FUNCTIONAL LAYERS OF BIOMOLECULES AND LIVING CELLS, AND A NOVEL SYSTEM TO PRODUCE SUCH
First Claim
1. A coating process comprising the steps of:
- a) immersion of a conductive substrate in an aqueous dispersion with a conductivity lower than 100 μ
S/cm, said aqueous dispersion containing at least one biological agent, andb) application of an unbalanced (asymmetrical) AC signal between a counter electrode and said conductive substrate at defined frequency and amplitude between said counter electrode and said conductive substrate to induce said at least one biological agent to migrate electrophoretically, accumulate and form a bioactive deposit or bioactive coating on said conductive substrate over a period of time, wherein said bioactive deposit or bioactive coating is a biologically active film with a stacking of more than one monolayer.
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Accused Products
Abstract
The present invention concerns a new process for depositing a thick compact layer of biomolecules for instance such a layer with thickness in the μm scale and, for depositing a thick compact layer of cells in the μm scale. The deposited layer is made by application of an unbalanced (asymmetrical) alternating voltage polarization between two electrodes to a dissolved biomolecule or cell from low conductivity solutions. The process allows the rapid manufacturing of sensors and the coating of devices with functional cells and biomolecules. Examples are provided on the preparation of functional sensors such as a glucose, a lactose sensor, a hydrogen peroxide sensor and a glutamate sensor. Examples are also provided on the deposition of eukaryoric cells such as saccharomyces cerevisiae. The examples demonstrate a process that can be applied to coat devices with biomolecules and biological cells.
40 Citations
74 Claims
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1. A coating process comprising the steps of:
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a) immersion of a conductive substrate in an aqueous dispersion with a conductivity lower than 100 μ
S/cm, said aqueous dispersion containing at least one biological agent, andb) application of an unbalanced (asymmetrical) AC signal between a counter electrode and said conductive substrate at defined frequency and amplitude between said counter electrode and said conductive substrate to induce said at least one biological agent to migrate electrophoretically, accumulate and form a bioactive deposit or bioactive coating on said conductive substrate over a period of time, wherein said bioactive deposit or bioactive coating is a biologically active film with a stacking of more than one monolayer. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 18, 19, 20, 23, 25, 26, 27, 28)
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11. (canceled)
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13. (canceled)
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15. (canceled)
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21-22. -22. (canceled)
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24. (canceled)
- 29. An EPD system for electrocoating a conductive substrate, said system comprising a power supply connected to a signal generator to generate an unbalanced (asymmetrical) alternating current (AC) signal with a frequency in the range of 15 to 80 Hz and an amplitude of 80 to 300 Vp-p and preferably with a frequency in the range of 30 to 50 Hz and an amplitude of 160 to 200 Vp-p and, furthermore comprises a control system connected to signal generator for determining the parameters of the unbalanced (asymmetrical) AC, wherein said system is for electrocoating a conductive substrate with at least one bioactive layer, or bioactive coating comprising at least one type of a biological agent at a controllable average thickness above 100 nm, from a suspension in a aqueous working medium of one or more type of biological agents.
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33. (canceled)
- 35. An EPD system for electrocoating a conductive substrate, said system comprising a amplifier connected to a function generator to generate an unbalanced (asymmetrical) alternating current (AC) signal with a frequency in the range of 15 to 80 Hz and an amplitude of 80 to 300 Vp-p and, preferably with a frequency in the range of 30 to 50 Hz and an amplitude of 160 to 200 Vp-p and furthermore comprises a control system connected to signal generator for determining the parameters of the unbalanced (asymmetrical) AC, wherein said system is for electrocoating a conductive substrate with a stacking of more than one bioactive monolayer comprising at least one type of a biological agent at a controllable thickness from a suspension in a aqueous working medium comprising one or more type of biological agents.
