Variable-distance finger probe for electrical stimulation of target cells

Abstract

Disclosed herein is a variable-distance finger probe for electrical stimulation of a target region of a living body. The variable-distance finger probe includes two pieces coupled together with an adjustable middle distance, a distance-adjusting set located between the two pieces, and two electrodes attached onto front sides of the two pieces in front of each other with the adjustable middle distance. Each of the two pieces includes a finger holder at a back side of the piece encompassing at least one different finger of one hand of an expert. The distance-adjusting set includes at least two springs located between the front sides of the two pieces with an adjustable length adjusted by movements of the encompassed fingers, at least two shafts passing through the at least two springs, and at least one guide shaft located between the at least two shafts keeping the two pieces parallel with each other.

Description

VARIABLE-DISTANCE FINGER PROBE FOR ELECTRICAL STIMULATION OFTARGET CELLSTECHNICAL FIELD

[0001] The present disclosure generally relates to methods and apparatus for target cells’ treatment, ablation and / or delivery of therapeutic agents thereto via an electrical stimulation process, and particularly, to a probe mountable on an expert’s fingers having electrodes with an adjustable middle distance based on a location and size of a target region to be electrically stimulated.BACKGROUND ART

[0002] Needle-based electrodes are mostly used for electrical treatments in living tissues, for example, in electroporation treatments and electrochemical therapy (EChT). Many improvements and efforts have been made to fabricate and utilize electrical stimulation devices having needle electrodes. For example, A. Westersten et al. disclosed in a US patent application numbered as US 2006 / 0264807 Al a modular electrode system including a non-symmetrically arranged plurality of needle electrodes, in which a constant-current electrical pulse is applied to the plurality of needle electrodes. The modular electrode system may facilitate delivery of electrical energy to tissues in a manner that assures that the energy dose delivered lies consistently between an upper limit a lower limit; thereby, providing increased electroporation efficiencies.

[0003] However, conventional electrodes that are mostly utilized in EChT, electroporation, and electrochemotherapy have many drawbacks and design weaknesses. For example, conventional needle electrodes cannot be used in sensitive tissues, such as vessels, nerves, intestines, etc. due to bleeding in tissues and / or perforation of vital organs. On the other hand, some electrodes do not have an effective shape or structure in applying electrical stimulation due to a lack of a proper interaction surface between tissue and electrode. Moreover, in many cases, a physician is dealing with spaces where it is not possible to apply electrical stimulation due to a lack of a proper access, such as esophagus, surface of tracheal, behind bladder, anus entrance, narrow spaces inside at least one of digestive, respiratory, urogenital organs, or vessels, and combinations thereof.

[0004] Hence, there is a need in the art to overcome the problems and drawbacks of electrodes utilizing in an electrical stimulation treatment. There is a need in the art for electrically stimulation devices having less-invasive, and preferably, non-invasive electrodes. Specifically, there is a need for a device with electrodes to apply electrically stimulation to cells, which have a structure that minimizes a possibility of damage and bleeding to sensitive tissues (including vascular tissues, nervous tissues, etc.). Also, there is a need for electrodes that allow access to areas that cannot be reached with conventional electrodes.SUMMARY OF THE DISCLOSURE

[0005] This summary is intended to provide an overview of the subject matter of this patent, and is not intended to identify essential elements or key elements of the subject matter, nor is intended to be used to determine the scope of the claimed implementations. The proper scope of this patent may be ascertained from the claims set forth below in view of the detailed description below and the drawings.

[0006] In one general aspect, the present disclosure is directed to a variable-distance finger probe for electrical stimulation of a target region of a living body. In an exemplary embodiment, the variable -distance finger probe may include two pieces coupled together with an adjustable middle distance, a distance-adjusting set located between the two pieces, and two electrodes attached onto respective front sides of the two pieces in front of each other.

[0007] In an exemplary embodiment, each of the two pieces may include at least one finger holder at a back side of the piece. In an exemplary embodiment, each finger holder may encompass at least one different finger of one hand of an expert. In an exemplary embodiment, front sides of the two pieces may be located in front of each other with the adjustable middle distance.

[0008] In an exemplary embodiment, the distance-adjusting set may include at least two springs located between the front sides of the two pieces, at least two shafts, at least one guide shaft located between the at least two shafts, and a base part attached to a front side of a first piece of the two pieces. In an exemplary embodiment, a length of each spring of the at least two springs may be adjustable by movements of the encompassed fingers of the expert. In an exemplary embodiment, each shaft of the at least two shafts may pass through one spring of the at least two springs. In an exemplary embodiment, the at least one guide shaft may keep the two pieces parallel with each other. In an exemplary embodiment, the base part may includethree holes receiving the at least two shafts and the at least one guide shaft passing there through. In an exemplary embodiment, each piece of the two pieces may include three holes aligned with the three holes of the base part. In an exemplary embodiment, the three holes of each piece of the two pieces may receive the at least two shafts and the at least one guide shaft passing there through. In an exemplary embodiment, two ends of each shaft of the at least two shafts may be fastened onto back sides of the two pieces.

[0009] In an exemplary embodiment, each electrode of the two electrodes may be connected to a different pole of two poles of an electrical signal generator. In an exemplary embodiment, each electrode of the two electrodes may include a biocompatible electrically conductive flat plate with a surface area in a range of 0.25 cm2to 10 cm2. In an exemplary embodiment, each electrode of the two electrodes may include a biocompatible electrically conductive flat plate with a thickness in a range of 1 mm to 5 mm. In an exemplary embodiment, a distance between the two electrodes may include an adjustable distance in a range of 0.5 cm to 2 cm by pressing or releasing the at least two springs via movements of the encompassed fingers of the expert.

[0010] In an exemplary embodiment, each piece of the two pieces may include a piece of a biocompatible material. In an exemplary embodiment, each piece of the two pieces may include a piece of a biocompatible electrical insulator. In an exemplary embodiment, each piece of the two pieces may include a piece of a rigid biocompatible polymer. In an exemplary embodiment, each piece of the two pieces may include a piece of at least one of Teflon, polyethylene, polylactic acid, and combinations thereof.

[0011] In an exemplary embodiment, each electrode of the two electrodes may be covered with a thin layer of an electrical insulator. In an exemplary embodiment, each electrode of the two electrodes may be covered with a layer of the electrical insulator with a thickness in a range of 100 nm to 1 pm. In an exemplary embodiment, each electrode of the two electrodes may be covered with a layer of a biocompatible polymer. In an exemplary embodiment, each electrode of the two electrodes may be covered with a layer of a flexible biocompatible polymer. In an exemplary embodiment, each electrode of the two electrodes may be covered with a layer of at least one of silicone rubber, polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), and combinations thereof.

[0012] In an exemplary embodiment, the at least one finger holder of the first piece may include a first half-ring-shaped part protruded from the respective back side of the first piece. In an exemplary embodiment, the first half-ring-shaped part may be configured to encompassthumb of the one hand of the expert. In an exemplary embodiment, the at least one finger holder of the second piece may include a second half-ring-shaped part protruded from the respective back side of the second piece and a third half-ring-shaped part protruded from the respective back side of the second piece next to the second half-ring-shaped part. In an exemplary embodiment, the second half-ring-shaped part may be configured to encompass index finger of the one hand of the expert. In an exemplary embodiment, the third half-ring-shaped part may be configured to encompass middle finger of the one hand of the expert.

[0013] In an exemplary embodiment, each spring of the at least two springs may include a biocompatible spring with a variable length in a range of 0.5 cm to 2 cm. In an exemplary embodiment, the variable-distance finger probe may further include two electrically conductive lines. In an exemplary embodiment, each electrically conductive line of the two electrically conductive lines may include a distal end and a proximal end. In an exemplary embodiment, the distal end may be connected to one electrode of the two electrodes and the proximal end may be connected to a pole of the two poles of the electrical signal generator.

[0014] In another general aspect, the present disclosure is directed to a system for electrical stimulation of a target region of a living body. In an exemplary embodiment, the system may include a variable-distance finger probe, an electrical signal generator electrically connected to the variable -distance finger probe, and a processing unit electrically connected to the electrical signal generator.

