A cell status detection device based on a cellular electrochemical / electromechanical properties

Abstract

A detection device to detect a cell status comprises an actuating spot comprising at least two triangular electrodes and a detection spot comprising at least two coplanar electrodes. The actuating spot is mounted between the detection spot and configure to ensnare a cell via applying a first electric field and deform the cell via inducing a second electric field. Furthermore, the detection spot configure to determine a first cellular electrochemical property of the trapped cell as well as determine a second cellular electrochemical property of the deformed cell. If the first cellular electrochemical property quantity is equal to the second cellular electrochemical property quantity, the cell status is a cancer cell and if the first cellular electrochemical property quantity is higher than the second cellular electrochemical property quantity, the cell status is a normal cell.

Description

Ref-1403-02-8734A CELL STATUS DETECTION DEVICE BASED ON A CELLULAR ELECTROCHEMICAL / ELECTROMECHANICAL PROPERTIESTECHNICAL FIELD

[0001] The present disclosure generally relates to an exemplary detection device to obtain an exemplary cell status based on changes of an exemplary cellular electrochemical property due to cell deformation, and in particular an exemplary detection device comprising an exemplary actuating spot to trap a cell and deform the cell and an exemplary detection spot to detect a cell status (normal or cancer status of cell) based on the comparison of a trapped cell impedance and a deformed cell impedance.BACKGROUND

[0002] Cancer is a disease in which some cells of a specific body’s part uncontrollably grow and these cells maybe spread to other parts of the body. Early detection of cancer is one of the important aspects of cancer control and treatment. Therefore, in recent years, development of equipment and / or a methods that lead to early diagnosis of the cancer has been prioritized by various medical groups as well as researchers.

[0003] A cancer cell may undergoes many changes in various properties such as mechanical, chemical, electrical, and / or electrochemical, which researchers have used some of these changes and manufactured different detection devices to detect the cancer cells and / or detect the cell statue and differ a normal cell from a cancer cell. As mentioned-above, changes of the electromechanical property of a cell and converting theses changes to a measurable parameter such as an electrochemical property can be used to determine the cell status. Furthermore, a cell can show a change of the electromechanical property through a dielectrophoresis phenomenon, particularly a positive dielectrophoresis phenomenon. Although, complex and expensive equipment such asRef-1403-02-8734 imaging and image processing devices, which have their own errors, are needed in order to measure the electromechanical property changes of a cell.

[0004] On the other hand, one of the most widely used methods for analyzing the cell properties is an electrical impedance spectroscopy, especially an electrical impedance spectroscopy with the coplanar electrodes. However, the electrochemical impedance spectroscopy with the coplanar electrodes is highly dependent on a cell position, particularly, a cell height from a surface of the coplanar electrodes as a detection spot.

[0005] Thus, there is a need to engineer and develop a detection device to detect a cell status based on a electromechanical property of the cell which comprise an actuating spot to induce a change of the cell’s electromechanical property and a detection spot to detect the cell’s electromechanical property changes such that a detection device can determine the cell status without any dependency on a cell height.SUMMARY

[0006] This summary is intended to provide an overview of the subject matter of the present disclosure, and is not intended to identify essential elements or key elements of the subject matter, nor is it intended to be used to determine the scope of the claimed implementations. Its sole purpose is to present some concepts of one or more aspects in a simplified form as a prelude to the more detailed description that is presented later. The proper scope of the present disclosure may be ascertained from the claims set forth below in view of the detailed description below and the drawings.

[0007] One or more exemplary embodiments describe an exemplary detection device to detect an exemplary cell status. The exemplary detection device may comprise at least one exemplary actuating spot and at least one exemplary detection spot. In one or more exemplary embodiment, the at least one exemplary actuating spot may be mounted between the at least one exemplary detection spot. In an exemplary embodiment, the at least one exemplary actuating spotRef-1403-02-8734 may comprise at least two exemplary actuating electrodes which the at least two exemplary actuating electrodes may configure to ensnare an exemplary cell between the at least two exemplary actuating electrodes utilizing inducing an exemplary first noninvasive electric field as well as deform the exemplary trapped cell by inducing an exemplary second noninvasive electric field. In an exemplary embodiment, the at least one exemplary detection spot may comprise at least two exemplary coplanar pattern electrodes that the at least two exemplary coplanar pattern electrodes may configure to determine an exemplary first cellular electrochemical property and an exemplary second cellular electrochemical property. In one or more exemplary embodiments, the exemplary first cellular electrochemical property may be determined after inducing the exemplary first noninvasive electric field and the exemplary second cellular electrochemical property may be determined after inducing the exemplary second noninvasive electric field.

