Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals
Reexamination Certificate
1999-12-21
2001-04-03
Chin, Christopher L. (Department: 1641)
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
C156S922000, C156S922000, C422S051000, C422S051000, C422S082010, C422S082050, C422S082110, C427S002130, C427S496000, C427S551000, C427S569000, C427S576000, C427S578000, C427S579000, C427S421100, C435S004000, C435S287100, C435S287200, C436S524000, C436S525000, C436S805000
Reexamination Certificate
active
06210977
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention pertains to a process for producing a device for measuring or investigating physiological parameters in biological components (“biocomponents”). The device has at least one sensor having a measuring structure with an active contact surface for the biological components. In addition, the invention relates to a measuring device produced according to the process.
Biosensors continue to gain in importance with the very large number of cellular microsystems. The combination of a biological microsystem with a physical transducer permits the conversion of primary signal responses of the biological system into an electrical signal, which can then be registered and processed further without difficulty. Common to all sensors is that the primary sensory function of the system is assumed by a living cell or its components (e.g., receptors, gamma-globulins), and that their output signals are received by different, physical transducers.
It has become apparent in the development and testing of sensors that not all cell types or biocomponents can produce equally good contact with the transducer surfaces. To be sure, in many cases obtaining good adhesion for batch processes has succeeded through the choice of culture conditions. Nonetheless, the conditions for flow injection batches cannot be guaranteed for all cells or the like. In particular, such cells from animal cell lines which did not originally come from tumor cells are problematic in this respect. Furthermore, there is the difficulty with immune sensors on an FET basis that an optimal immobilization of the antibodies used requires an alignment of the reactive epitopes in order to receive a better signal response.
BRIEF SUMMARY OF THE INVENTION
The object of the present invention is to increase the mechanical anchoring of biocomponents (e.g., cells, receptors, gamma globulins) on the active contact surfaces of the sensors and further to improve the signal transmission properties and measurement sensitivity further.
For accomplishing this objective in accordance with the invention, it is proposed that the active contact surface of the sensor be structured approximately corresponding to the outer contours of the biocomponent in question. Through this structuring of the active contact surface, the biocomponents (e.g., cells, biological molecules, parts of cells and the like), which themselves manifest topographies having. structuring effects in the nanometer range, can be anchored essentially more stably on the contact surface so that, among other things, a good long-term stability exists, and the sensor can be maintained operative for a longer period of time with living cells or the like. It is at the same time especially advantageous if the shape of the biocomponents is preferably incorporated by means of a replica technique, and if the contact surface coating is provided with a complementary reverse structuring corresponding approximately to the shape of the biocomponents especially by means of a plasma bombarding technique or etching technique.
A direct adaptation of the surface structure or profiling to the topography of the biological systems or the biocomponents to be deposited consequently takes place, by means of which an especially good anchoring is assured. The transfer of the topography of the biocomponents to the active contact surface can take place with a known replica technique.
A modified form of the process provides that material particles for cluster formation, preferably comprising about 12,000 atoms with a kinetic energy smaller than about 1 eV/atom, are bombarded or sputtered onto the active contact surface for the formation of a contact surface coating with a loose structure or gaps.
An anchoring layer can thereby be built up on the contact surface of the sensor so that it which has a comparatively loose, porous structure. Gaps or holes are thereby formed in which, for example, immune receptors can be anchored. These biocomponents are very well anchored by interlocking, and the sensors thereby manifest a much better long term stability. At the same time, one also obtains an essentially greater measurement sensitivity, as the distance between the biocomponents and sensor contact surface is at least diminished, and the charge transfer process, which influences the sensor, consequently transpires closer to the sensor.
The measuring device produced according to the process of the invention is characterized in that the active contact surface of the sensors has a surface topography approximately adapted to the shape of the biocomponent to be examined. In this connection, it is particularly appropriate if the surface topography of the sensor contact surface is basically a complementary reverse structuring of the biocomponent in question. The advantages already presented in connection with the sensor production process are manifest thereby.
It is advantageous if the sensor has a field effect transistor with a contact surface coating, preferably of aluminum oxide, silicon nitride or similar structuring material. In comparison a the contact surface of silicon oxide, which is very smooth, aluminum oxide or silicon nitride has the advantage that roughened surfaces fitting the structure of the biocomponents can also be created with them. Aluminum oxide has a high pH sensitivity and a high sensitivity toward physiological signals, and improves the electrical coupling of a cell or similar biocomponent to the field effect transistor and consequently increases its output signal. Silicon nitride has a high voltage sensitivity.
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Cremer Christoph
Haberland Hellmut
Sieben Ulrich
Wolf Bernhard
Akin Gump Strauss Hauer & Feld L.L.P.
Chin Christopher L.
Micronas Intermetall GmbH
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