[0015] In an exemplary embodiment, the variable -distance finger probe may be configured to transfer an electric field to the target region. In an exemplary embodiment, the variable -distance finger probe may be attached or mounted onto fingers of one hand of an expert. In an exemplary embodiment, the variable -distance finger probe may be put in the vicinity of the target region via insertion of the expert’s finger into the living body.

[0016] In an exemplary embodiment, the variable-distance finger probe may include two pieces coupled together with an adjustable middle distance, a distance-adjusting set located between the two pieces, and two electrodes attached onto respective front sides of the two pieces in front of each other. In an exemplary embodiment, each electrode of the two electrodes may be connected to a different pole of two poles of the electrical signal generator.

[0017] In an exemplary embodiment, the processing unit may include a memory having processor-readable instructions stored therein and a processor. In an exemplary embodiment, the processor may access the memory and execute the processor-readable instructions. In anexemplary embodiment, the processor may be utilized to perform a method when the processor-readable instructions are executed by the processor. In an exemplary embodiment, the method may include electrically stimulating a plurality of target cells in the target region by generating the electric field between the two electrodes inside the target region via applying an electric voltage between the two electrodes utilizing the electrical signal generator.

[0018] In an exemplary embodiment, electrically stimulating the plurality of target cells may include electroporating the plurality of target cells by applying at least one sequence of electric voltage pulses between the two electrodes. In an exemplary embodiment, applying the at least one sequence of electric voltage pulses may include applying at least one sequence of eight square-wave electric voltage pulses with a magnitude in a range of 500 V / cm to 1500 V / cm and a duration of 100 ps between the two electrodes. In an exemplary embodiment, the electrical signal generator may include an electrical pulse generator.

[0019] In an exemplary embodiment, electrically stimulating the plurality of target cells may include electrolyzing peripheral medium surrounding the plurality of target cells within a set of pre-determined time steps. In an exemplary embodiment, the set of pre-determined time steps may include at least one of a set of equal time steps, a set of unequal time steps, and combinations thereof. In an exemplary embodiment, each time step of the set of pre-determined time steps may include a time period in a range between 1 minutes and 3 minutes. In an exemplary embodiment, the electrical signal generator comprises a DC voltage generator.

[0020] In an exemplary embodiment, each of the two pieces may include at least one finger holder at a back side of the piece. In an exemplary embodiment, each finger holder may encompass at least one different finger of one hand of an expert. In an exemplary embodiment, front sides of the two pieces may be located in front of each other with the adjustable middle distance.

[0021] In an exemplary embodiment, the distance-adjusting set may include at least two springs located between the front sides of the two pieces, at least two shafts, at least one guide shaft located between the at least two shafts, and a base part attached to a front side of a first piece of the two pieces. In an exemplary embodiment, a length of each spring of the at least two springs may be adjustable by movements of the encompassed fingers of the expert. In an exemplary embodiment, each shaft of the at least two shafts may pass through one spring of the at least two springs. In an exemplary embodiment, the at least one guide shaft may keep the two pieces parallel with each other. In an exemplary embodiment, the base part may includethree holes receiving the at least two shafts and the at least one guide shaft passing there through. In an exemplary embodiment, each piece of the two pieces may include three holes aligned with the three holes of the base part. In an exemplary embodiment, the three holes of each piece of the two pieces may receive the at least two shafts and the at least one guide shaft passing there through. In an exemplary embodiment, two ends of each shaft of the at least two shafts may be fastened onto back sides of the two pieces.

[0022] In an exemplary embodiment, each electrode of the two electrodes may include a biocompatible electrically conductive flat plate with a surface area in a range of 0.25 cm2to 10 cm2. In an exemplary embodiment, each electrode of the two electrodes may include a biocompatible electrically conductive flat plate with a thickness in a range of 1 mm to 5 mm. In an exemplary embodiment, a distance between the two electrodes may include an adjustable distance in a range of 0.5 cm to 2 cm by pressing or releasing the at least two springs via movements of the encompassed fingers of the expert.

[0023] In an exemplary embodiment, each piece of the two pieces may include a piece of a biocompatible material. In an exemplary embodiment, each piece of the two pieces may include a piece of a biocompatible electrical insulator. In an exemplary embodiment, each piece of the two pieces may include a piece of a rigid biocompatible polymer. In an exemplary embodiment, each piece of the two pieces may include a piece of at least one of Teflon, polyethylene, polylactic acid, and combinations thereof.

[0024] In an exemplary embodiment, each electrode of the two electrodes may be covered with a thin layer of an electrical insulator. In an exemplary embodiment, each electrode of the two electrodes may be covered with a layer of the electrical insulator with a thickness in a range of 100 nm to 1 pm. In an exemplary embodiment, each electrode of the two electrodes may be covered with a layer of a biocompatible polymer. In an exemplary embodiment, each electrode of the two electrodes may be covered with a layer of a flexible biocompatible polymer. In an exemplary embodiment, each electrode of the two electrodes may be covered with a layer of at least one of silicone rubber, polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), and combinations thereof.

[0025] In an exemplary embodiment, the at least one finger holder of the first piece may include a first half-ring-shaped part protruded from the respective back side of the first piece. In an exemplary embodiment, the first half-ring-shaped part may be configured to encompass thumb of the one hand of the expert. In an exemplary embodiment, the at least one finger holderof the second piece may include a second half-ring-shaped part protruded from the respective back side of the second piece and a third half-ring-shaped part protruded from the respective back side of the second piece next to the second half-ring-shaped part. In an exemplary embodiment, the second half-ring-shaped part may be configured to encompass index finger of the one hand of the expert. In an exemplary embodiment, the third half-ring-shaped part may be configured to encompass middle finger of the one hand of the expert.

[0026] In an exemplary embodiment, each spring of the at least two springs may include a biocompatible spring with a variable length in a range of 0.5 cm to 2 cm. In an exemplary embodiment, the variable-distance finger probe may further include two electrically conductive lines. In an exemplary embodiment, each electrically conductive line of the two electrically conductive lines may include a distal end and a proximal end. In an exemplary embodiment, the distal end may be connected to one electrode of the two electrodes and the proximal end may be connected to a pole of the two poles of the electrical signal generator.BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The drawing figures depict one or more implementations in accord with the present teachings, by way of example only, not by way of limitation. In the figures, like reference numerals refer to the same or similar elements.

[0028] FIG. 1A schematically shows a side view of an exemplary variable-distance finger probe, consistent with one or more exemplary embodiments of the present disclosure.

[0029] FIG. IB schematically shows an exploded view of an exemplary variable-distance finger probe, consistent with one or more exemplary embodiments of the present disclosure.

[0030] FIG. 1C schematically shows a top view of an exemplary variable-distance finger probe, consistent with one or more exemplary embodiments of the present disclosure.

[0031] FIG. ID schematically shows an exemplary first piece of an exemplary variabledistance finger probe, consistent with one or more exemplary embodiments of the present disclosure, respectively.

[0032] FIG. IE schematically shows an exemplary second piece of an exemplary variabledistance finger probe, consistent with one or more exemplary embodiments of the present disclosure, respectively.

[0033] FIG. 2 shows an exemplary system for electrical stimulation of an exemplary target region, consistent with one or more exemplary embodiments of the present disclosure.

[0034] FIG. 3 shows an exemplary method for electrical stimulation of an exemplary plurality of target cells, consistent with one or more exemplary embodiments of the present disclosure.

[0035] FIG. 4 shows an example computer system in which an embodiment of the present disclosure, or portions thereof, may be implemented as computer-readable code, consistent with one or more exemplary embodiments of the present disclosure.DESCRIPTION OF EMBODIMENTS

[0036] In the following detailed description, numerous specific details are set forth by way of examples in order to provide a thorough understanding of the relevant teachings. However, it should be apparent that the present teachings may be practiced without such details. In other instances, well known methods, procedures, components, and / or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

[0037] Herein, methods, systems, and devices are disclosed for an electrical treatment (e.g., electroporation or electrochemical therapy (EChT)) of a plurality of target cells, particularly cells of a patient's tissues. In an exemplary embodiment, methods and devices may be utilized for target cells’ ablation (e.g., tumor cells destruction) and / or delivery of a substance (e.g., a drug, a diagnostic agent, a therapeutic agent, etc.) to an exemplary plurality of target cells. In an exemplary embodiment, an exemplary plurality of target cells may include cancer cells. In an exemplary embodiment, an exemplary device may be disclosed for target cell’s electrical stimulation. In an exemplary embodiment, an exemplary device may include a probe for electrical stimulation of an exemplary plurality of target cells. In an exemplary embodiment, an exemplary device may include two non-invasive plate-shaped electrodes to be placed at two sides of an exemplary plurality of target cells. In an exemplary embodiment, an electric field may be generated between exemplary electrodes affecting an exemplary plurality of target cells. In an exemplary embodiment, an exemplary electric field may be generated by applying an electrical voltage between exemplary electrodes.