[0008] In one or more exemplary embodiments, the exemplary first and second cellular electrochemical properties may be an exemplary electrochemical impedance.

[0009] In one or more exemplary embodiments, an exemplary distance of each exemplary tip of the exemplary actuating electrodes from each exemplary coplanar pattern electrodes may be in an exemplary range of 10 pm to 30 pm. In one or more exemplary embodiments, an exemplary distance of each exemplary tip of the exemplary actuating electrodes from each exemplary coplanar electrodes may be equal. In one or more exemplary embodiments, an exemplary base’s width of each exemplary actuating electrodes may be in an exemplary range of 10 pm to 30 pm. In one or more exemplary embodiments, an exemplary distance of each exemplary tip of the exemplary actuating electrodes from each other may be in an exemplary range of 20 pm to 60 pm. In one or more exemplary embodiments, the at least two exemplary coplanar pattern electordes may have a rectangle pattern. In one or more exemplary embodiments, an exemplary rectangle’s width of each exemplary coplanar electrode may be in an exemplary rangeRef-1403-02-8734 of 50 m to 200 m and an exemplary rectangle’s length of each exemplary coplanar electrodes may be in an exemplary range of 70 pm to 100 pm.

[0010] In one or more exemplary embodiment, the exemplary detection device may further comprise an exemplary signal generator, an exemplary means for measuring a cellular electrochemical property quantity, and an exemplary programmable device.

[0011] In an exemplary embodiment, the exemplary means for creating a signal may configure to generate the exemplary first noninvasive electric field with an exemplary first predetermined signal as well as generate the exemplary second noninvasive electric field with an exemplary second predetermined signal. In one or more exemplary embodiments, the exemplary means for creating a signal may be connected to the at least two exemplary actuating electrodes utilizing an exemplary first conductive connector and an exemplary second conductive connector. In one or more exemplary embodiments, the exemplary first predetermined signal may comprise an exemplary frequency in an exemplary range of 500 KHz to 3000 KHz and an exemplary voltage in an exemplary range of 0.3 V to 1 V. In one or more exemplary embodiments, the exemplary second predetermined signal may comprise an exemplary frequency in an exemplary range of 500 KHz to 3000 KHz and an exemplary voltage in an exemplary range of 3 V to 14

[0012] In one or more exemplary embodiments, the exemplary means for measuring a cellular electrochemical property quantity may be connected to the at least two exemplary coplanar pattern electrodes utilizing an exemplary third conductive connector and an exemplary fourth conductive connector.

[0013] In one or more exemplary embodiment, the exemplary programmable device may comprise one or more processors, at least one memory, a computing program, and at least one connection port. In one or more exemplary embodiments, the exemplary programmable device may configure to analyze the exemplary received data from the exemplary means for measuring the cellular electrochemical property quantity and specifying the exemplary cell status based onRef-1403-02-8734 the analyzed data such that if the exemplary first cellular electrochemical property is equal to the exemplary second cellular electrochemical property, the exemplary cell status is a cancer cell and if the exemplary first cellular electrochemical property is higher than the exemplary second cellular electrochemical property, the exemplary cell status is a normal cell.

[0014] This Summary may introduce a number of concepts in a simplified format; the concepts are further disclosed within the “Detailed Description” section. This Summary is not intended to configure essential / key features of the claimed subject matter, nor is intended to limit the scope of the claimed subject matter.BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The novel features which are believed to be characteristic of the present disclosure, as to its structure, organization, use and method of operation, together with further objectives and advantages thereof, will be better understood from the following drawings in which a presently preferred embodiment of the present disclosure will now be illustrated by way of example. It is expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the present disclosure. Embodiments of the present disclosure will now be described by way of example in association with the accompanying drawings in which:

[0016] FIG.1A illustrates an exemplary block diagram of an exemplary detection device to detect an exemplary cell status, consistent with one or more exemplary embodiments of the present disclosure;

[0017] FIG.1B illustrates an exemplary block diagram of an exemplary detection device comprising an exemplary trapped cell, consistent with one or more exemplary embodiments of the present disclosure;Ref-1403-02-8734

[0018] FIG.1C illustrates an exemplary block diagram of an exemplary detection device comprising an exemplary deformed cell, consistent with one or more exemplary embodiments of the present disclosure;

[0019] FIG.2 an exemplary flowchart of an exemplary use method of an exemplary detection device for detecting an exemplary cell status, consistent with one or more exemplary embodiments of the present discloser;

[0020] FIG.3 illustrates an exemplary plot of impedance spectra of an exemplary single breast MCF-10A cell after (a) inducing the exemplary first positive dielectrophoresis and (b) inducing the exemplary second positive dielectrophoresis, consistent with one or more exemplary embodiments of the present disclosure;

