EP2564184A1

EP2564184A1 - Method and arrangement for detecting biological and/or chemical substances

Info

Publication number: EP2564184A1
Application number: EP11754274A
Authority: EP
Inventors: Andreas Fischer
Original assignee: Jenoptik Polymer Systems GmbH
Current assignee: Jenoptik Polymer Systems GmbH
Priority date: 2010-04-25
Filing date: 2011-04-25
Publication date: 2013-03-06
Also published as: DE112011101450A5; WO2011150905A4; DE102010018636A8; WO2011150905A1; DE102010018636A1

Abstract

The invention relates to a method and at least one arrangement for detecting biological and/or chemical substances. A light beam or a light bundle generated by a pumped light energy source with an excitation wavelength λ_Α is directed onto a carrier substrate, on which an optical function structure in the form of an organic luminous means is situated, on which in turn the substance(s) to be detected is/are deposited in a suitable form, such that the difference wavelength λ_ΔΑ or X_R produced as a result of absorption and changed diffraction optical properties is captured using a suitable receiver, and an evaluation unit that is coupled thereto is used to detect the substances on the basis of a data comparison system. The organic phosphor is preferably at least one organic distributed feedback laser (DFB laser). The method and a special arrangement can also be used to detect a specific substance using individual laser pixels (2P).

Description

[Patent application]

[Name of the invention]

Method and arrangement for the detection of biological and / or chemical substances

The present invention relates to a method and at least one associated arrangement for the detection of biological and / or chemical substances or analytes.

In these markerless tests and / or the detection of several substances, organic bulbs form an essential basis or component of these tests.

Biomedical practice is today unthinkable without laser technologies. This ranges from the

Laser-optical detection of analytes in the field of

medical diagnostics to laser medical applications of photodynamic in vitro therapy of cancer cells. The provision of the

For this required laser wavelengths in the area

from 400 to 700 nm, so far done by the

merging various conventional types of lasers (e.g., gas lasers, DPSS lasers, LDs). This inevitably requires a large amount of equipment,

is therefore expensive and presents a development barrier in the context of system integration and

miniaturization. Especially for the always

strong area of on-site diagnostics (eg mass screening influenza or

Proof of sepsis) are currently lacking suitable technologies that can be miniaturized, easily integrated

and are also inexpensive to produce with sufficient power spectrum. The need for simple,

multiplexed systems is thus very large. This

especially for lab-on-chip systems the point of-care diagnostics, for compact bioreader systems

and for pharmacological screening in the context of

photodynamic cancer cell therapy. The use of test strips as a one-time test for the detection of biological and chemical components has become established on the market, in particular in analytics and medical technology. So far, however, such tests can only be used for individual substances, which is due to the use of special markers and their storage on a substrate in a suitable form.

The marker substances themselves must be prepared in complex processes and are not or difficult to handle without an additional substrate carrier. In addition, the test strips consisting of substrate and markers have a limited service life and can only be produced in large quantities with great technical effort.

The object of the invention is therefore to provide a method and corresponding arrangements for the detection of analytes, which can detect several substances that does not require any marker substances and at the same time eliminates or at least reduces the disadvantages mentioned. The object of the invention is achieved by a photometrically acting method which can detect a plurality of substances in broadband use.

In the method according to the invention, a light beam or a light bundle having an excitation wavelength λ _{Α is} produced successively from a light source, preferably a pumped light energy source, which light beam is directed directly or laterally in a suitable manner onto a carrier substrate,

on which there is an optical functional structure in the form of an organic light source, on which in turn the to Detecting substance is applied in a suitable form and the changes in the result of the absorption diffractive optical

Characteristics generated difference wavelength λ _Δ Α detected by a suitable receiver and a coupled evaluation unit based on a data comparison system

Detection of substances is made.

As a pumped light energy source (s) preferably pump lasers or pump LEDs are used, which are used individually or also in

Combination can be used. If several pumped light energy sources are used, their arrangement depends on a suitable structural design and size of the carrier substrate and the analytes to be examined.

The carrier substrate used is preferably a suitable polymer substrate.