[0038] In an exemplary embodiment, an exemplary probe may be mounted on a subject’s fingers and a distance between two exemplary electrodes may be adjusted by pressing subject’s fingers towards together or retracting subject’s fingers from each other. In an exemplary embodiment, an exemplary distance between two exemplary electrodes may be adjusted based on a location and / or a size of a region an exemplary plurality of target cells located therein. Inan exemplary embodiment, an exemplary probe may be utilized for a non-invasive electrical treatment of an exemplary plurality of target cells located at a hard-to-access and / or a sensitive location in a living body of a human or an animal. In an exemplary embodiment, an exemplary probe may be utilized for non-invasive electrical treatment of an exemplary plurality of target cells located at areas of an exemplary living body not accessible except a physician's finger. In an exemplary embodiment, an exemplary probe may be utilized for an exemplary non-invasive electrical treatment of an exemplary plurality of target cells located at a location of at least one of inside esophagus, surface of tracheal, behind bladder, anus entrance, or narrow spaces inside at least one of digestive, respiratory, urogenital organs, or vessels, and combinations thereof.

[0039] In an exemplary embodiment, an exemplary probe may be utilized for at least one of electrically stimulating of an exemplary plurality of target cells, electroporating an exemplary plurality of target cells, generating an electric field among an exemplary plurality of target cells, electrochemical therapy (ECT) of an exemplary plurality of target cells, electrically ablation of an exemplary plurality of target cells, and combinations thereof. In an exemplary embodiment, an exemplary probe may be utilized for at least one of electrically stimulating of an exemplary plurality of target cells in an area of an exemplary living body, where inserting a needle electrode there into may not be allowed or inserting a needle there may be harmful. As used herein, “target cells” may refer to cells of a part of a living body to be treated by an electrical stimulation (e.g., electroporation or EChT); allowing for treatment of exemplary cells including ablating exemplary cells and / or delivery of specific substances (e.g., a drug, a diagnostic agent, a therapeutic agent, etc.) to exemplary cells.

[0040] In an exemplary embodiment, in many cases of sarcoma or carcinoma, a small, sensitive to invasive insertion of electrodes, and / or hard to access part of an exemplary living body may include cancer cells to be electroporated or treated by an EChT process. In some cases, inserting an electrode of common electroporation and / or EChT devices may not be possible due to a very narrow or small space of a target region containing an exemplary plurality of target cells. Furthermore, inserting of needle-like electrodes may cause damage or bleeding in an exemplary sensitive target region. In an exemplary embodiment, an exemplary target region may be located in sensitive tissues, such as vessels, nerves, intestines, etc. due to bleeding in such tissues and / or where invasive electrical stimulation methods and devices cannot be used. In an exemplary embodiment, an exemplary target region may include parts of body that may be hard to access. In an exemplary embodiment, an exemplary target region may be located inparts of an exemplary body, where accessing there into by a needle-shaped electrode may cause perforation of vital organs. In such cases, electrodes of an exemplary probe may be put in contact or in the vicinity of an exemplary target region with no invasive insertion or any limitations about accessibility to an exemplary target region.

[0041] FIG. 1A schematically shows a side view of a variable-distance finger probe 100, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, finger probe 100 may include two pieces 102 and 104 coupled together with an adjustable middle distance 118, a distance-adjusting set 101 located between two pieces 102 and 104, and two electrodes 114 and 116 attached to two pieces 102 and 104. In an exemplary embodiment, two pieces 102 and 104 may include a first piece 102 and a second piece 104.

[0042] FIG. IB schematically shows an exploded view of variable-distance finger probe 100, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, each piece 102 or 104 may include at least one finger holder 120 or 122 at a back side 102b or 104b of corresponding piece 102 or 104. In an exemplary embodiment, each finger holder 120 or 122 may encompass at least one different finger of a human’s hand (e.g., an expert, a physician, or a surgeon). In an exemplary embodiment, front sides 102a or 104a of two pieces 102 or 104 may be located in front of each other with adjustable middle distance 118 (illustrated in FIG. 1A). In an exemplary embodiment, each finger holder 120 or 122 may include a half-ring-shaped part (e.g., half-ring-shaped parts 120a, 122a, and 122b) protruded out from corresponding back side 102b or 104b of corresponding piece 102 or 104. In an exemplary embodiment, half-ring shape of finger holders 120 and 122 may allow for mounting variable-distance finger probe 100 on an exemplary human’s hand. In an exemplary embodiment, adjustable middle distance 118 between two pieces 102 and 104 may be adjusted by pressing or retracting fingers of an exemplary human’s hand against each other. For further clearance, FIG. 1C schematically shows a top view of variable-distance finger probe 100, consistent with one or more exemplary embodiments of the present disclosure.

[0043] In an exemplary embodiment, each piece 102 (or 104) may include a piece of a biocompatible material. In an exemplary embodiment, each piece 102 (or 104) may include a piece of a biocompatible electrical insulator. In an exemplary embodiment, each piece 102 (or 104) may include a piece of a biocompatible polymer. In an exemplary embodiment, each piece 102 (or 104) may include a piece of a biocompatible rigid polymer. In an exemplary embodiment, each piece 102 (or 104) may include a piece of at least one of Teflon,polyethylene, polylactic acid, and combinations thereof. In an exemplary embodiment, each finger holder 120 or 122 may include a piece of a flexible / rigid biocompatible material. In an exemplary embodiment, each finger holder 120 or 122 may include a piece of at least one of Teflon, polyethylene, polylactic acid, silicone rubber, polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), and combinations thereof. In an exemplary embodiment, parts of piece 102 (or 104)other than finger holders 120 and 122 may be made of another biocompatible material, such as stainless steel. In an exemplary embodiment, some parts or all surface of two pieces 102 and 104 may be covered with a layer of an exemplary biocompatible polymer. In an exemplary embodiment, a layer of an exemplary biocompatible polymer may be coated on electrical conductive (e.g., metallic parts) of variable -distance finger probe 100.

[0044] In an exemplary embodiment, each electrode of two electrodes two electrodes 114 and 116 may be covered with a thin layer of an electrical insulator. In an exemplary embodiment, each electrode of two electrodes two electrodes 114 and 116 may be covered with a layer of an exemplary electrical insulator with a thickness in a range of about 100 nm to about 1 pm. In an exemplary embodiment, each electrode of two electrodes two electrodes 114 and 116 may be covered with a layer of a biocompatible polymer. In an exemplary embodiment, each electrode of two electrodes two electrodes 114 and 116 may be covered with a layer of a flexible biocompatible polymer. In an exemplary embodiment, each electrode of two electrodes two electrodes 114 and 116 may be covered with a layer of at least one of silicone rubber, polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), and combinations thereof. In an exemplary embodiment, a presence of an exemplary layer of electrical insulator may prevent possible tissue bums in the vicinity of two electrodes 114 and 116 due to an increase of electrical current density around surface of two electrodes 114 and 116 while applying an electrical voltage between two electrodes 114 and 116.