[0021] FIG.4A illustrates an exemplary light microscope image of an exemplary trapped single breast MCF-10A cell after inducing an exemplary first positive dielectrophoresis, consistent with one or more exemplary embodiments of the present disclosure;

[0022] FIG.4B illustrates an exemplary light microscope image of an exemplary deformed single breast MCF-10A cell after inducing an exemplary second positive dielectrophoresis, consistent with one or more exemplary embodiments of the present disclosure; and

[0023] FIG.5 illustrates an exemplary plot of impedance spectra of (a) an exemplary single pancreas cell (PANC-1) after inducing a first positive dielectrophoresis and (b) an exemplary single pancreas cell after inducing a second positive dielectrophoresis, consistent with one or more exemplary embodiments of the present disclosure.DETAILED DESCRIPTION

[0024] In the following detailed description, numerous specific details are set forth by way of examples to provide a thorough understanding of the relevant teachings related to the exemplary embodiments. 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 circuitryRef-1403-02-8734 have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

[0025] The following detailed description is presented to enable a person skilled in the art to make and use the methods and devices disclosed in one or more exemplary embodiments of the present disclosure. For purposes of explanation, specific nomenclature is set forth to provide a thorough understanding of the present disclosure. However, it will be apparent to one skilled in the art that these specific details are not required to practice the disclosed exemplary embodiments. Descriptions of specific exemplary embodiments are provided only as representative examples. Various modifications to the exemplary implementations will be plain to one skilled in the art, and the general principles defined herein may be applied to other implementations and applications without departing from the scope of the present disclosure. The present disclosure is not intended to be limited to the implementations shown, but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

[0026] Disclosed herein is an exemplary detection device to detect an exemplary cell status. In an exemplary embodiment, “detection device” may refer to an exemplary apparatus that can create an exemplary measurable response to an exemplary changes of an exemplary cell’s property. In an exemplar embodiment, “cell’s property” may refer to an exemplary electromechanical property. Some benefits from utilizing an exemplary detection device described within the present disclosure may include, but are not limited to, an easy-to-use and cost-effective detection device that is capable of determining an exemplary normal cell and / or an exemplary cancerous cell, independency to an exemplary cell position, increasing an exemplary detection speed, no need to imaging equipment as well as image processing equipment, no need to collect additional information to specify an exemplary cell's status, simultaneous evaluation of electrochemical and electromechanical properties of the cell, etc.Ref-1403-02-8734

[0027] In an exemplary embodiment, an exemplary detection device may comprise at least two main parts that can detect an exemplary cell status. In an exemplary embodiment, “cell status” may refer to an exemplary status that can obtain whether an exemplary cell is an exemplary normal cell or an exemplary cancer cell. In an exemplary embodiment, “cancer cell” may refer to an exemplary plurality of cells that indicates an exemplary abnormal growth, proliferation, and the like that also can spread to other parts of the body. In an exemplary embodiment, at least two main parts may comprise an exemplary actuating spot and an exemplary detection spot. In an exemplary embodiment, “actuating spot” may refer to an exemplary structure that can induce an exemplary cell’s property changes by applying an exemplary external driving force. In an exemplary embodiment, “detection spot” may refer to an exemplary structure that can measure the cell’s property changes induced by an exemplary actuating spot.

[0028] In an exemplary embodiment, an exemplary detection device may comprise at least one exemplary actuating spot and at least one exemplary detection spot such that at least one exemplary actuating spot may comprise at least two exemplary actuating electrodes and at least one exemplary detection spot may comprise at least two exemplary coplanar electrodes.

[0029] In one or more exemplary embodiment, an exemplary two actuating electrodes may have a pattern comprising, for example, but is not limited, an exemplary triangular pattern, and exemplary elliptical pattern, or a combination thereof.

[0030] Referring to the figures, FIG.1A illustrates an exemplary block diagram of an exemplary detection device 100 to detect an exemplary cell status, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, in further detail with respect to FIG.1A, the exemplary detection device 100 may comprise at least one exemplary actuating spot 102 and at least one detection spot 104. In one or more exemplary embodiments, the at least one actuating spot 102 may comprise at least two triangular electrodes (102a and 102b, respectively) that the actuating spot 102 may configure to ensnare an exemplary cell and deformRef-1403-02-8734 the exemplary trapped cell. In one or more exemplary embodiments, the at least one exemplary detection spot 104 may comprise at least two exemplary coplanar electrodes (104a and 104b, respectively) that the detection spot 104 may configure to determine an exemplary cellular electrochemical property of the exemplary trapped cell as well as an exemplary cellular electrochemical property of the exemplary deformed cell.

