DE102020216450A1 - Device and method for detecting at least one substance - Google Patents

Abstract

The invention relates to a device (1) for detecting at least one substance (2), having: a photonic crystal (5) with a surface (5a) which has at least one detection area and at least one reference area, the substance to be detected being in the detection area (2) can be accumulated and the substance (2) to be detected cannot be accumulated in the reference region, with the accumulation of the substance (2) to be detected causing a resonance (17) in the transmission and/or reflection spectrum of the photonic crystal (5) shifted spectrally in the detection area relative to the reference area, a light source (3) for irradiating light (4) onto the surface (5a) of the photonic crystal (5) and a detector (6) for measuring a first intensity signal (ID) of the in the detection area of the surface (5a) of the photonic crystal (5) reflected or transmitted light (4a) and for measuring a second intensity signal (I R) of the light (4a) reflected or transmitted in the reference area of the surface (5) of the photonic crystal (IR). In its spectrum, the light source (3) has at least one flank that can be spectrally tuned in the region of resonance (17) of the photonic crystal (5). Alternatively, the light source (3) is broadband and the device (1) comprises a spectral filter (20) that can be modulated for filtering the reflected or transmitted light (4a), wherein the filter spectrum of the spectral filter (20) has at least one flank that is in the range of the resonance of the photonic crystal (5) is spectrally tunable. The device (1) also has an evaluation device (7) which is designed to detect the substance (2) by comparing the first intensity signal (ID) measured during the tuning with the second intensity signal (IR) measured during the tuning. The invention also relates to an associated method.

Description

The invention relates to a device for detecting at least one substance, comprising: a photonic crystal with a surface which has at least one detection area and at least one reference area, the substance to be detected being able to be deposited in the detection area and the substance to be detected not being able to be deposited in the reference region is, whereby the addition of the substance to be detected causes a resonance in the transmission and/or reflection spectrum of the photonic crystal in the detection area to be spectrally shifted relative to the reference area, a light source for irradiating light onto the surface of the photonic crystal, and a detector for Measurement of a first intensity signal of the light reflected or transmitted in the detection area of the surface of the photonic crystal and for measuring a second intensity signal of the light reflected in the reference area of the surface of the photonic crystal ref reflected or transmitted light.

The invention also relates to a method for detecting at least one substance, comprising the steps of: irradiating light onto a surface of a photonic crystal, the surface having at least one detection area and at least one reference area, with the substance to be detected accumulating in the detection area and in the reference area does not attach, with the attachment of the substance to be detected causing a resonance in the transmission and/or reflection spectrum of the photonic crystal in the detection area to be shifted spectrally relative to the reference area, and measuring a first intensity signal of the light reflected or transmitted in the detection area of the surface of the photonic crystal and measuring a second intensity signal of the light reflected or transmitted in the reference area of the surface of the photonic crystal.

The substance that accumulates on the surface in the detection area can be a biological substance, for example. In order to be able to attach a biological substance, the surface of the photonic crystal in the detection area is usually functionalized with biological/organic substances. According to the lock and key principle, a suitable biological substance, e.g. an antibody, can dock to the functionalized detection area of the surface, which leads to a change in the refractive index in the immediate vicinity of the detection area on the surface. This change in refractive index means that a resonance in the transmission and/or reflection spectrum of the photonic crystal in the detection area shifts spectrally relative to the same resonance in the transmission and/or reflection spectrum of the photonic crystal in the reference area. The resonance in the reference area does not shift when the substance is present on the surface, since the reference area is not functionalized, so that the substance to be detected does not accumulate in the reference area.

The spectral shift of the resonance in the transmission and/or reflection spectrum of the photonic crystal can be detected, for example, by analyzing the transmission and/or reflection spectrum of the photonic crystal with a spectrometer. However, a measurement setup used for this purpose is complex and associated with high costs.

Another approach to the detection of biological substances using the spectral shift of resonances in the transmission and / or reflection spectrum of a photonic crystal is in WO 2011/091781 A1 described. There, a light source, which radiates light into a photonic crystal brought into contact with the substance, is tuned to the photonic crystal in such a way that the resonances caused by the photonic crystal and the resonances caused by the interaction of the photonic crystal with the substance occur in a flank area of the Emission spectrum of the light source are. If the spectral position of the resonances in the spectrum of the photonic crystal changes, the intensity of the light detected by the detector also changes. In this way, the resonance shift is translated into an intensity change. At the in the WO 2011/091781 A1 described device is therefore sufficient to detect an accumulation of the substance on the surface of the photonic crystal a simple intensity measurement.

At the in the WO 2011/091781 A1 In the measurement described, it is not readily possible to differentiate between changes in intensity that are due to the accumulation of the substance and changes in intensity that are due to other influencing factors, eg fluctuations in the intensity of the light from the light source.

In the article "Handheld imaging photonic crystal biosensor for multiplexed, label-free protein detection" by S. Jahns et al., Biomedical Optics Express, Vol. 10, it is proposed that, in addition to the functionalized areas, reference areas be in the form of non-functionalized areas to be used on which the substances to be detected cannot accumulate. The reference areas make it possible to eliminate fluctuations and/or drift in the measured intensity, which affect the detection areas and the reference areas alike. Position-dependent fluctuations and/or drift in the measurement can also be eliminated if a respective non-functionalized reference area is arranged adjacent to a functionalized detection area. For example, the reference area can surround the detection area in a ring.