[0045] FIGs. ID and IE schematically show two pieces 102 and 104, consistent with one or more exemplary embodiments of the present disclosure, respectively. In an exemplary embodiment, finger holder 120 of first piece 102 may include a first half-ring-shaped part 120a with a size and shape allowing for locating thumb of an exemplary human’s hand therein. In an exemplary embodiment, finger holder 122 of second piece 104 may include a second halfring-shaped part 122a with a size and shape allowing for locating index finger of an exemplary human’s hand therein. In an exemplary embodiment, an exemplary human’s hand may be placed inside or outside an exemplary living body so that a portion or whole of an exemplarytarget region may be placed between two electrodes 114 and 116. In an exemplary embodiment, adjustable middle distance 118 may be adjusted by pressing or retracting thumb and index finger of an exemplary human’s hand against each other. In an exemplary embodiment, for more accurate adjustment of adjustable middle distance 118 and more stable placement of variable-distance finger probe 100 in the vicinity of an exemplary target region, finger holder 122 of second piece 104 may further include a third half-ring-shaped part 122b with a size and shape allowing for locating middle finger of an exemplary human’s hand therein. In an exemplary embodiment, adjustable middle distance 118 may be adjusted by pressing or retracting thumb against index and middle fingers of an exemplary human’s hand.

[0046] Regarding FIGs. 1A and IB, distance-adjusting set 101 may include at least two springs 106a and 106b, at least two shafts 108a and 108b passed through corresponding at least two springs 106a and 106b, at least one guide shaft 110 located between at least two shafts 108a and 108b, and a base part 112 attached to a front side 102a of first piece 102. In an exemplary embodiment, distance-adjusting set 101 may couple first piece 102 to second piece 104 in a parallel relation with a freedom of movement against each other along adjustable middle distance 118. In an exemplary embodiment, two pieces 102 and 104 may move against each other by pressing or retracting an exemplary human’s fingers placed inside finger holders 120 and 122.

[0047] In an exemplary embodiment, at least two springs 106a and 106b may be located between corresponding front sides 102a and 104a of two pieces 102 and 104. In an exemplary embodiment, the length of each spring 106a (or 106b) may be adjustable by the movement of encompassed fingers of an exemplary human’s hand. In an exemplary embodiment, each spring 106a (or 106b) may include a biocompatible spring. In an exemplary embodiment, each spring 106a (or 106b) may include a stainless steel spring, for example, a spring made of 304 stainless steel or 316 stainless steel. In an exemplary embodiment, each spring 106a (or 106b) may have a variable length in a range of 0.5 cm to 2 cm so that adjustable middle distance 118 between two pieces 102 and 104 may be adjustable in a range of 0.5 cm to 2 cm by an exemplary human’s fingers movements.

[0048] In an exemplary embodiment, base part 112 may be attached to front side 102a of first piece 102. In an exemplary embodiment, base part 112 may include three holes 112a, 112b, and 112c. In an exemplary embodiment, holes 112a and 112b may receive at least two shafts 108a and 108b, and hole 112c may receive guide shaft 110 passing there through. In anexemplary embodiment, three holes 112a, 112b, and 112c may be continued along base part 112 and from front side 102a to back side 102b of first piece 102. In an exemplary embodiment, second piece 104 may include three holes 124a, 124b, and 124c aligned with three holes 112a, 112b, and 112c of base part 112 so that holes 124a and 124b may receive at least two shafts 108a and 108b, and hole 124c may receive guide shaft 110 passing there through; thereby, resulting in connecting two pieces 102 and 104 together with a free movement against each other.

[0049] In an exemplary embodiment, shaft 108a may pass through hole 112a, spring 106a, and hole 124a, and may be fastened at back side 104b of piece 104 exiting hole 124a. Likewise, in an exemplary embodiment, shaft 108b may pass through hole 112b, spring 106b, and hole 124b, and may be fastened at back side 104b of piece 104 exiting hole 124b. In an exemplary embodiment, shafts 108a and 108b may be fastened at back side 104b of piece 104 using fastening agents 126a and 126b, respectively. In an exemplary embodiment, each fastening agent 126a or 126b may include a stainless steel nut.

[0050] In an exemplary embodiment, at least one guide shaft 110 may be located between at least two shafts 108a and 108b. In an exemplary embodiment, at least one guide shaft 110 may keep two pieces 102 and 104 in a parallel relation with each other, particularly, when two pieces 102 and 104 are moved closer or further apart manipulated by an exemplary human’s fingers. In an exemplary embodiment, at least one guide shaft 110 may be freely placed between at least two shafts 108a and 108b and passed through holes 112c and 124c. In an exemplary embodiment, each shaft of at least two shafts 108a and 108b or at least one guide shaft 110 may include a shaft made of a biocompatible material. In an exemplary embodiment, each shaft of at least two shafts 108a and 108b or at least one guide shaft 110 may include a stainless steel shaft, for example, a shaft made of 304 stainless steel or 316 stainless steel.

[0051] Referring to FIGs. 1A and IB, two electrodes 114 and 116 may be attached onto corresponding front sides 102a and 104a of two pieces 102 and 104 in front of each other. In an exemplary embodiment, each electrode 114 (or 116) may be fastened onto front side 102a (or 104a) using a fastener 128 and a nut (not illustrated) at back side 102b (or 104b). In an exemplary embodiment, each electrode 114 (or 116) may include a biocompatible electrically conductive flat plate. In an exemplary embodiment, each electrode 114 (or 116) may be made of stainless steel, for example, 304 stainless steel or 316 stainless steel. In an exemplary embodiment, each electrode 114 (or 116) may have a surface area in a range of about 0.25 cm2to about 10 cm2. In an exemplary embodiment, each electrode 114 (or 116) may have a thickness in a range of about 1 mm to about 5 mm. In an exemplary embodiment, each electrode 114 (or 116) may include a plate with dimensions of about 2 cm * 3 cm. In an exemplary embodiment, a distance between two electrodes 114 and 116 may be equal to adjustable middle distance 118 in a range of 0.5 cm to 2 cm adjusted by an exemplary human’s fingers movements.

[0052] In an exemplary embodiment, variable-distance finger probe 100 may be used for electrical stimulation of a target region in a living body, for example, a human or an animal. In an exemplary embodiment, variable-distance finger probe 100 may be mounted on an exemplary human’s fingers (e.g., an expert, a physician, or a surgeon) at one hand and two electrodes 114 and 116 may be placed in the vicinity of an exemplary target region so that a plurality of target cells to be stimulated in an exemplary target region may be placed between two electrodes 114 and 116. In an exemplary embodiment, adjustable middle distance 118 between two electrodes 114 and 116 may be adjusted by pressing or retracting human’s fingers against each other. In an exemplary embodiment, two electrodes 114 and 116 may be electrically connected to an electrical signal generator 202 (illustrated in FIG. 2) and an electric field may be generated in an exemplary target region; thereby, resulting in stimulating an exemplary plurality of target cells. In an exemplary embodiment, variable-distance finger probe 100 may be placed inside or outside an exemplary living body depending on the location of an exemplary target region so that two electrodes 114 and 116 may be placed adjacent to an exemplary target region. In an exemplary embodiment, variable-distance finger probe 100 may be placed inside or outside an exemplary living body so that two electrodes 114 and 116 may grasp an exemplary target region there between. In an exemplary embodiment, two electrodes 114 and 116 may be placed inside an exemplary living body via a process, including at least one of during a surgery, through an incision cut in the vicinity of an exemplary target region, through a lumen of an exemplary living body, by inserting an exemplary human’s hand into an exemplary living body, and combinations thereof. In an exemplary embodiment, two electrodes 114 and 116 may be placed outside an exemplary living body in the vicinity of an exemplary target region, for example, on skin of an exemplary living body in the vicinity of an exemplary target region. In an exemplary embodiment, a location of variable -distance finger probe 100 and adjustable middle distance 118 may be adjusted by an exemplary human’s fingers so that an exemplary electric field may be generated in an exemplary target region by applying anelectrical signal (i.e., an electrical voltage) between two electrodes 114 and 116 utilizing electrical signal generator 202.

[0053] In an exemplary embodiment, variable-distance finger probe 100 may be utilized for applying a therapeutic or drug delivery method to an exemplary target region via electrical stimulation of an exemplary plurality of target cells of an exemplary target region. In an exemplary embodiment, variable-distance finger probe 100 may be utilized for electrical stimulation of tumor cells of a cancer patient. In an exemplary embodiment, a system for electrical stimulation of an exemplary target region including variable-distance finger probe 100 may be disclosed. FIG. 2 shows a system 200 for electrical stimulation of an exemplary target region, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, system 200 may include variable-distance finger probe 100, electrical signal generator 202, and a processing unit 204.