[0031] In one or more exemplary embodiments, the exemplary actuation spot 102 and the exemplary detection spot 104 may be prepared utilizing an exemplary printing process. In an exemplary embodiment, an exemplary lithography process, for example, but is not limited to, an exemplary photolithography, may be used to create the at least two triangular electrodes 102a, 102b of the exemplary actuation spot 102 and the at least two exemplary coplanar electrodes 104a, 104b of the exemplary detection spot 104. In an exemplary embodiment, an exemplary conductive metal, for exemplar, but are not limited to, gold, copper, platinum, indium tin oxide, titanium, carbon based materials such as graphene, carbon nanotubes, or a combination thereof, silicon based materials such as silicon dioxide, silicon nitride, and / or a combination thereof, metallized silicon such as silicon subtstrates coated with at least one conductive metal such as gold, platinium, titanium, and / or a combination thereof, and / or a combination thereof, may be used to fabricate the exemplary two triangular 102a, 102b and coplanar 104a, 104b electrodes. In one or more exemplary embodiments, the exemplary two triangular 102a, 102b and coplanar 104a, 104b electrodes may be fabricated on an exemplary substrate utilizing the exemplary lithography process. In these exemplary embodiments, an exemplary passive layer may be applied to an exemplary area of the exemplary substrate such that the exemplary passive layer can cover the exemplary area of the exemplary substrate that is not involved in the exemplary actuating spot 102 and the exemplary detection spot 104.

[0032] In one or more exemplary embodiments, as illustrated in FIG.l,the exemplary actuating spots 102 comprising the at least two exemplary triangular electrodes 102a, 102b mayRef-1403-02-8734 be mounted between the at least two exemplary coplanar electrodes 104b, 104b of the exemplary detection spot 104. In an exemplary embodiment, an exemplary distance of the at least two exemplary triangular electrodes 102a, 102b may be equal from each of the at least two exemplary coplanar electrodes 104a, 104b. In one or more exemplary embodiments, an exemplary distance of each tip (illustrated as a letter of “di” in FIG.1A) of the exemplary triangular electrodes 102a, 102b may be adjusted in an exemplary range of 10 pm to 30 pm from the at least two exemplary coplanar electrodes 104a, 104b.

[0033] In one or more exemplary embodiments, referring to FIG.1A, an exemplary distance of each tip of the triangular electrodes 102a, 102b from each other (illustrated as a letter of “d2” in FIG.1A) may be adjusted in an exemplary range of 20 pm to 60 pm. In one or more exemplary embodiment, the exemplary cell can be ensnared and deformed at di by inducing an exemplary electric field with different voltages, respectively. In one or more exemplary embodiments, an exemplary base’s width of each exemplary triangular electrodes 102a, 102b may be in an exemplary range of 10 pm to 30 pm.

[0034] In one or more exemplary embodiment, in further detail with respect to FIGs.lA, the at least two exemplary coplanar electrodes 104a, 104b may have an exemplary rectangle pattern. In one or more exemplary embodiments, the at least two exemplary coplanar electors 104a, 104b may have an exemplary rectangle’s width in an exemplary range of 50 pm to 200 pm and an exemplary rectangle’s length in an exemplary range of 70 pm to 100 pm.

[0035] Referring to figures, FIG.1B and FIG.1C illustrate an exemplary block diagram of the exemplary detection device 100 comprising an exemplary trapped cell 120 and an exemplary deformed cell 122, respectively, consistent with one or more exemplary embodiments of the present disclosure. In one or more exemplary embodiments, as illustrated in FIGs.lB-C, the exemplary cell may be trapped between the exemplary two triangular electrodes 102a, 102b through inducing an exemplary first electric field and the exemplary trapped cell 120 may beRef-1403-02-8734 deformed through applying an exemplary second electric field utilizing the exemplary two triangular electrodes 102a, 102b. In an exemplary embodiment, the electric field can be a noninvasive electric field that can prevent any damage to the exemplary cell whether in the trapped or deformed statuses.

