US6022316A
Expired / Lapsed
US
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Apparatus and method for electroporation of microporated tissue for enhancing flux rates for monitoring and delivery applications
Assignee: MIDCAP FUNDING III AS SUCCESSOR IN INTEREST TO MIDCAP FINANCIAL LLC LLC
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Filing: 1998-03-06
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Granted: 2000-02-08
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Expires: 2018-03-06
Abstract
Abstract An apparatus and a method for electroporating tissue. At least one micropore is formed to a predetermined depth through a surface of the tissue, and electrical voltage is applied between an electrode electrically coupled to the micropore and another electrode spaced therefrom. By applying electroporation to tissue that has been breached by a micropore, the electroporation effects can be targeted at tissue structures beneath the surface, such as capillaries, to greatly enhance the withdrawal of biological fluid, and the delivery for uptake of compounds into the tissue. In a preferred embodiment, a device is provided having elements that are suitable for microporating the tissue and which serve as the electroporation electrodes.
Inventors
- 👤 Jonathan A. Eppstein
- 👤 Michael R. Hatch
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:16
CPC Classifications
A; A61; A61N; A61N1/00; A61N1/02; A61N1/04; A61N1/0404; A61N1/0408; A61N1/0412; A61N1/0416; A61N1/18; A61N1/20; A61N1/30; A61N1/32; A61N1/325; A61N1/327; A61N1/0472; A61N1/0476
Claims Analysis
Total Claims: 51
Claim 1
Independent Claim
79 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue; positioning at least a first electrode on the surface of the tissue electrically coupled to the at least one micropore and a second electrode on the surface of the tissue spaced apart from the first electrode; and applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 2
Independent Claim
79 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue; positioning at least a first electrode on the surface of the tissue electrically coupled to the at least one micropore and a second electrode on the surface of the tissue spaced apart from the first electrode; and applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 3
Dependent Claim
64 words
The method of claim 1, wherein the step of applying electrical voltage comprises applying an electrical voltage of a sufficient magnitude between the first and second electrodes suitable to produce a potential drop exceeding a nominal threshold to achieve electroporation across the epithelial cell layer but not sufficient to electroporate membranes present in other tissue structures thereby achieving a selective electroporation of targeted membranes.
Claim 4
Dependent Claim
50 words
The method of claim 1, wherein the step of forming comprises forming first and second micropores spaced apart from each other, and wherein the first electrode is positioned to be electrically coupled to the first micropore, and the second electrode is positioned to be electrically coupled to the second micropore.
Claim 5
Dependent Claim
46 words
The method of claim 1, wherein the step of applying electrical voltage comprises applying a voltage pulse of a first polarity with respect to the first and second electrodes, followed by a voltage pulse of an opposite polarity with respect to the first and second electrodes.
Claim 6
Dependent Claim
76 words
The method of claim 1, wherein the step of forming comprises forming a plurality of micropores spaced apart from each other in the tissue, and the step of positioning comprises placing a plurality of electrodes each being electrically coupled to a different one of the micropores, and wherein the step of applying electrical voltage comprises applying electrical voltage pulses between different sets of the plurality of electrodes so as to electroporate the tissue in multiple directions.
Claim 7
Dependent Claim
40 words
The method of claim 5, wherein the step of applying comprises applying a voltage pulse of a first polarity between a first set of electrodes followed by a voltage pulse of an opposite polarity between the first set of electrodes.
Claim 8
Dependent Claim
30 words
A method of collecting biological fluid from the tissue comprising the steps of claim 1, and further comprising collecting biological fluid from the tissue through the at least one micropores.
Claim 9
Dependent Claim
15 words
The method of claim 7, and further comprising analyzing the biological fluid with a biosensor.
Claim 10
Dependent Claim
21 words
The method of claim 8, wherein the step of analyzing comprises determining a concentration of an analyte in the biological fluid.
Claim 11
Dependent Claim
66 words
The method of claim 1, wherein the step of forming the at least one micropore comprises applying a photosensitizing material to the surface of the tissue and irradiating the photosensitizing material with optical energy, whereby the photosensitizing material is responsive to the optical energy so as to heat up and conductively transfer heat to the surface of the tissue to form the at least one micropore.
Claim 12
Dependent Claim
57 words
The method of claim 1, and further comprising the step of deforming the surface of the tissue between the first and second electrodes so that the surface of the tissue sufficiently bulges between the first and second electrodes to place tissue structures desired to be electroporated in a principal current path between the first and second electrodes.
Claim 13
Dependent Claim
18 words
The method of claim 11, wherein the step of deforming comprises mechanically deforming the surface of the tissue.
Claim 14
Dependent Claim
19 words
The method of claim 11, wherein the step of deforming comprises applying suction to the surface of the tissue.