It has been shown that, despite the use of the reference ranges, the signal-to-noise ratio of such a measurement is generally not sufficient for reliable detection of substances that accumulate on the surface in very small amounts.

It is the object of the invention to provide a device and a method that enable simple, inexpensive and reliable detection of even the smallest amounts of a substance.

According to a first aspect, this object is achieved by the device mentioned at the outset, in which the light source has at least one edge in its spectrum that is spectrally tunable in the resonance range of the photonic crystal, or in which the light source is broadband and the device has a modulable edge Spectral filter for filtering the light reflected or transmitted in the detection area and in the reference area of the surface of the photonic crystal, wherein the filter spectrum of the spectral filter has at least one edge, the range of resonance of the photonic crystal is spectrally tunable, and in which the device has a Has an evaluation device which is designed to detect the substance by comparing the first intensity signal measured during the tuning with the second intensity signal measured during the tuning.

Compared to the intensity-based devices and methods from the prior art, tuning the edge in the spectrum of the light source leads to a significantly higher signal-to-noise ratio and thus allows significantly smaller amounts of substance to be reliably detected. From a mathematical perspective, the measured intensity signals can be interpreted as the result of a convolution of the spectrum of the light source with the transmission or reflection spectrum of the photonic crystal in the resonance range. The high signal-to-noise ratio is a consequence of the fact that the entire transmission and reflection spectrum in the resonance range is reflected in the measured intensity signals. This is in marked contrast to that in WO 2011/091781 A1 described device, in which only a weighted integral over the transmission spectrum of the photonic crystal in the resonance range is included in the evaluation. The above reasoning applies analogously to the alternative in which the light source is broadband and the device comprises a spectral filter that can be modulated for filtering the light reflected or transmitted by the surface of the photonic crystal.

In one embodiment, the evaluation device is designed to determine a shift of an edge of the first intensity signal measured during the tuning relative to a corresponding edge of the second intensity signal measured during the tuning when comparing the intensity signals.

The shift in resonance in the transmission or reflection spectrum of the photonic crystal caused by the accumulation of the substance in the detection area is expressed in the shift of an edge of the first intensity signal measured during the tuning relative to a corresponding edge of the second intensity signal measured during the tuning. The substance can therefore be detected via the relative shift of the flank in the first intensity signal to the corresponding flank in the second intensity signal. This relative shift of the edges can be determined by using the distance in the values of the arguments of the intensity signals, which correspond to a certain proportion of the saturation values or the maximum values of the respective (normalized) intensity signals. Alternatively, this relative displacement of the flanks can be determined, for example, by determining the distance between two straight lines that are fitted to the flanks. It goes without saying that the relative displacement between the two flanks can also be determined in another way.

The substance can be detected, for example, by comparing the distance between the flanks or the amount of displacement with a threshold value and inferring that the substance has accumulated if the threshold value is exceeded. It is also possible to observe the course over time of the amount of displacement during repeated, generally continuous, tuning of the edge in the resonance range. In this case, for example, the accumulation of the substance to be detected can can be recognized from an increase over time in the amount of displacement.

In a further embodiment, the evaluation device is designed to determine the concentration of the substance to be detected by means of a relationship determined by calibration between the shift of the edge of the first intensity signal measured during the tuning relative to the corresponding edge of the second intensity signal measured during the tuning and the concentration of the substance to be detected. The relationship between the concentration of the substance and the amount of relative displacement between the two flanks can be determined, for example, by bringing a liquid containing the substance at a known concentration into contact with the surface and determining the associated value of the displacement becomes. In this case, the known concentration of the substance in the liquid is not determined in the manner described above. If this process is repeated several times with liquids containing different, known concentrations of the substance, a relationship between the concentration of the substance in the liquid and the amount of the shift can be determined in the form of a calibration curve.

In a further embodiment, the light source comprises a broadband primary light source and a spectral filter, preferably an edge filter or a bandpass filter, which generates the flank in the spectrum of the light source, the spectral filter being modulated in order to reduce the flank in the spectrum of the light source in the region of resonance of the photonic crystal tune spectrally. It is favorable for the detection of the substance if the spectral filter has at least one very steep edge. The spectral tuning of a single edge of the spectral filter in the resonance range of the photonic crystal is sufficient for the detection, so that an edge filter with the steepest possible edge can be used as the spectral filter. It is not detrimental to the detection of the substance if the spectral filter has two or more flanks. Alternatively, for example, a generally comparatively narrow-band bandpass filter can therefore be used for the detection. The bandwidth of the bandpass filter is preferably of the order of magnitude of the width of the resonance of the reflection or transmission spectrum of the photonic crystal. There are various options for modulating the spectral filter to tune the edge.