[0036] In an exemplary embodiment, in further detail with respect to FIGs.lA-C, the exemplary detection device 100 may further comprise an exemplary means for creating a signal 106 that may configure to generate an exemplary predetermined signal for forging an exemplary electric field. In one or more exemplary embodiments, the exemplary means for creating a signal 106 may be connected to each of at least two exemplary triangular electrodes 120a, 102b utilizing an exemplary first 110 and an exemplary second 112 conductive connectors. In one or more exemplary embodiments, the exemplary means for creating a signal 106 may generate the exemplary first electric field through generating an exemplary first predetermined signal which the first predetermined signal may comprise an exemplary first frequency and an exemplary first voltage in an exemplary range of 500 KHz to 3000 KHz and 0.3 V to 1 V, respectively. In one or more exemplary embodiments, the second electric field for deforming the exemplary trapped cell 120 may be generated utilizing the exemplary means for creating a signal 106 through generating an exemplary second predetermined signal that may comprise an exemplary second frequency in an exemplary range of 500 KHz to 3000 KHz and an exemplary second voltage in an exemplary range of 3 V to 14 V.

[0037] In one or more exemplary embodiment, the exemplary first electric field and the exemplary second electric field to ensnare and deform the exemplary cell, respectively, may be an exemplary dielectrophoresis, more particularly an exemplary positive dielectrophoresis.

[0038] In an exemplary embodiment, the exemplary means for creating a signal 106 may be, for example, but is not limited to, an exemplary signal generator, an exemplary function generator, and / or other kinds of means for creating a signal that are well known for those skilled in the art.Ref-1403-02-8734

[0039] In an exemplary embodiment, in further detail with respect to FIGs.lA-C, the exemplary detection device 100 may further comprise an exemplary means for measuring a cellular electrochemical property quantity 108. In one or more exemplary embodiments, the exemplary means for measuring a cellular electrochemical property quantity 108 may be connected to each of the exemplary coplanar electrodes 104a, 104b of the exemplary detection spot 104 utilizing an exemplary third conductive connectors 114 and an exemplary fourth conductive connector 116, respectively.

[0040] In an exemplary embodiment, in further detail with respect to FIGs.lA-C, the exemplary detection device 100 may further comprise an exemplary programmable device 118. The exemplary programmable device may comprise one or more exemplary processor, at least one exemplary memory, an exemplary computing program, and at least one exemplary connection port. In one or more exemplary embodiments, as illustrated in FIGs.lA-C, the exemplary programmable device 118 may be connected to the exemplary means for measuring a cellular electrochemical property quantity 108 utilizing at least one exemplary connection port (not shown). In one or more exemplary embodiments, the exemplary programmable device 118 may analyze an exemplary received data from the means for measuring the cellular electrochemical property quantity 100 when the cell exemplary trapped 120 between the at least two exemplary triangular electrodes 102a, 102b as well as an exemplary received data from the means for measuring the cellular electrochemical property quantity 100 when the cell exemplary deformed 122 between the at least two exemplary triangular electrodes 102a, 102b utilizing the exemplary computing program to specify the exemplary status of cell. In one or more exemplary embodiments, if an exemplary cellular electrochemical property quantity of the exemplary the trapped cell 120 is higher than an exemplary cellular electrochemical property quantity of the exemplary deformed cell 122, the cell status is a normal cell. In one or more exemplary embodiments, if an exemplary cellular electrochemical property quantity of the exemplaryRef-1403-02-8734 deformed cell 122 is same as an exemplary cellular electrochemical property quantity of the trapped cell 120, the cell status is a cancer cell. In an exemplary embodiment, the exemplary programmable device 118 can be a PC, a lab top, a smart phone, a tablet, and / or other programmable devices that are well known for those skilled in the art.

[0041] In one or more exemplary embodiments, the exemplary first and second cellular electrochemical property can be an exemplary electrical impedance. In one or more exemplary embodiments, the exemplary first cellular electrochemical property quantity and the second cellular electrochemical property quantity can be record as an exemplary first impedance spectra and an exemplary second impedance spectra, respectively. In one or more exemplary embodiments, an exemplary potentiostat or impedance analyzer may be used to record the exemplary first and second impedance spectra.

[0042] Furthermore, disclosed herein is an exemplary use method of and exemplary detection device to determine the exemplary cell status in accordance with one or more exemplary embodiments of the present disclosure.