Claim 15
Dependent Claim
25 words
The method of claim 1, and further comprising the step of delivering a substance to the tissue at the at least two micropores formed therein.
Claim 16
Dependent Claim
92 words
The method of claim 1, wherein the step of forming the at least one micropore comprises applying a photosensitizing material to the surface of the tissue and irradiating the photosensitizing material with optical energy, whereby the photosensitizing material is responsive to the optical energy so as to heat up and conductively transfer heat to the surface of the tissue to form the at least one micropore, whereby the step of positioning the first and second electrodes comprises positioning conductive traces on a tissue-contacting side of the photosensitizing material registered with the micropores.
Claim 17
Dependent Claim
23 words
The method of claim 1, and further comprising the step of delivering a permeant into the tissue through the at least one micropore.
Claim 18
Dependent Claim
32 words
The method of claim 16, and further comprising the step of delivering a permeant into the tissue so as to cause the permeant to pass through the tissue structures that are electroporated.
Claim 19
Independent Claim
106 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue by placing an electrically heated probe at the surface of the tissue and supplying electrical current to the electrically heated probe so as to ablate the surface of the tissue in order to form the at least one micropore; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; and applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 20
Independent Claim
106 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue by placing an electrically heated probe at the surface of the tissue and supplying electrical current to the electrically heated probe so as to ablate the surface of the tissue in order to form the at least one micropore; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; and applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 21
Dependent Claim
32 words
The method of claim 18, wherein the electrically heated probe also serves as the first electrode such that the electrical voltage is applied between the electrically heated probe and the second electrode.
Claim 22
Independent Claim
119 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue by placing first and second electrically heated probes at the surface of the tissue spaced apart from each other and supplying electrical current to each of the first and second electrically heated probes so as to ablate the surface of the tissue in order to form two micropores spaced apart from each other; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 23
Independent Claim
119 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue by placing first and second electrically heated probes at the surface of the tissue spaced apart from each other and supplying electrical current to each of the first and second electrically heated probes so as to ablate the surface of the tissue in order to form two micropores spaced apart from each other; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 24
Dependent Claim
36 words
The method of claim 20, wherein the first and second electrically heated probes further serve as the first and second electrodes such that the electrical voltage is applied between the first and second electrically heated probes.
Claim 25
Independent Claim
90 words
An apparatus for microporation and electroporation of tissue, comprising: (a) a heated probe suitable for conducting heat to a surface of the tissue to form at least one micropore therein; (b) at least first and second electrodes suitable for being spaced apart from each other on the tissue; and (c) control means for supplying energy to the heated probe so as to cause formation of the at least one micropore in the tissue, and for applying an electrical voltage between the first and second electrodes suitable for electroporating the tissue.
Claim 26
Independent Claim
90 words
An apparatus for microporation and electroporation of tissue, comprising: (a) a heated probe suitable for conducting heat to a surface of the tissue to form at least one micropore therein; (b) at least first and second electrodes suitable for being spaced apart from each other on the tissue; and (c) control means for supplying energy to the heated probe so as to cause formation of the at least one micropore in the tissue, and for applying an electrical voltage between the first and second electrodes suitable for electroporating the tissue.
Claim 27
Dependent Claim
59 words
The apparatus of claim 22, wherein the control means supplies a magnitude of electrical voltage applied between the first and second electrodes suitable to produce a potential drop exceeding a nominal threshold to achieve electroporation across the epithelial cell layer but not sufficient to electroporate membranes present in other tissue structures thereby achieving a selective electroporation of targeted membranes.
Claim 28
Dependent Claim
51 words
The apparatus of claim 22, wherein the heated probe forms first and second micropores spaced apart from each other in the tissue, and wherein the first electrode is suitable for being electrically coupled to the first micropore and the second electrode is suitable for being electrically coupled to the second micropore.
Claim 29
Dependent Claim
34 words
The apparatus of claim 22, wherein the heated probe is an electrically heated probe, and wherein the control means supplies electrical current to the electrically heated probe to form the at least one micropore.
Claim 30
Dependent Claim
32 words
The apparatus of claim 25, wherein the electrically heated probe also serves as the first electrode such that the electrical voltage is applied between the electrically heated probe and the second electrode.
Claim 31
Dependent Claim
43 words
The apparatus of claim 22, wherein the heated probe comprises first and second electrically heated probes spaced apart from each other each responsive to electrical current supplied by the control means to form two micropores in the tissue spaced apart from each other.
Claim 32
Dependent Claim
42 words
The apparatus of claim 27, wherein the first and second electrically heated probes further serve as the first and second electrodes, the control means being coupled to the first and second electrically heated probes so as to apply the electrical voltage therebetween.