In a further development of this embodiment, an angle at which the spectral filter is aligned relative to the beam direction of the light source can be set for modulation of the spectral filter. In this case, the spectral filter can be an interference filter, for example. Alternatively, the spectral filter that can be modulated can also be implemented, for example, on the basis of an acousto-optical modulator or a combination of diffraction gratings and a liquid crystal modulator. The spectral filter, which is used to filter the light reflected or transmitted on the surface of the photonic crystal, can be designed accordingly.

In a further embodiment, the light source is a tunable laser. In this case, the intensity spectrum of the light source has a maximum intensity at the laser wavelength and two flanks falling steeply from the maximum intensity at shorter and longer wavelengths than the laser wavelength. By tuning the laser wavelength, which is carried out in a manner known per se for the laser, both flanks of the spectrum of the laser are spectrally shifted. In this case, the laser wavelength or the range in which the tuning of the laser wavelength is possible is matched to the range of the resonance of the photonic crystal.

In a further embodiment of the above device, a first linear polarization filter is arranged in the beam path of the light radiated onto the surface of the photonic crystal, and a second linear polarization filter rotated by 90° with respect to the first linear polarization filter is arranged in the beam path of the light reflected or transmitted by the surface. The crossed linear polarization filters can be used to filter out scattered light on the one hand and reflected light on the other hand, which has not interacted with the modes of the photonic crystal.

In an alternative embodiment of the above device, a circular polarization filter is arranged in the common beam path of the light radiated onto the surface of the photonic crystal and the light reflected from the surface. Light that has not interacted with the modes of the photonic crystal can also be filtered out with the aid of a circular polarization filter.

In a further embodiment, the above device comprises a supply device for supplying a liquid to the surface of the photonic crystal, the substance to be detected being contained in the liquid. For the accumulation of the substance to be detected on the surface, it has proven to be advantageous if it is contained in a liquid. The feeding device can be designed that To lead liquid in the form of a liquid flow, for example in a chamber, over the surface of the photonic crystal and to remove it from the surface again.

However, it is also possible for the delivery device to be designed to deliver the liquid, e.g. in the form of a single drop of blood, to the surface without the liquid being removed from the surface again. In this case, the photonic crystal together with the delivery device forms a sensor unit which can be introduced into the device and which can be exchanged for another sensor unit as soon as the detection of the substance has been completed.

According to a further aspect, the above-mentioned object is also achieved by the method mentioned at the outset, which comprises the following additional steps: spectral tuning of at least one flank in the spectrum of the light radiated onto the surface in the resonance range of the photonic crystal or spectral filtering of the light in the detection range and of the light reflected or transmitted in the reference region of the surface of the photonic crystal with a filter spectrum that has at least one edge, and spectral tuning of this edge, and detecting the substance by comparing the first intensity signal measured during the tuning with the second intensity signal measured during the tuning intensity signal. With regard to the advantages achieved with the method, reference is made to the above explanations in relation to the device.

In a variant of this method, when comparing the intensity signals, the shift of an edge of the first intensity signal measured during the tuning relative to a corresponding edge of the second intensity signal measured during the tuning is determined. As has been described above, the spectral shift of the resonance when the substance accumulates in the detection area can be determined very precisely in this way.

In a development of this variant, a concentration of the substance is determined during detection, specifically by means of a relationship determined by calibration between the shift of the edge of the first intensity signal measured during the tuning relative to the corresponding edge of the second intensity signal measured during the tuning and the concentration of the substance to be detected. The relationship between the concentration of the substance and the displacement of the flank can be determined in the manner described above in connection with the device.

Further advantages of the invention result from the description and the drawing. Likewise, the features mentioned above and those detailed below can be used according to the invention individually or collectively in any combination. The embodiments shown and described are not to be understood as an exhaustive list, but rather have an exemplary character for the description of the invention.

• 1a,b,c schematische Darstellungen von drei Ausführungsbeispielen einer Vorrichtung, die einen photonischen Kristall mit einer Oberfläche zur Anlagerung von zu detektierenden Substanzen, eine Lichtquelle und einen Detektor aufweist,
• 2 eine Darstellung der Oberfläche des photonischen Kristalls von 1a,b mit funktionalisierten Detektionsbereichen und mit nicht funktionalisierten Referenzbereichen,
• 3a,b Darstellungen einer spektralen Verschiebung einer Resonanz des Reflexionsspektrums des photonischen Kristalls beim Anlagern einer Substanz an der Oberfläche sowie einer Flanke im Spektrum der Lichtquelle oder im Filterspektrum des Spektralfilters, die im Bereich der Resonanz spektral durchgestimmt wird, sowie
• 4a-c Darstellungen eines ersten und eines zweiten Intensitätssignals, die während der Durchstimmung der Flanke in einem Detektionsbereich und in einem der Referenzbereich der Oberfläche gemessen werden.

The invention is illustrated in the drawings and is explained in more detail using exemplary embodiments. It shows the:

• 1a,b , c schematic representations of three exemplary embodiments of a device which has a photonic crystal with a surface for the accumulation of substances to be detected, a light source and a detector,
• 2 a representation of the surface of the photonic crystal of 1a,b with functionalized detection areas and with non-functionalized reference areas,
• 3a,b Representations of a spectral shift of a resonance of the reflection spectrum of the photonic crystal when adding a substance to the surface as well as a flank in the spectrum of the light source or in the filter spectrum of the spectral filter, which is spectrally tuned in the resonance range, as well as
• 4a-c Representations of a first and a second intensity signal, which are measured during the sweeping of the edge in a detection area and in a reference area of the surface.