[0043] FIG.2 illustrates an exemplary flowchart of an exemplary use method 200 of the exemplary detection device 100 for detecting an exemplary cell status, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiments, as illustrated in FIG.2, the exemplary use method 200 may comprise ten main steps. In first step (202), an exemplary buffer-cell containing solution may pour on the exemplary actuating spot 102. In next step (204), the exemplary first non-invasive electric field may be generated utilizing the exemplary means for creating a signal 106 and applied to ensnare the exemplary cell of the exemplary buffercell containing solution utilizing the at least two exemplary triangular electrodes 102a, 102b. Furthermore, the at least two exemplary coplanar pattern electrodes 104a, 104b may determine the exemplary first cellular electrochemical property of the exemplary trapped cell 120 (206) and the exemplary means for measuring a cellular electrochemical property quantity 108 may convertRef-1403-02-8734 the exemplary determined first cellular electrochemical property to the exemplary first cellular electrochemical property quantity 208. Step 210 may comprise saving the first exemplary cellular electrochemical property quantity on the at least one exemplary memory of the exemplary programmable device 118. In next step (212), the exemplary means for creating a signal 106 may generate the exemplary second noninvasive electric field and applied the exemplary second noninvasive electric field on the exemplary trapped cell 120 to obtain the exemplary deformed cell 122 utilizing the at least two exemplary triangular electrodesl02a,102b. Steps 214 and 216 may comprise determining the exemplary second cellular electrochemical property utilizing the at least two coplanar pattern electrodes 104a, 104b and converting the exemplary determined second cellular electrochemical property to the exemplary second cellular electrochemical property quantity utilizing the exemplary means for measuring a cellular electrochemical property quantity 108, respectively. Next step 218 may comprise saving the exemplary second cellular electrochemical property quantity on the at least one exemplary memory of the exemplary programmable device 118. In final step (220), the exemplary first and the exemplary second cellular electrochemical property quantities may be analyzed and compared utilizing the computing program of the programmable device 118 to specify the exemplary cell statue such that if the exemplary first cellular electrochemical property quantity is equal to the exemplary second cellular electrochemical property quantity, the cell status is an exemplary cancer cell 2022 and if the exemplary first cellular electrochemical property quantity is higher than the exemplary second cellular electrochemical property quantity, the cell status is an exemplary normal cell 2024.EXAMPLES

[0044] Hereinafter, one or more exemplary embodiments will be described in further detail with reference to examples. It will be obvious to a person having ordinary skill in the art that these examples may be for illustrative purposes only and are not to be interpreted to limit the scope of the present disclosure.Ref-1403-02-8734

[0045] Example 1: Detecting Breast MCF-10A Cells Status Utilizing A Detection Device

[0046] In this example, exemplary cell status of the exemplary breast MCF-10A cell was detect utilizing the exemplary detection device 100 based on an exemplary process similar to use method 200 of the exemplary detection device 100. To detecting the cell status of the exemplary breast MCF-10A cell, first an exemplary solution containing the exemplary breast MCF-10A cell and an exemplary buffer were poured on the exemplary actuating spot 102. Then, an exemplary first positive dielectrophoresis including an exemplary frequency in a range of 500 KHz to 3000 KHz and an exemplary voltage in a range of 0.3 V to 1 V was induced to the exemplary solution utilizing the at least two exemplary triangular electrodes 102a, 102b resulted in trapping an exemplary single breast MCF-10A cell between the at least two exemplary triangular electrodes 102a, 102b (FIG.3). Afterward, an exemplary first impedance spectra of the trapped single breast MCF-10A cell was recorded utilizing the exemplary means for measuring the cellular electrochemical property 108. Then, an exemplary second positive dielectrophoresis including an exemplary frequency in a range of 500 KHz to 3000 KHz and an exemplary voltage in a range of 3 V to 14 V was induced to the exemplary trapped single breast MCF-10A cell utilizing the at least two exemplary triangular electrodes 102a, 102b to deform the exemplary trapped single breast MCF-10A cell. Following that, an exemplary second impedance spectra of the exemplary deformed single breast MCF-10A cell was recorded utilizing the exemplary means for measuring the cellular electrochemical property 108. The first and second impedance spectra were analyzed utilizing the exemplary programmable device 108 to specify the cell status of the single breast MCF-10A cell.

[0047] FIG.3 illustrates an exemplary plot of impedance spectra of (a) an exemplary single breast MCF-10A cell after inducing the exemplary first positive dielectrophoresis and (b) the exemplary single breast MCF-10A cell after inducing the exemplary second positiveRef-1403-02-8734 dielectrophoresis, consistent with one or more exemplary embodiments of the present disclosure. Furthermore, FIG.4A and FIG.4B illustrate exemplary light microscope images of an exemplary trapped single breast MCF-10A cell 402 after inducing the exemplary first positive dielectrophoresis and an exemplary deformed single breast MCF-10A cell 404 after inducing the exemplary second positive dielectrophoresis, respectively, consistent with one or more exemplary embodiments of the present disclosure. As the results indicates, the exemplary impedance of the single breast MCF-10A cell was decrease after inducing the exemplary second positive dielectrophrosis compared to the exemplary impedance of single breast MCF-10A cell after inducing the exemplary first positive dielectrophrosis. When a cell was deformed in the exemplary actuating spot 102, the cell occupies more space resulted in a reduction in the exemplary impedance. Therefore, this reduction confirms the deformation of the single breast MCF-10A cell as well as the single breast MCF-10A cell is a normal cell.