Claim 33
Dependent Claim
54 words
The apparatus of claim 28, and further comprising a tissue-contacting layer supporting the first and second electrically heated probes, and further comprising conductor means for coupling electrical current from the control means to the first and second electrically heated probes, and for applying the electrical voltage between the first and second electrically heated probes.
Claim 34
Dependent Claim
43 words
The apparatus of claim 22, wherein the control means applies a first voltage pulse of a first polarity with respect to the first and second electrodes, followed by a voltage pulse of an opposite polarity with respect to the first and second electrodes.
Claim 35
Dependent Claim
62 words
The apparatus of claim 22, and comprising a plurality of electrically heated probes each responsive to electrical current and suitable for forming a plurality of micropores spaced apart from each other in the tissue, and wherein the control means applies electrical voltage pulses between different sets of the plurality of electrically heated probes so as to electroporate the tissue in multiple directions.
Claim 36
Dependent Claim
38 words
The apparatus of claim 31, wherein the control means applies a voltage pulse of a first polarity between a first set of electrodes followed by a voltage pulse of an opposite polarity between the first set of electrodes.
Claim 37
Dependent Claim
70 words
The apparatus of claim 22, and comprising an integrated device for harvesting and analyzing biological fluid, the integrated device comprising a tissue-contact layer and a detecting layer, wherein the heated probe and the first and second electrodes are supported by the tissue-contacting layer, the detecting layer being positioned adjacent the tissue-contacting layer for detecting a characteristic of a biological fluid collected from the tissue through the at least one micropore.
Claim 38
Dependent Claim
13 words
The apparatus of claim 33, wherein the detecting layer comprises an electrochemical biosensor.
Claim 39
Dependent Claim
13 words
The apparatus of claim 33, wherein the detecting layer comprises a photometric sensor.
Claim 40
Dependent Claim
47 words
The apparatus of claim 22, and further comprising a mechanical element suitable for causing the surface of the tissue to sufficiently bulge between the first and second electrodes to place tissue structures desired to be electroporated in a principal current path between the first and second electrodes.
Claim 41
Dependent Claim
30 words
The apparatus of claim 22, and further comprising means for applying suction to the tissue so as to suck the surface of the tissue between the first and second electrodes.
Claim 42
Independent Claim
90 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; and applying a voltage pulse of a first polarity with respect to the first and second electrodes, followed by a voltage pulse of an opposite polarity with respect to the first and second electrodes to produce a desired electroporation in the tissue.
Claim 43
Independent Claim
90 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; and applying a voltage pulse of a first polarity with respect to the first and second electrodes, followed by a voltage pulse of an opposite polarity with respect to the first and second electrodes to produce a desired electroporation in the tissue.
Claim 44
Independent Claim
82 words
A method of collecting biological fluid from tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue; and collecting biological fluid from the tissue through the at least one micropores.
Claim 45
Independent Claim
82 words
A method of collecting biological fluid from tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue; and collecting biological fluid from the tissue through the at least one micropores.
Claim 46
Dependent Claim
15 words
The method of claim 39, and further comprising the step of analyzing the biological fluid.
Claim 47
Dependent Claim
21 words
The method of claim 40, wherein the step of analyzing comprises determining a concentration of an analyte in the biological fluid.
Claim 48
Independent Claim
128 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue, wherein the step of forming the at least one micropore comprises applying a photosensitizing material to the surface of the tissue and irradiating the photosensitizing material with optical energy, whereby the photosensitizing material is responsive to the optical energy so as to heat up and conductively transfer heat to the surface of the tissue to form the at least one micropore; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; and applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 49
Independent Claim
128 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue, wherein the step of forming the at least one micropore comprises applying a photosensitizing material to the surface of the tissue and irradiating the photosensitizing material with optical energy, whereby the photosensitizing material is responsive to the optical energy so as to heat up and conductively transfer heat to the surface of the tissue to form the at least one micropore; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; and applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 50
Independent Claim
99 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; applying suction to the surface of the tissue to deform the surface of the tissue between the first and second electrodes so that the tissue bulges between the first and second electrodes; and applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
Claim 51
Independent Claim
99 words
A method for electroporating tissue, comprising the steps of: forming at least one micropore to a predetermined depth through a surface of the tissue; positioning at least a first electrode electrically coupled to the at least one micropore and a second electrode spaced apart from the first electrode; applying suction to the surface of the tissue to deform the surface of the tissue between the first and second electrodes so that the tissue bulges between the first and second electrodes; and applying an electrical voltage between the first and second electrodes to produce a desired electroporation in the tissue.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 2003-02-07 | 2003-08-09 | 2004-02-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2007-02-07 | 2007-08-09 | 2008-02-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2011-02-07 | 2011-08-09 | 2012-02-08 | $7700.00 | Window Closed / Lapsed |