In the following description of the drawings, identical reference symbols are used for identical or functionally identical components.

1a,b , c show a device 1, which is designed for the detection of several different (eg biological) substances 2. The device 1 comprises a light source 3, which is designed to radiate light 4 onto a planar, structured surface 5a of a photonic crystal 5. In the example shown, the photonic crystal 5 has a periodic structure on the surface 5a. The light source 3 includes collimating optics, not shown, in order to collimate the light 4 from the light source 3 and to direct it along a beam direction onto the surface 5a of the irradiate photonic crystal 5, which in 1a,b runs horizontally.

The radiated light 4 passes through the volume of the photonic crystal 5 and part of the radiated light 4 interacts with the structured surface 5a of the photonic crystal 5, with a proportion of the light being reflected. The reflected light 4a impinges on a detector which, in the example shown, is designed as a spatially resolving detector, more precisely as a camera 6 . An optical system that is not illustrated, which can be a telecentric optical system, for example, images the surface 5a of the photonic crystal 5 onto a detector surface of the camera 6 . An evaluation device 7 has a signal connection with the camera 6 in order to evaluate the images recorded by the camera 6, as will be described in more detail below.

At the in 1a,b Devices 1 shown, the incident light 4 is aligned perpendicular to the surface 5a of the photonic crystal 5. The detected reflected light 4a is also aligned perpendicular to the surface 5a of the photonic crystal 5 in this device. In order to separate the beam path of the light 4 radiated onto the surface 5a of the photonic crystal 5 from the beam path of the reflected light 4a, the devices 1 of FIG 1a,b each have a beam splitter 8, which is designed as a beam splitter cube in the example shown. In the event that the light 4 is irradiated obliquely, ie at an angle deviating from 90°, onto the surface 5a of the photonic crystal 5, the beam splitter 8 can be used to separate the beam path of the incident light 4 and the beam path of the reflected light 4a usually be dispensed with. The angle of incidence at which the incident light 4 strikes the surface 5a of the photonic crystal 5 can deviate from the angle at which the light 4a reflected on the surface 5a is detected by the camera 6 .

At the in 1a,c In the devices 1 shown, a first linear polarization filter 9a is arranged in front of the beam splitter 8 in the beam path of the light 4 incident on the surface 5a of the photonic crystal 5 in order to linearly polarize the incident light 4 . A second linear polarization filter 9b is arranged in the beam path of the light 4a reflected from the surface 5a of the photonic crystal 5, the orientation of which is rotated by 90° with respect to the first linear polarization filter 9a. The second linear polarization filter 9b only transmits reflected light 4a whose polarization direction is rotated by 90° to the polarization direction of the light 4 linearly polarized at the first linear polarization filter 9a and radiated onto the surface 5a.

With the aid of the crossed linear polarizers 9a, 9b, incident light 4, which does not interact with the photonic crystal 5 and therefore retains its polarization direction, and scattered light can be suppressed. Thus, only light 4a reflected on the surface 5a reaches the detector 6, which light interacts with the photonic crystal 5 and thereby undergoes a rotation of its direction of polarization. In order to bring about the rotation of the polarization direction of the incident light 4, in 1a,b In the example shown, the structuring direction of the photonic crystal 5 forms an angle of 45° with the polarization direction of the linearly polarized light 4 radiated onto the surface 5a. Since the two mode groups TE and TM are also rotated by 45° to the direction of polarization in this case, both modes are excited and part of the reflected light 4a is polarized in such a way that it is transmitted by the second linear polarization filter 9b. A selection of this angle other than 45° is possible in principle, but generally leads to a poorer signal-to-noise ratio.

As an alternative to the linear polarization filters 9a,b, in 1b A circular polarization filter 9 is arranged in the device shown in the common beam path of the light 4 radiated onto the surface 5a of the photonic crystal 5 and the light 4a reflected from the surface 5a. The light 4 radiated onto the surface 5a of the photonic crystal 5 is circularly polarized by the circular polarization filter 9 . The light 4a reflected from the surface 5a of the photonic crystal 5 passes through the circular polarization filter 9 again before it hits the detector 6 . Light 4a reflected from the surface 5a of the photonic crystal 5, which has not interacted with the modes of the photonic crystal 5, changes its handedness due to the phase jump caused by reflection and is thus suppressed when passing through the circular polarization filter 9 again. Light 4a reflected from the surface 5a of the photonic crystal 5, which interacts with the modes of the photonic crystal 5, loses the property of circular polarization and is thus not suppressed if the filter and mode axes have a parallel component. the inside 1b The circular polarization filter 9 shown can also be used with the in 1a,c devices 1 shown can be used instead of the two linear polarization filters 9a,b. Accordingly, in the device 1 of 1b instead of the circular polarization filter 9, the two linear polarization filters 9a, b of 1a,c be used.

