Apparatus and method for isolating single-stranded DNA analyte material from a biological sample for analysis using a sensor device - Patent Application 20070122999

Abstract

A device for transferring charged molecules between a first solution compartment and a second solution compartment includes: a barrier disposed between the first solution compartment and the second solution compartment; a valve configured within the barrier; and a plurality of electrets within at least one of the first solution compartment and the second solution compartment, the plurality of electrets being sized and shaped to cause the charged molecules to accumulate in a focal zone on the first solution compartment side of the valve. The valve may include a cavity within the valve for receiving the charged molecules, and rotation of the cavity relative to the barrier causes delivery of the charged molecules within the cavity from the first solution compartment side of the valve to the second solution compartment side of the valve. The valve may be made of a conductive material and may include a conductive extension on the opposite side of the cavity.

Description

[Technical Field]

[0001] Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 428,087, filed November 27, 2022, entitled "Passive Sensor Capable of Detecting Materials Containing Specific DNA or DNA-Like Strands," and U.S. Provisional Patent Application No. 63 / 435,258, filed December 25, 2022, entitled "Passive Sensor Capable of Detecting Materials Containing Specific DNA or DNA-Like Strands," the contents of which are incorporated by reference as if fully set forth herein.

[0002] FIELD OF THE INVENTION The present invention relates to the sensing of biomolecules and DNA-like molecules. In particular, the present invention relates to multi-chamber implementations of such sensor devices. More specifically, the present invention relates to an apparatus and method for transferring material from a biological sample between adjacent compartments, each compartment having a different solution for acting on the biological sample and isolating single-stranded DNA from the biological sample, allowing for examination of the isolated DNA strands. [Background technology]

[0003] Background of the Invention Various methods are available for detecting RNA, DNA, or DNA-like molecules. These methods include gel electrophoresis and binding of DNA to DNA-specific fluorescent dyes. These methods generally require transport of samples to laboratories with dedicated equipment and highly skilled personnel. These methods are inefficient and too expensive to be useful on a large scale.

[0004] As personalized treatments for people with specific DNA sequences or microbiomes are developed, detecting specific DNA or DNA-like sequences is becoming increasingly desirable. For example, capabilities are being developed that allow matching an individual's genomic profile and microbiome with the food or cosmetic products that are most suitable for that individual.

[0005] Therefore, there is a need for a simple, low-cost, disposable passive sensor for detecting cDNA / DNA / RNA-like molecules that does not require an internal power source.

[0006] Furthermore, there is a need for an implementation of this sensor that is low cost, easy to manufacture, and relies on passive principles to isolate cDNA / DNA / RNA-like molecules from the biological sample from which they were obtained. Summary of the Invention

[0007] The present disclosure teaches a sensor capable of performing testing of materials in general, and RNA / DNA / DNA-like molecules in particular, without involving highly trained and costly personnel using expensive laboratory equipment. The sensor is simple, inexpensive, and disposable. Furthermore, the sensor does not require an on-sensor power supply, complex electronic microchips, microprocessors, multiplexers, or complex transceivers. The sensor may be implemented in the fields of microbiome and personalized beauty, among other things, to enable matching of an individual's genomic characteristics or their microbiome with the food or cosmetic products most suited to that individual.

[0008] In particular, the present invention teaches a sensor consisting of multiple adjacent compartments, each containing a different solution that may ultimately function to degrade biological material into single-stranded DNA samples. Valves are configured between the compartments that operate to transport the DNA strands of interest to the next compartment while leaving unwanted biological material in the preceding compartment.

[0009] According to a first aspect, a device for transferring charged molecules between a first solution compartment and a second solution compartment is disclosed, the device including: a barrier disposed between the first solution compartment and the second solution compartment; a valve configured within the barrier; and a plurality of electrets within at least one of the first solution compartment and the second solution compartment, the plurality of electrets being sized and shaped to accumulate the charged molecules at a focal zone on the first solution compartment side of the valve.