[0054] In an exemplary embodiment, variable-distance finger probe 100 may further include two electrically conductive lines 206 and 208. In an exemplary embodiment, each electrically conductive line 206 (or 208) may include a distal end 206a (or 208a) and a proximal end 206b (or 208b). In an exemplary embodiment, distal end 206a may be connected to electrode 114 and proximal end 206b may be connected to a pole 202a of electrical signal generator 202. In an exemplary embodiment, distal end 208a may be connected to electrode 116 and proximal end 208b may be connected to a pole 202b of electrical signal generator 202.

[0055] In an exemplary embodiment, electrical signal generator 202 may include an electrical voltage generator or a power supply to be utilized for applying an electric field between two electrodes 114 and 116 of variable-distance finger probe 100. In an exemplary embodiment, electrical signal generator 202 may include a DC voltage generator. In an exemplary embodiment, electrical stimulation of an exemplary plurality of target cells of an exemplary target region may include electrochemical therapy (EChT) of an exemplary plurality of target cells of an exemplary target region. In an exemplary embodiment, electrical signal generator 202 may be utilized to apply a DC voltage between two electrodes 114 and 116 while two electrodes 114 and 116 being put in contact or in the vicinity of an exemplary target region; thereby, resulting in electrolysis of an exemplary target region stimulating an exemplary plurality of target cells therein. In an exemplary embodiment, electrical signal generator 202 may include an electrical pulse generator. In an exemplary embodiment, electrical signal generator 202 may include an electroporation pulse generator. In an exemplary embodiment,electrical stimulation of an exemplary plurality of target cells of an exemplary target region may include electroporation of an exemplary plurality of target cells of an exemplary target region. In an exemplary embodiment, electrical signal generator 202 may be utilized to apply electrical pulses between two electrodes 114 and 116 while two electrodes 114 and 116 being put in contact or in the vicinity of an exemplary target region; thereby, resulting in generating a pulsed electric field within an exemplary target region stimulating an exemplary plurality of target cells therein.

[0056] Referring to FIG. 2, processing unit 204 may be electrically connected to electrical signal generator 202 via a wireless connection or utilizing respective electrically conductive wire 210. In an exemplary embodiment, processing unit 204 may include a memory having processor-readable instructions stored therein and a processor. In an exemplary embodiment, an exemplary processor may be utilized to access an exemplary memory and execute exemplary processor-readable instructions. In an exemplary embodiment, executing exemplary processor-readable instructions by an exemplary processor may configure an exemplary processor to perform a method. In an exemplary embodiment, an exemplary method may include applying a therapeutical treatment or a drug delivery process to an exemplary plurality of target cells inside an exemplary living body by electrically stimulating an exemplary plurality of target cells. In an exemplary embodiment, an exemplary method may include at least one of treating an exemplary plurality of target cells, ablating an exemplary plurality of target cells, delivering a drug or therapeutical substance to an exemplary plurality of target cells, and combinations thereof. In an exemplary embodiment, an exemplary method may include electroporation of an exemplary plurality of target cells.

[0057] FIG. 3 shows a method 300 for electrical stimulation of an exemplary plurality of target cells, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, method 300 may include putting variable-distance finger probe 100 in the vicinity of an exemplary target region of an exemplary living body containing an exemplary plurality of target cells (step 302), grasping a portion or whole of an exemplary target region between two electrodes 114 and 116 of variable-distance finger probe 100 by adjusting adjustable middle distance 118 (step 304), and electrically stimulating an exemplary plurality of target cells by generating an exemplary electric field between two electrodes 114 and 116 of variable-distance finger probe 100 inside an exemplary portion or whole of target region (step 306). In an exemplary embodiment, method 300 may be carried out utilizingvariable-distance finger probe 100 and system 200 described herein above. So, method 300 may be described herein below in connection with FIGs. 1A-1E and FIG. 2.

[0058] In further detail with respect to step 302, variable -distance finger probe 100 may be put in the vicinity of an exemplary target region of an exemplary living body, where an exemplary target region may contain an exemplary plurality of target cells. In an exemplary embodiment, step 302 may include putting variable-distance finger probe 100 in contact with an exemplary target region of an exemplary living body. In an exemplary embodiment, putting variabledistance finger probe 100 in contact with an exemplary target region of an exemplary living body may include mounting variable-distance finger probe 100 on an exemplary human’s fingers and placing variable -distance finger probe 100 inside or outside of an exemplary living body in the vicinity of an exemplary target region guided by movements of an exemplary human’s fingers. In an exemplary embodiment, putting variable-distance finger probe 100 in contact with an exemplary target region may include at least one of inserting variable-distance finger probe 100 into an exemplary living body in the vicinity of an exemplary target region, putting variable-distance finger probe 100 outside of an exemplary living body in contact with an exemplary target region, and combinations thereof.

[0059] In an exemplary embodiment, an exemplary target region may include an internal and / or an external region of an exemplary living body. In an exemplary embodiment, an exemplary target region may be located inside an exemplary living body or may be a superficial region of an exemplary living body. In an exemplary embodiment, an exemplary target region may include an internal region located in sensitive or hard to access tissues, such as vessels, nerves, intestines, etc. In an exemplary embodiment, putting variable-distance finger probe 100 in contact with an exemplary target region may include inserting variable-distance finger probe 100 into an exemplary living body via a process, including at least one of during a surgery, through an incision cut in the vicinity of an exemplary target region, through a lumen of an exemplary living body, by inserting an exemplary human’s hand into an exemplary living body, and combinations thereof.

[0060] In an exemplary embodiment, an exemplary target region may include an external region, such as surface nodules. In an exemplary embodiment, putting variable -distance finger probe 100 in contact with an exemplary target region may include placing outside an exemplary living body in the vicinity of an exemplary target region, for example, on skin of an exemplary living body in the vicinity of an exemplary target region.

[0061] In an exemplary embodiment, putting variable-distance finger probe 100 in contact with an exemplary target region of an exemplary living body may include placing tips of an exemplary human’s fingers at a location of at least one of inside esophagus, surface of tracheal, behind bladder, anus entrance, a narrow space inside at least one of digestive, respiratory, urogenital organs, or vessels, near surface modules, and combinations thereof. In an exemplary embodiment, putting variable-distance finger probe 100 in contact with an exemplary target region may include placing variable-distance finger probe 100 on an exemplary plurality of target cells to be treated, such as surface nodules. In an exemplary embodiment, putting variable-distance finger probe 100 in contact with an exemplary target region may include sweeping or scanning an exemplary target region by variable-distance finger probe 100 via moving an exemplary human’s finger inside / on an exemplary target region while conducting steps 304 and 306 of method 300.

[0062] In further detail with respect to step 304, step 304 may include grasping a portion or whole of an exemplary target region between two electrodes 114 and 116 of variable-distance finger probe 100 by adjusting adjustable middle distance 118. In an exemplary embodiment, step 304 may include pressing or retracting an exemplary human’s fingers placed in finger holders 120 and 122 towards or apart each other so that an exemplary portion or whole of an exemplary target region may be placed between two electrodes 114 and 116. In an exemplary embodiment, step 304 may include encompassing an exemplary portion or whole of an exemplary target region within two electrodes 114 and 116 with adjustable middle distance 118 in a range of about 0.5 cm to about 2 cm there within.

[0063] In further detail with respect to step 306, step 306 may include electrically stimulating an exemplary plurality of target cells by generating an exemplary electric field between two electrodes 114 and 116 of variable-distance finger probe 100 inside an exemplary portion or whole of target region grasped between two electrodes 114 and 116. In an exemplary embodiment, electrically stimulating an exemplary plurality of target cells (step 306) may include electrochemical therapy (EChT) of an exemplary plurality of target cells. In an exemplary embodiment, electrically stimulating an exemplary plurality of target cells may include electrolyzing peripheral medium surrounding an exemplary plurality of target cells within a set of pre-determined time steps. In an exemplary embodiment, an exemplary set of pre-determined time steps may include at least one of a set of equal time steps, a set of unequal time steps, and combinations thereof. In an exemplary embodiment, each time step of anexemplary set of pre -determined time steps may include a time period in a range of about 1 minutes to about 3 minutes. In an exemplary embodiment, electrical signal generator 202 may include a DC voltage generator. In an exemplary embodiment, a DC voltage may be applied between two electrodes 114 and 116; thereby, resulting in electrolyzing peripheral medium surrounding an exemplary plurality of target cells.

