Optics: measuring and testing – Sample – specimen – or standard holder or support
Reexamination Certificate
1998-03-16
2002-10-22
Pham, Hoa Q. (Department: 2877)
Optics: measuring and testing
Sample, specimen, or standard holder or support
C356S246000, C356S328000, C422S082110, C422S082050, C385S012000
Reexamination Certificate
active
06469785
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to an optical detection device, especially for chemical analyses of small-volume samples, comprising at least one light source for emitting detection light, at least one photoelectric detection unit for detecting a light intensity and converting the light intensity into a corresponding electrical signal, at least one measuring cell for holding a sample to be examined, and one or more optical paths coupled to the at least one measuring cell being formed between the light source(s) and the photoelectric detection unit(s).
It has long been known to carry out qualitative and quantitative chemical analyses of samples by optical means. Examples of such optical measuring methods are electrophoresis and chromatography. In such an optical examination of a sample, detection light emitted by a light source impinges on the sample located in a measuring cell. The light leaving the measuring cell is detected by a photoelectric detection device. When the detection light interacts with the sample, or rather with an analyte contained in the sample, given a suitable absorption spectrum of the analyte, absorption of the detection light can occur and, if the analyte is capable of luminescence, for example as a result of having been suitably prepared with a fluorescence marker, the absorbed detection light can be emitted again by the analyte in the form of luminescence.
For modern biochemical diagnostics there is a general trend towards miniaturization of such optical detection devices so that the use of as small a quantity of sample as possible suffices. Furthermore, in medicine and biochemistry, samples are often examined in respect of several different analytes, so that it is necessary in the course of a rapid processing operation to examine qualitatively, and, where applicable, quantitatively, as far as possible all of the analytes simultaneously.
To examine a sample in respect of various analytes it is known, for example, to bring the sample into contact with a corresponding number of sensor layers, the sensor layers being selectively provided with chemical or biochemical recognition elements immobilized in the sensor layer. The recognition elements each comprise specific affinity partners of the relevant analyte to be detected.
For the optical detection of a specific analyte in the sample it is known, for example, to label the analyte to be detected, which will be captured by the recognition element sensitive thereto which is immobilized on the sensor layer, using a luminescent dye and to detect optically as a measured variable the luminescence radiation or the change in the luminescence radiation of the detection layer resulting from the contact between the analyte and the recognition element.
In the case of optical sensor devices, it is often possible to use the evanescent luminescence excitation method. In that method, excitation light is coupled into a waveguide surrounded by media of lower refractive index. The excitation light is guided in the waveguide by total reflection at the transition between the media having differing refractive indexes. However, in the total reflection, the excitation light enters a short distance into the adjacent medium, with an exponential reduction in its intensity, where it produces the so-called evanescent field. Using the evanescent light intensity, a sample directly adjacent to the optical waveguide can be excited to emit fluorescence. The sensor layer which is provided with the immobilized recognition elements and over which the flowable sample is passed is arranged on the optical waveguide. In such optical sensor devices, the optical waveguide is advantageously in the form of a planar optical waveguide. A planar optical waveguide of that kind on the one hand may be an integral component of a flow cell and serve, for example, as a cover plate for the flow channel and, on the other hand, it can be manufactured simply, and in a manner suitable for mass production, by known deposition methods.
If a large number of analytes is to be examined, it is expedient to arrange the individual biochemical sensor elements in an array. A light source and at least one light detection device are associated in each case with that array of sensor elements. In order to meet the requirements for a small design of the optical detection device, recourse is therefore had to individual edge-emitting semiconductor lasers and conventional semiconductor photodetectors. Such a device comprises, for example, an array of edge-emitting semi conductor lasers mounted on the surface of a substrate, the emission light of which is coupled into respective associated waveguides. The waveguides, which form the interaction zone with the sample, are in contact with the sensor layers provided with recognition elements specific for the relevant analytes. After passing along the interaction zone, the light can be guided via coupling-out devices onto the detection surface of respectively associated semiconductor photodetectors.
The edge-emitting semiconductor lasers are not as a rule, however, produced on the same substrate as the semiconductor photodetectors. Since edge-emitting semiconductor lasers according to conventional production technology emit light parallel to the surface of the substrate, it is necessary either to expose a side edge of a laser element inside the substrate, for example by etching a trench, and guide the emitted light out of the depths of the substrate via deflectors, or to remove the laser unit from the substrate. Since the deflectors in question can be produced only with great difficulty, edge-emitting semiconductor laser elements are usually removed from the substrate and mounted in the desired emission direction on the foreign substrate containing the semiconductor photodetectors. Despite these considerable limitations resulting from the high number of, in some cases, non-automatable operations in the manufacturing of such detector arrangements, in comparison with other laser systems, such as helium-neon lasers, edge-emitting lasers are unrivalled in terms of the space they require and also in their efficiency in converting electrical energy into optical energy, which, in the case of edge-emitting semiconductor lasers, is considerably greater than that of, for example, a helium-neon laser.
However, those known devices have the disadvantage, that there are limits to the increasing miniaturization, inasmuch as, even using edge-emitting semiconductor lasers that have been separated from their mother substrate and applied to a foreign substrate, the surface area occupied by an edge-emitting semiconductor laser is typically 300×100 &mgr;m
2
. Owing to the need to separate the edge-emitting semiconductor laser from the mother substrate a and fasten it in a suitable orientation to a foreign substrate, the manufacturing process for an optical detection device according to the difficult and time-consuming and requires manual work, which adds considerably to the costs of the optical detection device.
The purpose of the invention, therefore, is to provide an optical detection device, especially for chemical multiple analyses, preferably of small-volume samples, that has a reduced minimum overall size and a simplified manufacturing process.
That problem is solved according to the invention in a first solution by an optical detection device of the kind previously mentioned that is further distinguished by the fact that each light source is a surface-emitting semiconductor laser.
The surface-emitting laser of the optical detection device according to the invention has, for example in current designs, a size of approximately 10×10 &mgr;m on the substrate, with the result that the surface area occupied can thereby be reduced by a factor of about 1:300 in comparison with a customary commercially semiconductor laser of the kind previously mentioned at the beginning. Furthermore, a surface-emitting laser has a lower power consumption since the threshold currents in that component are lower by about an order of magnitude than
Duveneck Gert Ludwig
Gulden Karlheinz
Kunz Rino Ernst
Söchtig Jürgen
Pham Hoa Q.
Wenderoth , Lind & Ponack, L.L.P.
Zeptosens AG
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