[0010] In another implementation according to the first aspect, the device further includes a cavity in the valve for receiving a charged molecule, wherein rotation of the cavity relative to the barrier causes delivery of the charged molecule in the cavity from a first solution compartment side of the valve to a second solution compartment side of the valve.

[0011] Optionally, the valve is made of a conductive material and includes a conductive extension on a side opposite the cavity. A first electret and a second electret are configured on each portion of the barrier facing the second solution compartment. When the cavity faces the first solution compartment, the conductive extension is configured parallel to the first electret, thereby inducing a charge gradient in the valve that attracts charged molecules toward the cavity. After rotation of the valve so that the cavity faces the second solution compartment, the conductive extension is parallel to the second electret, thereby inducing a charge gradient in the valve that repels charged molecules from the cavity.

[0012] Optionally, the apparatus further includes a first barrier section made of an insulating material configured to separate the first electret and the bulb extension, and a second barrier section made of an insulating material configured to separate the second electret and the bulb extension.

[0013] In another implementation according to the first aspect, the valve has a plug movable relative to a barrier, the plug having a microchannel that allows fluid to pass through, and movement of the plug relative to the barrier toward the inside of the first solution compartment reduces the volume of the first solution compartment, thereby inducing the flow of charged molecules through the microchannel into the second solution compartment.

[0014] Optionally, the plug comprises an agglomerate of one or more of microbeads, microspheres, ceramic material, or powder material.

[0015] Optionally, the device further includes a spring configured on the second solution compartment side of the plug, an extension of the spring causing movement of the plug toward the inside of the first solution compartment.

[0016] Optionally, the device further includes a first magnet attached to the plug and a second magnet fixed to an opposite end of the first solution compartment relative to the plug, wherein magnetic attraction between the first magnet and the second magnet causes movement of the plug.

[0017] Optionally, a first electrostatic charge is applied to the plug and a second electrostatic charge is fixed at an opposite end of the first solution compartment relative to the plug, and an electrostatic force between the first and second charges causes movement of the plug.

[0018] Optionally, the plug is made of a conductive material.

[0019] Optionally, the plurality of electrets include an electret layer configured in the first solution compartment, the electret layer configured to: (1) repel charged molecules from the end of the first solution compartment toward the plug, (2) induce a dipole in the plug; and (3) exert an electrostatic force on the plug after inducing the dipole in the plug, thereby: attracting the plug toward the inside of the first solution compartment, reducing the volume of the first solution compartment, and inducing the flow of charged molecules through the microchannel to the second solution compartment.

[0020] Optionally, the induced dipole of the plug repels charged molecules in the second solution compartment from the plug.

[0021] In another implementation according to the first aspect, the valve includes a plug having a microchannel that allows fluid passage; the plug is made of a conductive material. The plurality of electrets includes an electret layer configured in the first solution compartment. The electret layer is configured to: (1) repel charged molecules from the end of the first solution compartment toward the plug, and (2) induce dipoles in the plug. The device further includes a sample holder consisting of a plurality of charged beads, the plurality of beads being bonded with a dissolvable adhesive. Upon introduction of the sample holder holding the sample into the first solution compartment: the solution in the first solution compartment dissolves the adhesive, thereby releasing the plurality of beads into the first solution compartment; and the electret induces the movement of the charged molecules into the plug, the diffusion of the charged molecules through the plug, and the movement of the released beads into the plug.

[0022] Optionally, the beads have an at least partially dissolvable surface and an adhesive configured within the surface, where dissolution of the surface releases the inner adhesive, thereby allowing the beads to bind in the plug and block passage of oppositely charged molecules through the plug.

[0023] In another implementation according to the first aspect, the first solution compartment contains one or more chemicals configured to degrade the biological sample into double-stranded or single-stranded DNA.

[0024] In another implementation according to the first aspect, the device further includes a sensor in the second solution compartment configured to test for the presence of a particular single-stranded strand of DNA.

[0025] According to a second aspect, a method of transferring charged molecules between a first solution compartment and a second solution compartment is disclosed, the method comprising: delivering the charged molecules to a focal zone of a valve configured in a barrier between the first solution compartment and the second solution compartment through the action of a plurality of electrets in at least one of the first solution compartment and the second solution compartment; and transferring the charged molecules through the valve.