[0048] Example 2: Detecting Pancreas Cell Status Utilizing A Detection Device

[0049] In this example, exemplary cell status of an exemplary pancreas cell was detect utilizing the exemplary detection device 100 based on an exemplary process similar to use method 200 of the exemplary detection device 100. To detecting the cell status of the exemplary pancreas cell, first an exemplary solution containing the exemplary pancreas cell and an exemplary buffer were poured on the exemplary actuating spot 102. Then, an exemplary first positive dielectrophoresis including an exemplary frequency in a range of 500 KHz to 3000 KHz and an exemplary voltage in a range of 0.3 V to 1 V was induced to the exemplary solution utilizing the at least two exemplary triangular electrodes 102a, 102b resulted in trapping an exemplary single pancreas cell between the at least two exemplary triangular electrodes 102a, 102b (FIG.3). Afterward, an exemplary first impedance spectra of the trapped single pancreas cell was recorded utilizing the exemplary means for measuring the cellular electrochemical property 108. Then, an exemplary second positive dielectrophoresis including an exemplary frequency in a range of 500Ref-1403-02-8734KHz to 3000 KHz and an exemplary voltage in a range of 3 V to 14 V was induced to the exemplary trapped single pancreas cell utilizing the at least two exemplary triangular electrodes 102a, 102b to deform the exemplary trapped single pancreas cell. Following that, an exemplary second impedance spectra of the exemplary deformed single pancreas cell was recorded utilizing the exemplary means for measuring the cellular electrochemical property quantity 108. The first and second impedance spectra were analyzed utilizing the exemplary programmable device 108 to specify the cell status of the single pancreas cell.

[0050] FIG.5 illustrates an exemplary plot of impedance spectra of (a) an exemplary single pancreas cell after inducing the exemplary first positive dielectrophoresis and (b) the exemplary single pancreas cell after inducing the exemplary second positive dielectrophoresis, consistent with one or more exemplary embodiments of the present disclosure. As the results indicates, the exemplary impedance spectra of the single pancreas cell after inducing the exemplary first positive dielectrophoresis indicated a same trend and impedance quantity compared to the exemplary impedance spectra of the single pancreas cell after inducing the exemplary second positive dielectrophoresis. These results confirm that the single pancreas cell status is a cancer cell.

[0051] 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.

[0052] 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.Ref-1403-02-8734

[0053] 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.

[0054] 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.

[0055] 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. 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.

[0056] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, 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.

[0057] 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 correspondingRef-1403-02-8734 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.

[0058] 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 may 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.

[0059] 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

Ref- 1403-02-8734What is claimed is:

1.

1. A detection device to detect a cell status comprising at least one actuating spot configure to ensnare a cell utilizing inducing a first electric field and deform a cell utilizing a second electric field, respectively; and at least one detection spot configure to determine a cellular electrochemical property of the cell in a trapped state and a deformed state, respectively, wherein: if the cellular electrochemical property of the trapped state is equal to the cellular electrochemical property of the deformed state, the cell status is a cancer cell, and if the cellular electrochemical property of the trapped state is higher than the cellular electrochemical property of the deformed state, the cell status is a normal cell.

2. The detection device of claim 1, wherein the actuating spot comprises at least two actuating electrodes, or wherein the cell is ensnared between the at least two actuating electrodes by inducing the first electric field and deformed by inducing the second electric field.

3. The detection device of claim 2, wherein a shape of the at least two actuating electrodes comprises a triangular pattern, a elliptical pattern, or a combination thereof.

4. The detection device of claim 1 , wherein the detection spot comprises at least two coplanar pattern electrodes.

5. The detection device of claim 1, wherein the at least one actuating spot is mounted between the at least one detection spot.

6. The detection device of claim 1, wherein the cellular electrochemical property is an electrochemical impedance.

7. The detection device of claim 1, wherein the first and the second electric field is a positive dielectrophoresis .Ref- 1403-02-87348. The detection device of claim 1 or 7, wherein the first electric filed has a frequency of 500 KHz to 3000 KHz and a voltage of 0.3 V to 1 V and the second electric field has a frequency of 500 KHz to 3000 KHz and a voltage of 3 V to 14 V.

9. The detection device of claim 1, further comprising a means for creating a signal configure to generate the first electric field and the second electric field wherein the means for creating a signal is connected to the actuating spot; a means for measuring a cellular electrochemical property quantity wherein the means for measuring the cellular electrochemical property quantity is connected to at the detection spot; and a programmable device configure to analyze the received data from the means for measuring the cellular electrochemical property quantity and specifying the cell status based on the analyzed data, wherein the programmable device comprises one or more processors, at least one memory, a computing program, and at least one connection port.

