( 10 ) is used. Arrangement according to claim 1 or 2, characterized characterized that several thin layers ( 11 ) and / or measuring surfaces ( 13 ) form a row arrangement and the longitudinal axis of the row formed is aligned orthogonally to the optical axis. 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 ) is. 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 ) is. Arrangement according to one of the preceding claims, characterized in that between the 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 layers ( 11 ) and / or measuring surfaces ( 13 ) are formed, surfaces aligned at an obliquely inclined angle ( 26 ) are designed to obtain reference signals. Arrangement according to one of the preceding claims, characterized in that microfluidic structures ( 20 ) to ( 25 ) are designed for sample guidance due to capillary force. Arrangement according to one of the preceding claims, characterized in that on the sensor element ( 5 ) a sample collection area ( 20 ) and a reception chamber ( 25 ) are trained. Arrangement according to one of the preceding claims, characterized in that between the sample receiving area ( 20 ) and measuring surfaces ( 13 ) Structural elements ( 21 ) to ( 23 ) are trained for sample preparation or sample modification. Arrangement according to one of the preceding claims, characterized in that the microfluidic structural elements ( 20 ) to ( 25 ) on the bottom of an on the optical fiber of the sensor element ( 5 ) attachable cover part ( 19 ) are trained. Arrangement according to one of the preceding claims, characterized in that on the surface of the sensor element ( 5 ) a reflective coating ( 11 ' ) is formed and from the light source ( 1 ) on a planar surface of the sensor element ( 5 ) directed light towards the thin film (s) ( 11 ) and / or measuring surface (s) ( 13 ) is reflected in a focused form. Arrangement according to one of the preceding claims, characterized in that on the aspherically curved surface ( 7 ) reflected light in a 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 means of separate microchannels aligned parallel to one another to a respective measuring surface ( 13 ) is performed. Arrangement according to one of the preceding claims, characterized in that an area separating solids (for sample preparation or sample modification ( 21 ), a modification area ( 22 ) and / or a binding or immobilization area ( 23 ) is / are. Arrangement according to one of the preceding claims, characterized in that the aspherically curved surface (s) (s) ( 6 ) and or ( 7 ) has / have a refractive effect. Method for the detection of chemical, biochemical molecules and / or particles contained in samples, using a device according to one of the preceding claims, characterized in that a spatially resolved detection of the 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. A method according to claim 21, characterized in that TM polarized light detection is performed. A method according to claim 21 or 22, characterized in that a normalization of the TM polarized light with reference signals by to be led. Method according to one of claims 21 to 23, characterized in that that TE polarized for normalization Light is used. Method according to one of claims 21 to 24, characterized in that that the TM and TE polarized Local light is detected separately from one another. Method according to one of claims 21 to 24, characterized in that that the TM and TE polarized Light is detected separately in time.