The device 1 of 1a,b , c also includes a supply device 10 for supplying a liquid 11 to the surface of the photonic crystal 5. In the example shown, the supply device 10 has a supply line 12 for supplying the liquid 11 to a chamber 13 which encloses the surface 5a of the photonic crystal 5. The liquid 11 is discharged from the chamber 13 via a discharge line 14 . In the example shown, the delivery device 10 is a microfluidic device.

In the example shown, the device 1 serves to detect substances 2 contained in the liquid 10 . The substances 2 can be dissolved or suspended in the liquid 10, for example. With the help of the 1a,b , c The device 1 shown can be used to detect a large number of different substances 2 in different types of liquids 11 . The substances 2 can in particular be biological substances.

In the example shown, the liquid 10 is human blood and the substances 2 to be detected are biological substances, more precisely biomarkers in the form of antibodies. The device 1 enables the detection or verification of antigens and/or antibodies in human blood and can therefore be used, for example, as proof of the presence of an infection, e.g. a viral infection, or an immune reaction.

For this verification, it is not absolutely necessary for the liquid 10, which is supplied to the surface 5a of the photonic crystal via the supply line 11, to be removed from the surface 5a again. The delivery device 10 can, for example, form a disposable sensor unit with the photonic crystal 5 and the chamber 12, which is introduced into the device 1 for the detection of the substance 2. After the detection, the sensor unit is exchanged for another sensor unit, as described in the article by Ms. S. Jahns et al. cited above. is described. The device 1 can of course also be used to detect other substances 2 that are contained in other liquids 11, for example to detect bacteria, antibodies, antigens, etc. in milk, blood plasma, or lymph, or impurities in water, etc It is also possible to detect crystallization on correspondingly functionalized detection areas (e.g. using crystallization nuclei).

In order to be able to detect a plurality of different substances 2 contained in the liquid 11 simultaneously, a plurality of detection areas 15 are formed on the surface 5a of the photonic crystal 5 . A respective detection area 15 is functionalized with biological/organic materials in a manner known per se. According to the lock and key principle, a suitable biological substance 2, e.g. an antibody, can dock to a respective functionalized detection area 15 of the surface 5a, which leads to a change in the refractive index in the immediate vicinity of the surface 5a of the photonic crystal 5 at the respective detection area 15 .

The surface 5a outside of the detection areas 15 is not functionalized, ie a respective substance 2 to be detected cannot dock onto the surface 5a outside of the functionalized detection areas 15 . In 2 ring-shaped reference areas 16 are shown, which surround a respective circular functionalized detection area 15 . The reference areas 16 are not functionalized and basically do not differ from the remaining surface 5a outside the detection areas 15. However, only reflected light 4a, which is reflected by the respective detection area 15 on the surface 5a of the photonic crystal 5, is used for the evaluation described below , and reflected light 4a, which is reflected by a respective reference area 16 on the surface 5a of the photonic crystal 5.

By arranging a respective reference area 16 and an associated detection area 15 next to one another, a position-dependent background drift, temperature drift or changes in position and angle of the sample (deformation), etc. can be eliminated. It is understood that the geometry of the 2 Functionalized detection areas 15 shown can deviate from a circular geometry. The geometry of the reference areas 16 can also differ from that in 2 deviate from the circular geometry shown. If necessary, a common reference area 16 can be used in the evaluation for two or more of the detection areas 15 .

In the following, the detection of a substance 2 attached to one of the detection areas 15 is explained with reference to FIG 3a,b and 4a-c described. The subsequently described detection of the substance 2 at one of the detection areas 15 can take place at the same time as other substances 2 at the other detection areas 15 on the surface 5a of the photonic crystal 5 . The detection areas 15 can be functionalized for the detection or for the detection of different substances 2, but it is also possible that two or more detection areas 15 are functionalized for the detection of one and the same substance 2.

As described above, the accumulation of the substance 2 on the detection area 15 results in a change in the refractive index in the vicinity of the surface 5a of the photonic crystal 5 . As also described above, the surface 5a of the photonic crystal 5 is structured and thus forms a system similar to the behavior of electrons in the semiconductor for photons. In a known manner, the structuring of the photonic crystal 5 generates a reflection spectrum with a wavelength-dependent reflectivity R, which has a resonance 17 (resonance peak), as is shown in 3a,b is shown. As a rule, the reflection spectrum of the photonic crystal 5 has more than one resonance 17, but only one resonance 17 is required for the evaluation described below, so that the representation of further resonances in the reflection spectrum of 3a,b was waived.

As in 3a,b can be seen, the resonance 17 in the functionalized detection area 15 has a first resonance wavelength λ _D , while the same resonance 17 in the reference area 15 has a second resonance wavelength λ _R , which differs from the first resonance wavelength λ _D . The spectral shift Δλ=λ _D -λ _R of the resonance 17 in the detection area 15 relative to the reference area 16 is due to the change in refractive index when the substance 2 is attached to the surface 5a in the detection area 15 . Since the substance 2 does not accumulate in the reference region 16, the substance 2 accumulated in the detection region 15 can be detected using the spectral shift Δλ.