In a particular embodiment of the invention, an optical functional structure of an organic light source, which preferably carries lattice structures, is located on the carrier substrate. In combination of the material properties and suitable diffraction structures at the surface or in the volume of the materials results in a lasing effect.

In an advantageous embodiment of the invention, an organic distributed feedback laser (DFB laser) is used as the organic light source. Fig. 1 shows the basic method of detection and an arrangement, which is also the subject of the invention. It is understood that this

Embodiment does not include a final complete variant of the invention, but that equivalent-acting and equivalent arrangements are included within the scope of protection. Organic light-emitting devices which are suitable in a suitable manner are also those organic electronic components, for example in the form of organic electroluminescent devices (OLEDs). However, it is also possible in particular further and unspecified embodiments of the invention to use organic integrated circuits (I-ICs), organic field-effect transistors (O-FETs), organic thin-film transistors (O-TFTs), organic light-emitting transistors (O-LETs), organic solar cells (O-SCs), organic optical detectors, organic photoreceptors sensors, organic field quench devices (O-FQDs), light-emitting electrochemical cells (LECs), organic laser diodes (O-lasers) or so-called organic plasmon-emitting devices.

In Fig. 1 is located on a carrier substrate (2) has an optical functional structure in the form of a DFB laser (3).

Will a biological substance (4), preferably in aqueous solution, in direct contact with the surface of the DFB laser

(3), this is partially absorbed by the DFB laser. As a result of the absorption results in a change in the diffractive properties of the material.

If an excitation of the DFB laser now takes place, preferably with a pump laser or a pump LED (1) with the excitation wavelength λ A, the change in the diffraction properties caused by the absorbed materials leaves a determination on the composition of the biological substance

(4) too.

In the exemplary embodiment, the evaluation is spectrally optical with a spectrometer (5) or it can also be made single-sensitive with a special photodetector with filter function (5). In a suitable evaluation unit (6), the comparison of the spectral fingerprints with a database takes place.

At the end of the investigation, in this embodiment, a digital statement is made about the presence of a specifically sought-after biological substance as part of the aqueous solution.

The particular advantages of using organic DFB lasers are based in particular on the surface and volume lattice structure. We are talking about thin Layer or ikrolasern with adjustable wavelength, which can be integrated into the disposable tests.

Organic substances react with liquids physically or chemically by absorbing the liquids into their own material. As a result, the physical or chemical properties of the bulbs change. Will now the

Raw state defined as a reference for measurement after the liquid intake, can be a change in the optical

Measure the properties of the lamps (refractive index etc.). This change in properties is directly related to the concentration of the elements / substances to be detected dissolved in the liquid. In an advantageous manner, the concentration of the elements / substances can thus be technically determined by known optical / photometric methods

(Spectrometer, photometer, etc).

The invention also relates to at least one arrangement for the detection of biological and / or chemical substances, which is characterized in that it consists successively of at least one pumped light energy source which the generated light beam or light beam with an excitation wavelength λ _Α so on her Can direct carrier substrate on which there is an optical functional structure in the form of an organic light source, on the turn to be detected / n substance / s can be applied in a suitable form,

and that for detecting the diffraction-optical properties produced as a result of the absorption, the difference wavelength / n λ _Δ Ä or λ _{R is arranged} downstream of a receiver unit,

which in turn is coupled to an evaluation unit with an integrated data comparison system for the detection of the substances. 2 shows a further embodiment and embodiment of the invention, which illustrates the advantageous arrangement of a plurality of DFB laser pixels (2P) to a DFB laser array (3A).

Conventionally, the optical detection of individual substances based on multispectral sensitive receiver systems. In this case, a significant amount of time is generated by comparing the recorded signals with stored in a database signal characteristics. The arrangement shown in the embodiment 2 simplifies the evaluation and reduces the time required, especially in a method in which the search for a concrete substance is in the center.

In this case, the inventive physical action principle has already been described above and explained in the embodiment 1. In a special embodiment, the pumped light energy source (1) can also be a combination of a plurality of pump lasers or pump LEDs tuned to the laser array, which can be used independently of one another in terms of time and wavelength.