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40. (canceled)
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42. A method of forming smooth deposits of at least one biological agent on a conductive substrate, for instance an implant, said smooth deposits having no visible defects and having a surface with a Ra of 10 to 50 μ
- m, preferably a Ra of 10 to 10000 nm, more preferably a Ra of 10 to 500 nm, and most preferably a Ra of 10-200 nm, said method using a coating process comprising the steps of;
a) immersion of a conductive substrate in an aqueous dispersion with a conductivity lower than 100 μ
S/cm, said aqueous dispersion containing at least one biological agent, and b) application of an unbalanced (asymmetrical) AC signal between a counter electrode and said conductive substrate at defined frequency and amplitude between said counter electrode and said conductive substrate to induce said at least one biological agent to migrate electrophoretically, accumulate and form a bioactive deposit or bioactive coating on said conductive substrate over a period of time, wherein said bioactive deposit or bioactive coating is a biologically active film with a stacking of more than one monolayer;
or using an EPD system for electrocoating a conductive substrate, said system comprising a amplifier connected to a function generator to generate an unbalanced (asymmetrical) alternating current (AC) signal with a frequency in the range of 15 to 80 Hz and an amplitude of 80 to 300 Vp-p and, preferably with a frequency in the range of 30 to 50 Hz and an amplitude of 160 to 200 Vp-p and furthermore comprises a control system connected to signal generator for determining the parameters of the unbalanced (asymmetrical) AC, wherein said system is for electrocoating a conductive substrate with a stacking of more than one bioactive monolayer comprising at least one type of a biological agent at a controllable thickness from a suspension in a aqueous working medium comprising one or more type of biological agents. - View Dependent Claims (43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56)
- m, preferably a Ra of 10 to 10000 nm, more preferably a Ra of 10 to 500 nm, and most preferably a Ra of 10-200 nm, said method using a coating process comprising the steps of;
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57. A method of manufacturing a biobattery, said method using a coating process comprising the steps of:
- a) immersion of electrodes in an aqueous dispersion with a conductivity lower than 100 μ
S/cm, said aqueous dispersion containing at least one biological agent, and b) application of an unbalanced (asymmetrical) AC signal between a counter electrode and said conductive substrate at defined frequency and amplitude between said counter electrode and said conductive substrate to induce said at least one biological agent to migrate electrophoretically, accumulate and form a bioactive deposit or bioactive coating on said electrodes over a period of time thereby providing electrodes of said biobattery, wherein said bioactive deposit or bioactive coating is a biologically active film with a stacking of more than one monolayer;
or using an EPD system for electrocoating electrodes, said system comprising a amplifier connected to a function generator to generate an unbalanced (asymmetrical) alternating current (AC) signal with a frequency in the range of 15 to 80 Hz and an amplitude of 80 to 300 Vp-p and, preferably with a frequency in the range of 30 to 50 Hz and an amplitude of 160 to 200 Vp-p and furthermore comprises a control system connected to signal generator for determining the parameters of the unbalanced (asymmetrical) AC, wherein said system is for electrocoating electrodes with a stacking of more than one bioactive monolayer comprising at least one type of a biological agent at a controllable thickness from a suspension in a aqueous working medium comprising one or more type of biological agents, thereby providing electrodes of said biobattery.
- a) immersion of electrodes in an aqueous dispersion with a conductivity lower than 100 μ
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58. A method of manufacturing a sensor, said method using a coating process comprising the steps of:
- a) immersion of a conductive substrate in an aqueous dispersion with a conductivity lower than 100 μ
S/cm, said aqueous dispersion containing at least one biological agent, and b) application of an unbalanced (asymmetrical) AC signal between a counter electrode and said conductive substrate at defined frequency and amplitude between said counter electrode and said conductive substrate to induce said at least one biological agent to migrate electrophoretically, accumulate and form a bioactive deposit or bioactive coating on said conductive substrate over a period of time thereby providing a coated sensor electrode, wherein said bioactive deposit or bioactive coating is a biologically active film with a stacking of more than one monolayer, said at least one biological agent is at least one enzyme and said coated sensor electrode is used for detecting an analyte;
or using an EPD system for electrocoating a conductive substrate, said system comprising a amplifier connected to a function generator to generate an unbalanced (asymmetrical) alternating current (AC) signal with a frequency in the range of 15 to 80 Hz and an amplitude of 80 to 300 Vp-p and, preferably with a frequency in the range of 30 to 50 Hz and an amplitude of 160 to 200 Vp-p and furthermore comprises a control system connected to signal generator for determining the parameters of the unbalanced (asymmetrical) AC, wherein said system is for electrocoating a conductive substrate with a stacking of more than one bioactive monolayer comprising at least one type of a biological agent at a controllable thickness from a suspension in a aqueous working medium comprising one or more type of biological agents thereby providing a coated sensor electrode, wherein said at least one biological agent is at least one enzyme and said coated sensor electrode is used for detecting an analyte. - View Dependent Claims (59, 60, 61, 62)
- a) immersion of a conductive substrate in an aqueous dispersion with a conductivity lower than 100 μ
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63. (canceled)
- 64. A sensor comprising an electrode with a electrophoretically deposited enzyme layer on said surface thereof and a layer of polyurethane coating in this order, wherein said electrophoretic deposition is realised with an unbalanced (asymmetrical) AC signal between a counter electrode and said electrode at defined frequency and amplitude between said counter electrode and said conductive substrate.
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74-76. -76. (canceled)
Specification