[0026] In another implementation according to the second aspect, the valve has a cavity therein for receiving charged molecules, and the method further includes rotating the cavity relative to the barrier, thereby delivering the charged molecules in the cavity from a first solution compartment side of the valve to a second solution compartment side of the valve.

[0027] Optionally, the valve member is made of a conductive material and includes a conductive extension on a side opposite the cavity. A first electret and a second electret are configured on each portion of the barrier facing the second solution compartment. When the cavity faces the first solution compartment, the conductive extension is configured parallel to the first electret, thereby inducing a charge gradient in the valve that attracts charged molecules toward the cavity. After the rotation step, the valve extension is parallel to the second electret, thereby inducing a charge gradient in the valve that repels charged molecules from the cavity.

[0028] Optionally, the valve comprises a plug movable relative to the barrier, the plug having a microchannel that allows fluid passage, and the transferring step comprises moving the plug relative to the barrier toward the inside of the first solution compartment, thereby reducing the volume of the first solution compartment and inducing the flow of charged molecules through the microchannel into the second solution compartment.

[0029] Optionally, the method further comprises causing movement of the plug through an extension of the spring.

[0030] Optionally, the method further includes causing movement of the plug through magnetic attraction between a first magnet attached to the plug and a second magnet fixed to an opposite end of the first solution compartment relative to the plug.

[0031] Optionally, the method further includes causing movement of the plug through an electrostatic force induced between a first electrostatic charge applied to the plug and a second electrostatic charge fixed to an opposite end of the first solution compartment relative to the plug.

[0032] Optionally, the plug is made of a conductive material.

[0033] Optionally, the plurality of electrets include an electret layer configured in the first solution compartment, and the method further includes, through the action of the electret layer: repelling charged molecules from an end of the first solution compartment toward the plug, and inducing a dipole in the plug; and, after inducing the dipole in the plug, exerting an electrostatic force on the plug, thereby: attracting the plug toward the electret layer, reducing the volume of the first solution compartment, and inducing the flow of charged molecules through the microchannel to the second solution compartment.

[0034] In another implementation according to the second aspect, the valve includes a plug having a microchannel that allows fluid passage. The plug is made of a conductive material; and a plurality of electrets include an electret layer configured in the first solution compartment. The electret layer is configured to: (1) repel charged molecules from an end of the first solution compartment toward the plug, and (2) induce dipoles in the plug. The method further includes receiving a sample in the first solution compartment on a sample holder consisting of a plurality of charged beads, the beads being bonded with a dissolvable adhesive, dissolving the adhesive with a solution in the first solution compartment, thereby releasing the beads into the first solution compartment; and using the electret layer to induce movement of the charged molecules into the plug, diffusion of the charged molecules through the plug, and movement of the released beads back into the plug.

[0035] In another implementation according to the second aspect, the method further comprises degrading the biological material into double-stranded or single-stranded DNA in the first solution compartment.

[0036] In another implementation according to the second aspect, the method further comprises testing the sample in the second solution compartment for the presence of a particular single-stranded DNA strand. [Brief explanation of the drawings]