[0064] In an exemplary embodiment, electrically stimulating an exemplary plurality of target cells (step 306) may include inducing electroporation to an exemplary plurality of target cells by generating a pulsed electric field between two electrodes 114 and 116 inside an exemplary target region. In an exemplary embodiment, step 306 may include inducing electroporation to an exemplary plurality of target cells by generating an exemplary pulsed electric field between two electrodes 114 and 116 inside an exemplary target region via applying at least one sequence of electric voltage pulses between two electrodes 114 and 116 utilizing electrical signal generator 202. In an exemplary embodiment, electrical signal generator 202 may include an electrical pulse generator. In an exemplary embodiment, applying at least one sequence of electric voltage pulses between two electrodes 114 and 116 may include applying at least one sequence of eight square-wave electric voltage pulses with a magnitude in a range of about 500 V / cm to about 1500 V / cm and a duration of about 100 ps between two electrodes 114 and 116. In an exemplary embodiment, applying at least one sequence of electric voltage pulses between two electrodes 114 and 116 may include applying at least one sequence of eight square-wave electric voltage pulses with a magnitude of about 1000 V / cm and a duration of about 100 ps between two electrodes 114 and 116. In an exemplary embodiment, step 306 may further include generating an exemplary electric field all over an exemplary target region; allowing for electrical stimulation of all exemplary target cells therein.

[0065] In an exemplary embodiment, method 300 may be performed for a pre-determined period of time until a therapeutical target, for example, complete destruction of an exemplary plurality of cells including a plurality of cancer cells may be achieved. In an exemplary embodiment, an exemplary pre-determined period of time may depend on an exemplary therapeutical target. In an exemplary embodiment, an exemplary pre-determined period of time may depend on at least one of a location of an exemplary target region, size of an exemplary target region, an intensity of an exemplary generated electric field between two electrodes 114 and 116, and combinations thereof. In an exemplary embodiment, an exemplary predetermined period of time may include a continuous time interval or a plurality of intermittenttime intervals. In an exemplary embodiment, an exemplary pre-determined period of time may include an exemplary plurality of time steps. For instance, for ECT, treatment duration cannot be more than about 20 minutes in each treatment session due to a decrease in concentration of an applied chemotherapeutic in whole bloodstream.

[0066] In an exemplary embodiment, method 300 may further include a step of injecting a drug or a therapeutical substance from a reservoir embedded in variable-distance finger probe 100 or using an injection syringe into a location in the vicinity of an exemplary target region containing an exemplary plurality of target cells. In an exemplary embodiment, an exemplary injected drug or therapeutical substance may penetrate into an exemplary electrically stimulated plurality of target cells; thereby, resulting in treating an exemplary plurality of target cells.

[0067] In an exemplary embodiment, variable-distance finger probe 100 may be utilized for an electrical treatment of an exemplary plurality of target cells located in an exemplary target region of an exemplary living body (i.e., a human, or an animal), where an exemplary target region may be accessible only by an exemplary human’s fingers. In an exemplary embodiment, variable-distance finger probe 100 may be utilized for generating an electric field inside an exemplary target region between two electrodes 114 and 116; allowing for electrical stimulation of an exemplary target cells. In an exemplary embodiment, variable-distance finger probe 100 may be utilized for an exemplary electrical treatment of an exemplary plurality of target cells in an exemplary target region, where an invasive insertion of a needle-like electrode may not be allowed due to the sensitiveness of an exemplary target region. In such cases, an exemplary target region may be placed between plate-shaped electrodes 114 and 116 without any invasion utilizing variable-distance finger probe 100. Furthermore, variable-distance finger probe 100 may be utilized for an exemplary electrical treatment of an exemplary plurality of target cells in an exemplary target region, where an access there into is limited and an exemplary target region may be accessible only by an exemplary human’s fingers. In an exemplary embodiment, an exemplary electrical treatment of an exemplary plurality of target cells may include in-vivo electrically stimulation (e.g., electroporation or EChT) of an exemplary plurality of target cells. In an exemplary embodiment, two electrodes 114 and 116 may be utilized for transferring an electric field (e.g., a pulsed electric field or a DC electric field) from electrical signal generator 202 (e.g., an electrical pulse generator or a DC voltage generator) to an exemplary plurality of target cells while variable-distance finger probe 100 isput in contact with an exemplary target region. In an exemplary embodiment, variable -distance finger probe 100 may be put in contact with an exemplary target region via insertion of an exemplary human’s fingers into an exemplary living body in the vicinity of an exemplary target region. In an exemplary embodiment, variable-distance finger probe 100 may be placed at a hard to access part of an exemplary living body, where an exemplary hard to access part of an exemplary living body may include at least one of inside esophagus, surface of tracheal, behind bladder, anus entrance, narrow spaces inside at least one of digestive, respiratory, urogenital organs, or vessels, and combinations thereof.

[0068] In an exemplary embodiment, two electrodes 114 and 116 may be utilized for transferring (applying) an electrical signal (e.g., a pulsed electric field or a DC electric field) to an exemplary plurality of target cells to be treated via electrical stimulation (e.g., electroporation or EChT). In an exemplary embodiment, two electrodes 114 and 116 may be put in contact with a zone of at least one of a tissue, an organ, or a portion thereof including an exemplary plurality of target cells. In an exemplary embodiment, an electric potential may be applied between two electrodes 114 and 116 so that an exemplary electric field may be generated in an area including an exemplary plurality of target cells. In an exemplary embodiment, a pulsed electric field may be applied between two electrodes 114 and 116 and an exemplary pulsed electric field may be generated inside an exemplary zone including an exemplary plurality of target cells. In an exemplary embodiment, an exemplary plurality of target cells of at least one of an exemplary tissue, an exemplary organ, or an exemplary portion thereof may be affected by an exemplary electric field applied between two electrodes 114 and 116. In an exemplary embodiment, an exemplary plurality oftarget cells may be electroporated due to an exemplary electric field applied between two electrodes 114 and 116. In an exemplary embodiment, a DC electric field may be applied between two electrodes 114 and 116 and an exemplary DC electric field may be generated inside an exemplary zone including an exemplary plurality of target cells. In an exemplary embodiment, an exemplary plurality of target cells may be electrochemically stimulated via an EChT process due to an exemplary DC electric field applied between two electrodes 114 and 116.

[0069] In an exemplary embodiment, an exemplary target region may be swept and scanned by moving an exemplary human’s hand all over an exemplary target region and applying an exemplary electric field; thereby, resulting in electrically stimulating (e.g., electroporating or EChT) of all exemplary plurality of target cells. In an exemplary embodiment, a contactbetween two electrodes 114 and 116 and an exemplary target region may not need an insertion of two electrodes 114 and 116 into an exemplary target region and a superficial contact between two electrodes 114 and 116 and an exemplary target region may be effective for generating an exemplary electric field in an exemplary target region and electrically affecting exemplary plurality of target cells so that a completely non-invasive contact between two electrodes 114 and 116 and an exemplary target region, and consequently, a completely non-invasive electrically stimulation of an exemplary plurality of target cells may be achieved. In an exemplary embodiment, two electrodes 114 and 116 may be put over skin at a location adjacent to an exemplary target region. In another exemplary embodiment, two electrodes 114 and 116 may be put inside a person’s body at a location adjacent to an exemplary target region while a direct access to an exemplary target region being provided during a surgery.

[0070] FIG. 4 shows an example computer system 400 in which an embodiment of the present disclosure, or portions thereof, may be implemented as computer-readable code, consistent with one or more exemplary embodiments of the present disclosure. For example, computer system 400 may include an example of processing unit 204, and step 306 of flowchart presented in FIG. 3 may be implemented in computer system 400 using hardware, software, firmware, tangible computer readable media having instructions stored thereon, or a combination thereof and may be implemented in one or more computer systems or other processing systems. Hardware, software, or any combination of such may embody any of the modules and components in FIGs. 2 and 3.