In order to measure the spectral shift Δλ or a measure of the spectral shift Δλ, in 1a,c Device 1 shown, the spectrum of light source 3 has a wavelength-dependent intensity I with two flanks 18a,b, while in 1b Device 1 shown, the spectral filter 20 has a filter spectrum with a wavelength-dependent transmission T with two flanks 18a,b, the flanks 18a,b being spectrally tunable in the region of the resonance 17 of the photonic crystal 5. The flanks 18a, b are at the in 3a,b shown example in the range of resonance 17 tunable in a wavelength interval between a minimum wavelength λ _MIN and a maximum wavelength λ _MAX .

The minimum wavelength λ _MIN is slightly smaller than the second resonance wavelength λ _R of the resonance 17 in the reference area 16. The maximum wavelength λ _MAX is slightly larger than the largest possible first resonance wavelength λ _D in the detection area 15. The largest possible first resonance wavelength λ _MAX is achieved , when the substance 2 has accumulated at all available places in the functionalized detection area 15, ie when the saturation of the functionalized detection area 15 with the substance 2 is reached. The wavelength interval λ _MAX -λ _MIN in which the edge 18a,b of the intensity I of the light source 3 or the edge 18a,b of the filter spectrum of the spectral filter 20 can be tuned can be of the order of approximately 10 nm, for example.

In the 1a Device 1 shown differs from that in 1c shown device by the way in which the tuning of the edge 18 of the spectrum of the light source 3 is generated. In the 1a The light source 3 shown has a broadband primary light source 19 in the form of a white-light LED and a spectral filter 20, which has the 3a Flanks 18a, b shown in the spectrum of the primary light source 19 are generated. In the example shown, the spectral filter 20 is a narrow-band bandpass filter with a high edge steepness. The spectral filter 20 can be modulated in order to spectrally tune the flanks 18a,b in the region of the resonance 17 of the photonic crystal 5.

At the in 1a In the example shown, the light source 3 has an actuator 21 for modulating the spectral filter 20, which makes it possible to set an angle α at which the spectral filter 20 is aligned with the beam direction of the light source 3. At the in 1a In the example shown, the spectral filter 20 can be tilted by an angle α of +/-10° starting from a basic position in which the spectral filter 20 is aligned perpendicular to the beam direction of the collimated light 4 of the light source 3 . The spectral filter 20 is a suitably designed interference filter. Instead of a spectral filter 20 in the form of a bandpass filter, another type of spectral filter can also be used, for example an edge filter, which has only a single edge instead of the two edges 18a,b.

In the 1b The device shown differs from that in 1a shown device is that the spectrum of the light source 3 is broadband and that the reflected light 4a, before it hits the detector 6, the modulated spectral filter 20 passes. The modulation of the spectral filter is done here as in the description of 1a specified.

The light source of the in 1c Device 1 shown is designed as a tunable laser 3 . The tunable laser 3 has a narrow-band spectrum with two flanks 18a, b that fall steeply, starting from a laser wavelength λ _L . In the spectral tuning of the Laser wavelength λ _L , the flanks 18a, b of the spectrum in the area of resonance 17 are also spectrally tuned, as is shown in 3b is indicated by an arrow.

For the measurement described below it is favorable in all three cases if the flank or flanks 18a,b in the spectrum of the light source 3 or in the filter spectrum, which is/are spectrally tuned in the range of the resonance 17, are as steep as possible.

4a-c each show a first intensity signal I _D and a second intensity signal I _R , which are measured while the flanks 18a, b of the spectrum of the light source 3 are being tuned. The first intensity signal I _D is calculated from the intensities of the pixels of the image of the detection area 15 on the detector surface of the camera 6, for example by averaging. Correspondingly, the second intensity signal I _R is calculated from the intensities of the pixels of the image of the reference area 16 on the detector surface of the camera 6, again for example by averaging. In 4a-c are the two intensity signals I _D , I _R for different settings of the angle α when tuning the spectral filter 20 in the form of the bandpass filter of 1a shown. Instead of averaging, another suitable calculation, e.g. a weighted averaging, of the intensities of the pixels of the image of the detection area 15 to calculate the first intensity signal I _D or of the pixels of the image of the reference area 16 to the calculation of the second intensity signal I _R can be used .

In the representation of 4a the number indicated on the abscissa corresponds to the number of a respective picture taken by the camera. The camera 6 can be designed, for example, to record a number of approximately 100 images per second at constant time intervals.

In 4b,c the intensity signals I _D , I _R are plotted against the wavelength λ. Such a plot is possible since there is a clear relationship between the respective angular position of the spectral filter 20 or the associated recorded image and the wavelength λ. It goes without saying that instead of numbering the recorded images or the wavelength λ, the intensity signals _{ID, I R can} also be plotted over time or over another suitable variable.