10. A detection device to detect a cell status comprising at least one actuating spot comprising at least two triangular pattern electrodes configure to ensnare a cell between the at least two actuating electrodes by inducing a first noninvasive electric field and deform the trapped cell by inducing a second noninvasive electric field; at least one detection spot comprising at least two coplanar pattern electrodes configure to determine a first cellular electrochemical property and a second cellular electrochemical property, wherein the first cellular electrochemical property is determined after inducing the first noninvasive electric field and the second cellular electrochemical property is determined after inducing the second noninvasive electric field;Ref- 1403-02-8734 a means for creating a signal configure to generate the first noninvasive electric field with a first predetermined signal and the second noninvasive electric field with a second predetermined signal, wherein the means for creating a signal is connected to the at least two actuating electrodes utilizing a first conductive connector and a second conductive connector; a means for measuring a cellular electrochemical property quantity configure to measure a first cellular electrochemical property quantiy and a second cellular electrochemical property aquantity wherein the means for measuring the cellular electrochemical property quantity is connected to at least two coplanar pattern electrodes utilizing a third conductive connector and a fourth conductive connector; and a programmable device configure to analyze the received data from the means for measuring the cellular electrochemical property quantity and specifying the cell status based on the analyzed data, wherein the programmable device comprises one or more processors, at least one memory, a computing program, and at least one connection port, wherein: if the first cellular electrochemical property quantity is equal to the second cellular electrochemical property quantity, the cell status is a cancer cell, and if the first cellular electrochemical property quantity is higher than the second cellular electrochemical property quantity, the cell status is a normal cell.

11. The detection device of claim 10, wherein the at least one actuating spot is mounted between the at least two coplanar pattern electrodes.

12. The detection device of claim 10, wherein the first cellular electrochemical property and the second cellular electrochemical property is an electrochemical impedance.

13. The detection device of claim 11, wherein a distance of each tip of the triangular pattern electrodes of the actuating spot from each coplanar pattern electrodes is in a range of 10 pm to 30 pm.Ref- 1403-02-873414. The detection device of claim 12, wherein a distance of each tip of triangular pattern electrodes from each coplanar electrodes is equal.

15. The detection device of claim 10, wherein a base’s width of each triangular pattern electrodes is in a range of 10 pm to 30 pm.

16. The detection device of claim 10 or 12, wherein a distance of each tip of the triangular pattern electrodes from each other is in a range of 20 pm to 60 pm.

17. The detection device of claim 10, wherein the at least two coplanar pattern electors has a rectangle pattern wherein a rectangle’s width of each coplanar electrode is in a range of 50 pm to 200 pm and a rectangle’s length of each coplanar electros is in a range of 70 pm to 100 pm.

18. The detection device of claim 10, wherein the first predetermined signal comprises a frequency in a range of 500 KHz to 3000 KHz and a voltage in a range of 0.3 V to 1 V.

19. The detection device of claim 10 or 18, wherein the second predetermined signal comprises a frequency in a range of 500 KHz to 3000 KHz and a voltage in a range of 3 V to 14 V.

20. A use method of a detection device of any claims of 10 to 19 comprising following steps: pouring a buffer-cell containing solution on the actuating spot; applying the first noninvasive electric field on the buffer-cell containing solution utilizing the at least two triangular electrodes and the signal generator; determining the first cellular electrochemical property utilizing the at least two coplanar pattern electrodes; converting the determined first cellular electrochemical property to a first cellular electrochemical property quantity utilizing the means for measuring the cellular electrochemical property quantity; saving the first cellular electrochemical property quantity on the at least one memory of the programmable device; applying the second noninvasive electric field on the buffer-cell containing solution utilizing the at least two triangular electrodes and the signal generator;Ref- 1403-02-8734 determining the second cellular electrochemical property utilizing the at least two coplanar pattern electrodes; converting the determined second cellular electrochemical property to a second cellular electrochemical property quantity utilizing the means for measuring the cellular electrochemical property quantity; saving the second cellular electrochemical property quantity on the at least one memory of the programmable device; and analyzing the first and the second cellular electrochemical property quantity and comparing the first and the second cellular electrochemical property quantity utilizing the computing program of the programmable device, wherein: if the first cellular electrochemical property quantity is equal to the second cellular electrochemical property quantity, the cell status is a cancer cell, and if the first cellular electrochemical property quantity is higher than the second cellular electrochemical property quantity, the cell status is a normal cell.

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