[0071] If programmable logic is used, such logic may execute on a commercially available processing platform or a special purpose device. One ordinary skill in the art may appreciate that an embodiment of the disclosed subject matter can be practiced with various computer system configurations, including multi-core multiprocessor systems, minicomputers, mainframe computers, computers linked or clustered with distributed functions, as well as pervasive or miniature computers that may be embedded into virtually any device.

[0072] For instance, a computing device having at least one processor device and a memory may be used to implement the above-described embodiments. A processor device may be a single processor, a plurality of processors, or combinations thereof. Processor devices may have one or more processor “cores”.

[0073] An embodiment of the present disclosure is described in terms of this example computer system 400. After reading this description, it will become apparent to a person skilled in therelevant art how to implement the invention using other computer systems and / or computer architectures. Although operations may be described as a sequential process, some of the operations may in fact be performed in parallel, concurrently, and / or in a distributed environment, and with program code stored locally or remotely for access by single or multiprocessor machines. In addition, in some embodiments the order of operations may be rearranged without departing from the spirit of the disclosed subject matter.

[0074] Processor device 404 may be a special purpose or a general -purpose processor device. As will be appreciated by persons skilled in the relevant art, processor device 404 may also be a single processor in a multi-core / multiprocessor system, such system operating alone, or in a cluster of computing devices operating in a cluster or server farm. Processor device 404 may be connected to a communication infrastructure 406, for example, a bus, message queue, network, or multi-core message-passing scheme.

[0075] In an exemplary embodiment, computer system 400 may include a display interface 402, for example a video connector, to transfer data to a display unit 430, for example, a monitor. Computer system 400 may also include a main memory 408, for example, random access memory (RAM), and may also include a secondary memory 410. Secondary memory 410 may include, for example, a hard disk drive 412, and a removable storage drive 414. Removable storage drive 414 may include a floppy disk drive, a magnetic tape drive, an optical disk drive, a flash memory, or the like. Removable storage drive 414 may read from and / or write to a removable storage unit 418 in a well-known manner. Removable storage unit 418 may include a floppy disk, a magnetic tape, an optical disk, etc., which may be read by and written to by removable storage drive 414. As will be appreciated by persons skilled in the relevant art, removable storage unit 418 may include a computer usable storage medium having stored therein computer software and / or data.

[0076] In alternative embodiments, secondary memory 410 may include other similar means for allowing computer programs or other instructions to be loaded into computer system 400. Such means may include, for example, a removable storage unit 422 and an interface 420. Examples of such means may include a program cartridge and cartridge interface (such as that found in video game devices), a removable memory chip (such as an EPROM, or PROM) and associated socket, and other removable storage units 422 and interfaces 420 which allow software and data to be transferred from removable storage unit 422 to computer system 400.

[0077] Computer system 400 may also include a communications interface 424. Communications interface 424 allows software and data to be transferred between computer system 400 and external devices. Communications interface 424 may include a modem, a network interface (such as an Ethernet card), a communications port, a PCMCIA slot and card, or the like. Software and data transferred via communications interface 424 may be in the form of signals, which may be electronic, electromagnetic, optical, or other signals capable of being received by communications interface 424. These signals may be provided to communications interface 424 via a communications path 426. Communications path 426 carries signals and may be implemented using wire or cable, fiber optics, a phone line, a cellular phone link, an RF link or other communications channels.

[0078] In this document, the terms “computer program medium” and “computer usable medium” are used to generally refer to media such as removable storage unit 418, removable storage unit 422, and a hard disk installed in hard disk drive 412. Computer program medium and computer usable medium may also refer to memories, such as main memory 408 and secondary memory 410, which may be memory semiconductors (e.g. DRAMs, etc.).

[0079] Computer programs (also called computer control logic) are stored in main memory 508 and / or secondary memory 410. Computer programs may also be received via communications interface 424. Such computer programs, when executed, enable computer system 400 to implement different embodiments of the present disclosure as discussed herein. In particular, the computer programs, when executed, enable processor device 404 to implement the processes of the present disclosure, such as the operations in method 300 illustrated by FIG. 3, discussed above. Accordingly, such computer programs represent controllers of computer system 400. Where an exemplary embodiment of method 300 is implemented using software, the software may be stored in a computer program product and loaded into computer system 400 using removable storage drive 414, interface 420, and hard disk drive 412, or communications interface 424.

[0080] Embodiments of the present disclosure also may be directed to computer program products including software stored on any computer useable medium. Such software, when executed in one or more data processing device, causes a data processing device to operate as described herein. An embodiment of the present disclosure may employ any computer useable or readable medium. Examples of computer useable mediums include, but are not limited to, primary storage devices (e.g., any type of random access memory), secondary storage devices(e.g., hard drives, floppy disks, CD ROMS, ZIP disks, tapes, magnetic storage devices, and optical storage devices, MEMS, nanotechnological storage device, etc.).Industrial Applicability

[0081] Disclosed herein is a device, method, and system for electrical stimulation of target cells in a living body, particularly located at sensitive and / or difficult-to-access regions of an exemplary living body as well as systems and methods utilizing thereof. An exemplary device includes non-invasive structured electrodes capable of being placed in a hard to access target region or in the vicinity of an exemplary target region without causing bleeding, tearing, or any injuries. An exemplary device includes a finger probe fixed on a subject’s fingers (e.g., a surgeon’s fingers), and limited areas of a living body can be exposed to an electric field applied between electrodes of an exemplary finger probe by inserting or putting an exemplary subject’s fingers at / inside an exemplary target region. A distance between two electrodes of an exemplary finger probe is variable and can be adjusted by movements of an exemplary subject’s fingers so that an exemplary target region or a portion thereof may be encompassed between exemplary two electrodes of an exemplary finger probe; allowing for applying an effective electric field thereto.

[0082] For example, in some cancer cases, cancer cells are located in areas where no access thereto is possible using any electrodes (due to limited space). Herein, design of an exemplary finger probe makes it possible for exemplary electrodes to be effectively used in these cases. For example, in esophageal cancers, when the esophagus is released from the trachea and it is known that cancer has transferred from radial wall of the esophagus to the trachea and it is possible that it is infected on surface of the trachea, there is no access to the infected site in this area except a surgeon's finger. So, an appropriate way for electrochemotherapy in these areas is to use an exemplary finger probe. Another example is sarcoma or carcinoma that affects back of the bladder, which is adjacent to the abdominal area. Electrochemotherapy in this area is not possible using conventional methods because it is not possible to enter any electrode in this small space. Using an exemplary finger probe is a solution for electrochemotherapy of this area, because several fingers can be placed directly behind the bladder. In this case, back of the bladder can be scanned using a finger electrode and electrochemotherapy treatment can be applied. Another example is involvement of the anus in patients with rectal cancer. If there is a possibility of involvement of the rectum in the entrance of the anus and the lumen of this area, an exemplary finger probe can be used for electrochemotherapy of this area.

[0083] While the foregoing has described what are considered to be the best mode and / or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and that the teachings may be applied in numerous applications, only some of which have been described herein. It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.

[0084] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.

[0085] The scope of protection is limited solely by the claims that now follow. That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents. Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of Sections 101, 102, or 103 of the Patent Act, nor should they be interpreted in such a way. Any unintended embracement of such subject matter is hereby disclaimed.

[0086] Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.

[0087] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been set forth herein. Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions. The terms “comprises,” “comprising,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element proceeded by “a” or “an” does not,without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[0088] The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it can be seen that various features are grouped together in various implementations. This is for purposes of streamlining the disclosure, and is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter.

[0089] While various implementations have been described, the description is intended to be exemplary, rather than limiting and it will be apparent to those of ordinary skill in the art that many more implementations and implementations are possible that are within the scope of the implementations. Although many possible combinations of features are shown in the accompanying figures and discussed in this detailed description, many other combinations of the disclosed features are possible. Any feature of any implementation may be used in combination with or substituted for any other feature or element in any other implementation unless specifically restricted. Therefore, it will be understood that any of the features shown and / or discussed in the present disclosure may be implemented together in any suitable combination. Accordingly, the implementations are not to be restricted except in light of the attached claims and their equivalents. Also, various modifications and changes may be made within the scope of the attached claims.