When displaying 4a the intensity signals I _D , I _R are shown when the spectral filter 20 is tuned over the entire adjustable variation range of the angle α from -10° to +10°, the image with the number zero in 4a corresponds to the angular position of -10° and the image with the number 600 corresponds to the angular position of +10°. When the spectral filter 20 is rotated from the basic position (at α=0°), the wavelength of the tuned edge 18a,b decreases in both directions, which is why the in 4a shown, which is essentially symmetrical to the basic position (the picture with the number 300). The left part of the representation of 4a up to the basic position thus corresponds to the tuning of the edge 18a,b from the minimum wavelength λ _MIN to the maximum wavelength λ _MAX in the basic position. The right part of the representation of starting from the basic position 4a corresponds to the tuning of the edge 18a,b from the maximum wavelength λ _MAX to the minimum wavelength λ _MIN .

As in 4a can be seen, the first intensity signal I _D is due to the spectral shift of the in 3a The resonance 17 shown is shifted during the accumulation of the substance 2 in the detection region 15 in comparison to the second intensity signal I _R , since when the spectral filter 20 is tuned from smaller to larger wavelengths, the resonance 17 initially occurs at the second resonance wavelength λ _R and at a later point in time the resonance 17 is swept over by the flanks 18a, b at the first resonance wavelength λ _R shifted by the spectral offset Δλ. Based on a comparison between the first and the second intensity signal I _D , I _R , the spectral offset Δλ can therefore be determined and the accumulation of the substance 2 can be detected based on the magnitude of the spectral offset Δλ.

The comparison between the two intensity signals I _D , I _R is preferably carried out in an intensity range in which they have the steepest possible rise. At the in 4b,c In the example shown, the comparison takes place at a steeply rising edge 22 of the first intensity signal I _D and at a corresponding, steeply rising edge 22' of the second intensity signal I _R . The relative displacement Δλ of the edge 22 in the first intensity signal I _D to the corresponding edge 22' in the second intensity signal I _R is determined in the example shown by using the distance in the values of the arguments of the intensity signals I _D I _R which corresponds to a certain proportion of the correspond to saturation or maximum values of the intensity signals I _D , I _R . The maximum values of the intensity signals I _D , I _R were 4a-c each normalized to one.

At the in 4c In the example shown, the shift Δλ between the two flanks 22, 22' is determined at an intensity value which corresponds to a proportion of 80% of the maximum intensities of the two intensity signals I _D , I _R . it understands It turns out that the shift Δλ can also be determined for a different proportion of the maximum intensities of the two intensity signals I _D , I _R , for example at 60% or at 40% of the maximum intensities. If necessary, to determine the shift Δλ, a mean value can also be formed from a plurality of values for the shift Δλ determined for different portions of the maximum intensities. It goes without saying that the relative displacement of the flanks 22, 22' can also be determined in another way, for example by using the distance between two straight lines which are fitted to the respective flank 22, 22'.

The accumulation of the substance 2 to be detected in the detection area 15 can be detected on the basis of the shift Δλ. For this purpose, the course over time of the amount of the shift Δλ can be observed during repeated, continuous tuning of the spectral filter 20 and the accumulation of the substance 2 to be detected can be recognized from an increase in the amount of the shift Δλ. The accumulation of the substance 2 on the detection area 15 can also be detected by comparing the amount of the shift Δλ with a predetermined threshold value and inferring the accumulation of the substance 2 when the threshold value is exceeded.

It is also possible to use the evaluation device 7 to determine the concentration of the substance 2 to be detected in the liquid 11 . For this purpose, the value of the displacement Δλ between the two flanks 22, 22', determined in the manner described above, is related to the concentration of the substance 2 in the liquid 11 using a relationship determined by calibration. The calibration can be carried out, for example, by bringing the same liquid 11 with different concentrations of the substance 2 to be detected into contact with the surface 5a of the photonic crystal and determining the value of the shift Δλ between the two flanks 22, 22'. In this case, the concentration of the substance 2 in the liquid 11 is determined with the aid of another suitable measuring setup. In this way, a calibration curve can be recorded, which enables the concentration of the substance 2 deposited in the liquid 11 to be measured.

Alternatively to the one associated with 1a,b described device 1, in which the light 4a reflected on the surface 5a of the photonic crystal 5 is measured by the detector 6, it is also possible to measure the light transmitted from the surface 5a of the photonic crystal 5 for the detection of the substance 2. This simplifies the structure of the device 1 since the light source 3, the photonic crystal 5 and the detector 6 can be arranged along a rectilinear optical bench. In this case, however, the light transmitted from the surface 5a passes through the liquid 11 before it strikes the detector 6. It is therefore generally necessary for the liquid to be essentially transparent to the light transmitted by the photonic crystal 5 .

