Optics: measuring and testing – By light interference
Reexamination Certificate
1998-02-13
2001-08-21
Kim, Robert (Department: 2877)
Optics: measuring and testing
By light interference
C356S513000
Reexamination Certificate
active
06278523
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the field of miniaturised optical sensors and more particularly sensors intended for the measurement of a fluorescent marker in small cavities, for example, the small bronchia, for the in vivo measurement of bronchial capillary permeability.
2. Description of the Related Art
The use of an interferometric heterodyne probe, integrated onto silicon, is known in the state of the technology of miniaturisable optical sensors, notably in biomedical applications.
The principle of heterodyne technology in interferometry is based on the modification of the optical frequency on one of the arms of the interferometer. The interference fringes can be modulated in phase and detected photo-electrically. The technique allows access to the phase of the phenomenon observed directly from the optical signal. In comparison with homodyning techniques, that link counting of fringes to methods of linear interpolation, heterodyne detection has two main advantages:
an improvement of the resolution linked to the phase extraction,
better tolerance of low frequency noise thanks to the shift of the useful signal far form external parasite signals.
The transposition of the massive architecture of heterodyne interferometry into a fibre version leads, in general, to a degradation of the signal to noise ratio, linked to external interference and parasitic reflections. In addition, “all fibre” shift devices are rare and one comes up against problems of coupling the massive phase modulators and the input of the fibre that seriously limit the applications that require miniaturisation of the probe.
Thanks to the optical technologies for integration onto silicon, the future is assured for micro-interferometers of very small size that can be manufactured by monolithic integration. The optical device integrated onto silicon is particularly well suited to “biomedical sensor” applications where a sensitive “superstrate” layer of hydrocarbon or polymer is deposited on the measurement arm of the interferometer (generally the Mach-Zehnder configuration). Some typical examples of biological and chemical sensors are described in the following documents:
“Integrated optical gas sensors using organically modified silicates as sensitive films”, Sensors and Actuators B, Vol. 11, (1993), pp. 361-374, 4. A. Brandenburg, R. Edelhauser, F. Hutter,
“Integrated optical sensors for halogenated and non-halogenated hydrocarbons”, Sensors for Actuators B, Vol. 11,(1993), pp. 207-212, G. Gauglitz, J. Ingenhoff,
“Influence of thin superstrate films on evanescent waves in surface waveguides”, Ber. Bunsenges. Phys. Chem, Vol. 11, (1991), pp. 1588-1563, G. Gauglitz, J. Ingenhoff,
“Integrated optical chemical and direct biochemical sensors”, Sensors and Actuators B, Vol. 29, (1995), pp. 37-50.
“Integrated optics with macro-flow cell”, Proc. SPIE, Vol. 1793, (1992), pp. 199-211, A. A. Boiarski, J. R. Busch, B. S. Bhullar, R. W. Ridgway, V. E. Wood.
If numerous integrated optical “bio-sensors” have appeared, they are based principally on homodyning technologies. The technique of integration of optical micro-probes comes up against the difficulty of producing a modulation of the reference beam necessary for heterodyning onto a silicon substrate that is playing a passive role.
SUMMARY OF THE INVENTION
This invention is aimed at remedying this disadvantage by proposing an original optical architecture, notably for a specific “biomedical sensor” application. This architecture opens up a new route of carrying out the heterodyning technique based on an “active” arrangement, provided thanks to the interaction between an optical beam being propagated in a monomodal silicon guide and a surface acoustic wave. The piezo-electric material required for the generation of acoustic waves is a thin layer of zinc oxide.
The invention is also aimed at a particular application for such a sensor for the in vivo assessment of the permeability of the capillary walls in the small bronchia. Neither a method nor a device exists in the prior art that permits the in vivo assessment of the permeability of the capillary walls in the small bronchia.
The invention responds to this need by a method and a device that allows the in situ measurement of a fluorescent marker by an interferometric sensor, integrated onto a silicon substrate. Such a micro-optical-electrical-mechanical device is capable of providing a miniature measurement tool in the medical field, that can operate remotely, in situ and in vivo.
The usefulness of concentrating the measurement on the small bronchia rather than on the air cells, that is to say of measuring, in vivo the bronchial capillary permeability is that it allows quantification of the inflammation essentially within bronchia of diameter between 0.5 and 3 mm. In effect, these bronchia are the seat of an oedema through an increase in the permeability of the capillary walls in numerous inflammatory pathologies including asthma. Two aspects of the bronchial capillary permeability can be studied: the permeability to liquids and the permeability of a fluorescent indicator. The current techniques only permit measurement of the permeability of the capillaries on an isolated bronchus. Hence the permeability to liquids is assessed form the lowering of concentration of a non-diffusible fluorescent indicator as a function of time, when a hyperosmolar liquid is introduced into the bronchial opening. For the permeability to solutes, the passage of an indicator perfused into the bronchial opening towards the bronchial epithelium is measured.
REFERENCES:
patent: 5465151 (1995-11-01), WyBourne et al.
patent: 5854868 (1998-12-01), Yoshimora et al.
Centre National de la Recherche Scientifique--CNRS
Kim Robert
Schnader Harrison Segal & Lewis LLP
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