Claims

What is claimed is:

1. A variable-distance finger probe for electrical stimulation of a target region of a living body, the variable -distance finger probe comprising: two pieces coupled together with an adjustable middle distance, each of the two pieces comprising at least one finger holder at a back side of the piece, each respective finger holder encompassing at least one different finger of one hand of an expert, respective front sides of the two pieces being located in front of each other with the adjustable middle distance; a distance-adjusting set located between the two pieces, the distance-adjusting set comprising: at least two springs located between the front sides of the two pieces, a length of each respective spring being adjustable by movements of the encompassed fingers of the expert; at least two shafts, each respective shaft passing through one spring of the at least two springs; at least one guide shaft located between the at least two shafts, the at least one guide shaft keeping the two pieces parallel with each other; and a base part attached to a respective front side of a first piece of the two pieces, the base part comprising three holes, the three holes receiving the at least two shafts and the at least one guide shaft passing there through, wherein each piece of the two pieces comprises three holes aligned with the three holes of the base part, the three holes of each respective piece receiving the at least two shafts and the at least one guide shaft passing there through, two ends of each shaft of the at least two shafts being fastened onto respective back sides of the two pieces; and two electrodes attached onto respective front sides of the two pieces in front of each other, each electrode of the two electrodes being connected to a different pole of two poles of an electrical signal generator.

2. The variable-distance finger probe of claim 1, wherein each electrode of the two electrodes comprises a biocompatible electrically conductive flat plate with a surface area in a range of 0.25 cm2to 10 cm2.

3. The variable-distance finger probe of claim 1, wherein each electrode of the two electrodes comprises a biocompatible electrically conductive flat plate with a thickness in a range of 1 mm to 5 mm.

4. The variable-distance finger probe of claim 1, wherein each spring of the at least two springs comprises a biocompatible spring with a variable length in a range of 0.5 cm to 2 cm.

5. The variable-distance finger probe of claim 1, wherein a distance between the two electrodes comprises an adjustable distance in a range of 0.5 cm to 2 cm by pressing or releasing the at least two springs via movements of the encompassed fingers of the expert.

6. The variable-distance finger probe of claim 1, wherein each piece of the two pieces comprises a piece of a biocompatible electrical insulator, the biocompatible electrical insulator comprising at least one of Teflon, polyethylene, polylactic acid, and combinations thereof.

7. The variable-distance finger probe of claim 1, wherein each electrode of the two electrodes is covered with a layer of at least one of silicone rubber, polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), and combinations thereof, a thickness of the layer being in a range of 100 nm to 1 pm.

8. The variable-distance finger probe of claim 1, wherein the at least one finger holder of the first piece comprises a first half-ring-shaped part protruded from the respective back side of the first piece, the first half-ring-shaped part configured to encompass thumb of the one hand of the expert.

9. The variable-distance finger probe of claim 8, wherein the at least one finger holder of the second piece comprises: a second half-ring-shaped part protruded from the respective back side of the second piece, the second half-ring-shaped part configured to encompass index finger of the one hand of the expert; and a third half-ring-shaped part protruded from the respective back side of the second piece next to the second half-ring-shaped part, the third half-ring-shaped part configured to encompass middle finger of the one hand of the expert.

10. The variable-distance finger probe of claim 1, further comprising two electrically conductive lines, each respective electrically conductive line comprising a distal end and a proximal end, the distal end being connected to one electrode of the two electrodes, the proximal end being connected to a pole of the two poles of the electrical signal generator.

11. A system for electrical stimulation of a target region of a living body, the system comprising: a variable-distance finger probe configured to transfer an electric field to the target region, the variable-distance finger probe being attached or mounted onto fingers of one hand of an expert and being put in the vicinity of the target region via insertion of the expert’s finger into the living body, the variable-distance finger probe comprising: two pieces coupled together with an adjustable middle distance, each of the two pieces comprising a piece of a biocompatible polymer comprising at least one finger holder at a back side of the piece, each respective finger holder encompassing at least one different finger of the one hand of the expert, respective front sides of the two pieces being located in front of each other with the adjustable middle distance; a distance-adjusting set located between the two pieces, the distanceadjusting set comprising: at least two springs located between the front sides of the two pieces, a length of each respective spring being adjustable by movements of the fingers of the expert; at least two shafts, each respective shaft passing through one spring of the at least two springs; at least one guide shaft located between the at least two shafts, the at least one guide shaft keeping the two pieces parallel with each other; and a base part attached to a respective front side of a first piece of the two pieces, the base part comprising three holes, the three holes receiving the at least two shafts and the at least one guide shaft passing there through,wherein each piece of the two pieces comprises three holes aligned with the three holes of the base part, the three holes of each respective piece receiving the at least two shafts and the at least one guide shaft passing there through, two ends of each shaft of the at least two shafts being fastened onto respective back sides of the two pieces; and two electrodes attached onto respective front sides of the two pieces in front of each other with the adjustable middle distance, an electrical signal generator configured to apply an electric field between the two electrodes, each electrode of the two electrodes being connected to a different pole of two poles of the electrical signal generator; and a processing unit electrically connected to the electrical signal generator, the processing unit comprising: a memory having processor-readable instructions stored therein; and a processor configured to access the memory and execute the processor- readable instructions, which, when executed by the processor configures the processor to perform a method, the method comprising: electrically stimulating a plurality of target cells in the target region by generating the electric field between the two electrodes inside the target region via applying an electric voltage between the two electrodes utilizing the electrical signal generator.

12. The system of claim 11, wherein each electrode of the two electrodes comprises a biocompatible electrically conductive flat plate with a surface area in a range of 0.25 cm2to 10 cm2and a thickness in a range of 1 mm to 5 mm.

13. The system of claim 11, wherein each spring of the at least two springs comprises a biocompatible spring with a variable length in a range of 0.5 cm to 2 cm.

14. The system of claim 11, wherein a distance between the two electrodes comprises an adjustable distance in a range of 0.5 cm to 2 cm by pressing or releasing the at least two springs via movements of the encompassed fingers of the expert.

15. The system of claim 11, wherein each piece of the two pieces comprises a piece of a biocompatible electrical insulator, the biocompatible electrical insulator comprising at least one of Teflon, polyethylene, polylactic acid, and combinations thereof.

16. The system of claim 11, wherein each electrode of the two electrodes is covered with a layer of at least one of silicone rubber, polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), and combinations thereof, a thickness of the layer being in a range of 100 nm to 1 pm.

17. The system of claim 11, wherein the at least one finger holder of the first piece comprises a first half-ring-shaped part protruded from the respective back side of the first piece, the first half-ring-shaped part configured to encompass thumb of the one hand of the expert.

18. The system of claim 17, wherein the at least one finger holder of the second piece comprises: a second half-ring-shaped part protruded from the respective back side of the second piece, the second half-ring-shaped part configured to encompass index finger of the one hand of the expert; and a third half-ring-shaped part protruded from the respective back side of the second piece next to the second half-ring-shaped part, the third half-ring-shaped part configured to encompass middle finger of the one hand of the expert.

19. The system of claim 11, wherein electrically stimulating the plurality of target cells comprises electroporating the plurality of target cells by applying at least one sequence of electric voltage pulses between the two electrodes, applying the at least one sequence of electric voltage pulses comprises applying at least one sequence of eight square-wave electric voltage pulses with a magnitude in a range of 500 V / cm to 1500 V / cm and a duration of 100 ps between the two electrodes, wherein the electrical signal generator comprises an electrical pulse generator.

20. The system of claim 11, wherein electrically stimulating the plurality of target cells comprises electrolyzing peripheral medium surrounding the plurality of target cells within a set of pre-determined time steps, the set of pre -determined time steps comprising at least oneof a set of equal time steps, a set of unequal time steps, and combinations thereof, each time step of the set of pre-determined time steps comprising a time period in a range between 1 minutes and 3 minutes, wherein the electrical signal generator comprises a DC voltage generator.

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