QUOTES INCLUDED IN DESCRIPTION

This list of documents cited by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Patent Literature Cited

• WO 2011/091781 A1 [0005, 0006, 0011]

Claims (12)

Device (1) for the detection of at least one substance (2), comprising: - a photonic crystal (5) with a surface (5a) which has at least one detection area (15) and at least one reference area (16), wherein in the detection area ( 15) the substance (2) to be detected can be accumulated and the substance (2) to be detected cannot be accumulated in the reference region (16), with the accumulation of the substance (2) to be detected causing a resonance (17) in the transmission and /or spectrally shifts the reflection spectrum of the photonic crystal (5) in the detection area (15) relative to the reference area (16), - a light source (3) for radiating light (4) onto the surface (5a) of the photonic crystal (5) , - a detector (6) for measuring a first intensity signal ( _ID ) of the light (4a) reflected or transmitted in the detection region (15) of the surface (5a) of the photonic crystal (5) and for measuring a second inte nity signal (I _R ) of the light (4a) reflected or transmitted in the reference region (16) of the surface (5) of the photonic crystal (I _R ), characterized in that the light source (3) has at least one edge (18a, b) which can be tuned spectrally in the range of resonance (17) of the photonic crystal (5), or that the light source (3) is broadband and the device (1) has a spectral filter (20) that can be modulated for filtering the light in the detection range ( 15) and of the light (4a) reflected or transmitted in the reference area (16) of the surface (5a) of the photonic crystal (5), the filter spectrum of the spectral filter (20) having at least one flank (18a, b) which area the resonance (17) of the photonic crystal (5) can be spectrally tuned, and that the device (1) has an evaluation device (7) which is designed by means of a comparison of the first measured during the tuning Intensity signal (I _D ) to detect the substance (2) with the second intensity signal (I _R ) measured during the tuning. device after claim 1 , characterized in that the evaluation device (7) is designed, when comparing the intensity _{signals (ID, I R )} , a shift (Δλ) of an edge (22) of the first intensity signal (ID) measured during _tuning relative to a corresponding edge (22') of the second intensity signal (I _R ) measured during the tuning. device after claim 1 or 2 , characterized in that the evaluation device (7) is designed to determine the concentration of the substance (2) to be detected by means of a relationship determined by calibration between the shift (Δλ) of the edge (22) of the first intensity signal ( measured during tuning) I _D ) relative to the corresponding flank (22') of the second intensity signal (I _R ) measured during the tuning and the concentration of the substance (2) to be detected. Device according to one of the preceding claims, in which the light source (3) comprises a broadband primary light source (19) and a spectral filter (20), preferably an edge filter or a bandpass filter, which covers the edge (18a, b) in the spectrum of the light source (3 ) generated, wherein the spectral filter (20) can be modulated in order to spectrally tune the flank (18) in the spectrum of the light source (3) in the region of the resonance (17) of the photonic crystal (5). device after claim 4 , in which, for the modulation of the spectral filter (20), an angle (α), at which the spectral filter (20) is aligned relative to the beam direction of the light source (3), can be adjusted. Device according to one of Claims 1 until 3 , in which the light source is a tunable laser (3). Device according to one of the preceding claims, in which in the beam path of the light (4) radiated onto the surface (5a) of the photonic crystal (5) a first linear polarization filter (9a) and in the beam path of the light reflected or transmitted by the surface (5a). (4a) a second linear polarization filter (9b) rotated by 90° with respect to the first linear polarization filter (9a). Device according to one of Claims 1 until 6 , in which a circular polarization filter (9) is arranged in the common beam path of the light (4) radiated onto the surface (5a) of the photonic crystal (5) and the light (4a) reflected from the surface (5a) of the photonic crystal (5). is. Device according to one of the preceding claims, further comprising: a supply device (10) for supplying a liquid (11) to the surface (5a) of the photonic crystal (5), the substance (2) to be detected being contained in the liquid (11). is. Method for detecting at least one substance (2), comprising the steps: - Radiating light (4) onto a surface (5a) of a photonic crystal (5), the surface (5a) having at least one detection area (15) and at least one reference area (16), the substance (2) to be detected accumulates in the detection area (15) and does not accumulate in the reference area (16), and where the accumulation of the substance (2) to be detected causes a resonance (17) in the transmission and/or reflection spectrum of the photonic crystal (5) in the detection area (15 ) shifts spectrally relative to the reference area (16), - measuring a first intensity signal (ID) of the light (4a) reflected or transmitted in the detection area (15) of the surface ( _5a ) of the photonic crystal (5) and a second intensity signal (I _R ) of the light (4a) reflected or transmitted in the reference region (16) of the surface (5a) of the photonic crystal (5), characterized by the steps: - Spectral tuning at least ns a slope (18a, b) in the spectrum of the surface (5a) irradiated light (4) in the resonance (17) of the photonic crystal (5) or - spectral filtering in the detection area (15) and in the Reference area (16) of the surface (5a) of the photonic crystal (5) reflected or transmitted light (4a) with a filter spectrum that has at least one flank (18a, b), and spectral tuning of this flank (18a, b), and - detecting the substance (2) by comparing the first intensity signal (I _D ) measured during the tuning with the second intensity signal (I _R ) measured during the tuning. procedure after claim 10 , characterized in that when comparing the intensity signals (I _D , I _R ), the displacement of an edge (22) of the first intensity signal (I _D ) measured during the tuning relative to a corresponding edge (22') of the second intensity signal measured during the tuning (I _R ) is determined. procedure after claim 11 , characterized in that during detection a concentration of the substance (2) is determined by means of a relationship determined by calibration between the displacement of the edge (22) of the first intensity signal (I _D ) measured during tuning relative to the corresponding edge (22' ) of the second intensity signal (I _R ) measured during the tuning and the concentration of the substance (2) to be detected.

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