However, the laser array (3A) can now be polled wavelength-specifically, i. individual laser pixels (2P) are excited separately and emit light of different wavelengths.

By excitation of several laser pixels (2P) simultaneously or individually or selectively, the wavelengths (λ i, λ 2, λ n + 1 ...) add up to a resultant Ä _R from which the required information about the substance sought (available yes / no, if yes on which array, etc.) is won.

Thus, in a particular mode of operation of the invention, a specific substance (sample X, x, Y, y ....) can be searched for concretely. In a further application of the invention, such organic laser arrays can be adapted and flexible

Use source of excitation for bioreader (ie device technology), if the detection can not be carried out without marker due to low concentrations.

Previous systems are based on the specific interaction between marker and biomolecule on the one hand and specific, highly sensitive fluorescence detection on the other hand.

In the marker-free test according to the invention, the lasing signal simultaneously serves as a biosensitive parameter. (Intensity and / or wavelength). Advantageous embodiments, in particular for increasing the sensitivity of the system, result, for example, from

the DFB structure, i. Period and amplitude of the grating, thickness of the gain medium or refractive index

This is an optical conversion of molecular

Events in a macroscopic change of the grating or the optical parameters. An improvement of the diffraction phenomena and the sensitivity of the system can thus be made.

Examples are variation by mechanical upsetting or stretching, or by electro-actuation of elastomers or sources by the solution to be detected,

or

b) - Modification of the organic bulbs on gain medium (deletion, different wavelength).

A porous layer constitutes the gain medium which receives or carries a biosensitive laser dye (particularly suitably a "laser dye with biological anchor group"), thus making the laser dye a biomarker. or

c) - Amplification mechanisms via plasmonic effects

Amplification effects can be achieved by plasmon resonance, based on built-in nanoparticles oscillating under light, so that even low concentrations can be detected.

The aim of the invention is also suitable solutions

find, in particular, multispectral applications

enable. For this purpose, according to the invention, laser arrays, as already described, are suitable based on

organic thin film laser structures used in

existing microsystem technologies are integrated into Lab-on-Chip (LOCS) systems. Furthermore

These are flexible in the application specific

Performance adjustment and allow a cost-effective

Mass production as a disposable article.

In addition to the invention, it should be mentioned that the required

Pump energy to the individual thin-film lasers via optical waveguide or according to conventional optical deflection units is supplied. With suitable light sources, such as laser and / or LED, all integrated thin-film lasers can be supplied with pump energy simultaneously via a small and inexpensive external laser module or LED module.

The individual laser elements are optimized to achieve the application-specific laser properties within the integrated array. This technology can be transferred directly to lab-on-chip technologies.

As already described for FIG. 1, for example, a pump laser (UV light) of an excitation wavelength λ A irradiates a polymer substrate on which, as a further embodiment of the invention, an organic surface lattice is enriched or enriched with nanoparticles the surface of which is suitably nanoparticles that contribute to the reinforcement.

On it is or the biological samples or are. The concentration of the biological sample (s) present in a generally suitable solution changes / changes the optical properties of the optically active organic light sources (polymer lattice and surface lattice).

The difference wavelengths as resultant λ _R (wavelength shift, intensity shift) is detected by means of a suitable receiver, eg a spectrometer, and calculated and compared with the aid of a suitable evaluation system or an evaluation unit, eg a PC with database acquisition and / or an evaluation software. The result gives an indication of the specific biological samples and can thus be used quickly and safely.

It is understood that arrangements with equivalent-acting elements in the context of the invention are to be regarded as included therein.

[REFERENCE LIST]

pump laser

Polymer substrate as a carrier substrate DFB laser pixel

Organic surface grid of an organic

light bulb

(e.g., azobenzene or the like, possibly with

nanoparticles)

DFB laser array

Biological sample / n (X; x; Y; y)

The concentration of the solution present in the solution

biological sample (s) changes the optical

Properties of the optically active organic light emitting means (polymer substrate + surface lattice)

Receiver unit (e.g., spectrometer)

Evaluation unit (for example PC + database)

Claims

[Claims]

1. A method for the detection of biological and / or chemical substances, characterized in that a generated from a pumped light energy source light beam or a light beam with an excitation wavelength λ _Α is directed onto a carrier substrate on which an optical

Functional structure is in the form of an organic light source,

on which in turn the substance / s to be detected is applied in a suitable form,

such that the difference wavelength λ _Δ A or A _R produced as a result of the absorption changing diffractive optical properties is detected by means of a suitable receiver

and via an evaluation unit coupled thereto based on a data comparison system, the detection of the substances is carried out.

2. The method according to claim 1, characterized in that at least one pump laser and / or at least one pump LED are used as the pumped light energy source.

3. The method according to claim 1 and 2, characterized in that organic light-emitting means are used with an optical functional structure, which preferably have lattice structures.

4. The method according to claim 1 to 3, characterized in that as an organic light bulbs organic electroluminescent zenzvorrichtungen (OLEDs) or organic integrated circuits (I-ICs), organic field effect transistors (0-FETs), organic thin-film transistors (O- TFTs), organic light-emitting transistors (0-LETs), organic solar cells (O-SCs), organic optical detectors, organic photoreceptors zeptors, organic field quench devices (O-FQDs), light-emitting electrochemical cells (LECs), organic laser diodes (O-lasers) or so-called organic plasmon-emitting devices, or in particular at least one organic distributed feedback laser (DFB). Laser) can be used.

6. The method according to at least one of the preceding claims, characterized

that thin-film or ikrolaser with adjustable wavelengths are used as organic lamps.

7. The method according to at least one of the preceding claims, characterized in that a plurality of DFB laser pixels (2P) to a DFB laser array (3A) are used as organic lamps.

8. The method according to claim 7, characterized in that for the detection of a particular substance individual laser pixels (2P) are excited separately, which in turn emit light of different wavelengths and / or

by the excitation of a plurality of laser pixels (2P) simultaneously or individually or punctually, the information about the substance sought is obtained from the resulting wavelength λ _κ .

9. The method according to at least one of the preceding claims, characterized in that the organic light-emitting means is modified with a medium which can absorb and carry a biosensitive laser dye as a porous layer.

10. The method according to at least one of the preceding claims, characterized in that the organic light source is enriched with nanoparticles.

11. The method according to at least one of the preceding claims, characterized in that

an optical conversion of molecular events into a macroscopic change of the grating to improve the diffraction phenomena and the sensitivity of the system is made.

12. Arrangement for the detection of biological and / or chemical substances, characterized in that it consists successively of at least one pumped light energy source, which can direct the generated light beam or light beam with an excitation wavelength λ _Α on a carrier substrate associated therewith, on the there is an optical functional structure in the form of an organic luminous means,

on the substance / s to be detected in turn can be applied in a suitable form,

and that a differential unit wavelength / n λ _Δ Α or λ _R, which is generated as a result of the absorption and which is modified as a result of the absorption, is arranged downstream of a receiver unit,

which in turn is coupled to an evaluation unit with an integrated data comparison system for the detection of the substances.

13. Arrangement for the detection of biological and / or chemical substances according to claim 12, characterized in that the pumped light energy source comprises at least one pump laser and / or at least one pump LED.

14. Arrangement for the detection of biological and / or chemical substances according to claim 12, characterized in that the organic light-emitting devices are organic electroluminescent devices (OLEDs) or organic integrated circuit devices. (I-ICs), organic field-effect transistors (O-FETs), organic thin-film transistors (O-TFTs), organic light-emitting transistors (O-LETs), organic solar cells (O-SCs), organic optical detectors, organic photors - zeptors, organic field quench devices (0-FQDs), light-emitting electrochemical cells (LECs), organic laser diodes (O-lasers) or so-called organic plasmon-emitting devices or in particular at least one organic distributed feedback laser (DFB Laser) are.

15. Arrangement according to at least one of the preceding claims, characterized in that the organic light-emitting means consist of a DFB laser array (3A) with a plurality of DFB laser pixels (2P).