[0037] [Figure 1A] 1A-1H illustrate steps for isolating single-stranded DNA from a biological sample according to an embodiment of the present disclosure. [Figure 1B] 1A-1H illustrate steps for isolating single-stranded DNA from a biological sample according to an embodiment of the present disclosure. [Figure 1C] 1A-1H illustrate steps for isolating single-stranded DNA from a biological sample according to an embodiment of the present disclosure. [Figure 1D] 1A-1H illustrate steps for isolating single-stranded DNA from a biological sample according to an embodiment of the present disclosure. [Figure 1E] 1A-1H illustrate steps for isolating single-stranded DNA from a biological sample according to an embodiment of the present disclosure. [Figure 1F] 1A-1H illustrate steps for isolating single-stranded DNA from a biological sample according to an embodiment of the present disclosure. [Figure 1G] 1A-1H illustrate steps for isolating single-stranded DNA from a biological sample according to an embodiment of the present disclosure. [Figure 1H] 1A-1H illustrate steps for isolating single-stranded DNA from a biological sample according to an embodiment of the present disclosure. [Figure 2A] 2A-2B illustrate variations on the steps depicted in FIGS. 1A-1H, according to an embodiment of the present disclosure. [Figure 2B] 2A-2B illustrate variations on the steps depicted in FIGS. 1A-1H, according to an embodiment of the present disclosure. [Figure 3(a)-(b)] 3A-P illustrate an apparatus and method for transferring material from a biological sample between adjacent solution compartments of a "smart vial" according to an embodiment of the present disclosure. [Figure 3(c)-(d)] 3A-P illustrate an apparatus and method for transferring material from a biological sample between adjacent solution compartments of a "smart vial" according to an embodiment of the present disclosure. [Figure 3(e)-(g)] 3A-P illustrate an apparatus and method for transferring material from a biological sample between adjacent solution compartments of a "smart vial" according to an embodiment of the present disclosure. [Figure 3(h)-(j)] 3A-P illustrate an apparatus and method for transferring material from a biological sample between adjacent solution compartments of a "smart vial" according to an embodiment of the present disclosure. [Figure 3(k)-(m)] 3A-P illustrate an apparatus and method for transferring material from a biological sample between adjacent solution compartments of a "smart vial" according to an embodiment of the present disclosure. [Figure 3(n)-(p)]3A-P illustrate an apparatus and method for transferring material from a biological sample between adjacent solution compartments of a "smart vial" according to an embodiment of the present disclosure. [Figure 4] 4A-B illustrate the transfer of biomaterial between adjacent solution compartments using a rotating valve according to an embodiment of the present disclosure. [Figure 5(a)-(c)] 5A-F illustrate the transfer of biomaterial between adjacent solution compartments using a conductive valve where an electrostatic effect is induced by an electret, according to an embodiment of the present disclosure. [Figure 5(d)-(f)] 5A-F illustrate the transfer of biomaterial between adjacent solution compartments using a conductive valve where an electrostatic effect is induced by an electret, according to an embodiment of the present disclosure. [Figure 6(a)] 6A-C illustrate the transfer of biomaterials using a valve configured as a porous plug having a microchannel therethrough, according to an embodiment of the present disclosure. [Figure 6(b)] 6A-C illustrate the transfer of biomaterials using a valve configured as a porous plug having a microchannel therethrough, according to an embodiment of the present disclosure. [Figure 6(c)] 6A-C illustrate the transfer of biomaterials using a valve configured as a porous plug having a microchannel therethrough, according to an embodiment of the present disclosure. [Figure 7(a)] 7A-B illustrate a method for actuating the transport of charged material through the porous plug of FIGS. 6A-C according to an embodiment of the present disclosure. [Figure 7(b)] 7A-B illustrate a method for actuating the transport of charged material through the porous plug of FIGS. 6A-C according to an embodiment of the present disclosure. [Figure 8(a)] 8A-F illustrate the transport of biomaterial through a porous plug that is electrically conductive, according to an embodiment of the present disclosure. [Figure 8(b)] 8A-F illustrate the transport of biomaterial through a porous plug that is electrically conductive, according to an embodiment of the present disclosure. [Figure 8(c)]8A-F illustrate the transport of biomaterial through a porous plug that is electrically conductive, according to an embodiment of the present disclosure. [Figure 8(d)] 8A-F illustrate the transport of biomaterial through a porous plug that is electrically conductive, according to an embodiment of the present disclosure. [Figure 8(e)] 8A-F illustrate the transport of biomaterial through a porous plug that is electrically conductive, according to an embodiment of the present disclosure. [Figure 8(f)] 8A-F illustrate the transport of biomaterial through a porous plug that is electrically conductive, according to an embodiment of the present disclosure. [Figure 9(a)] 9A-E illustrate automated transfer of biomaterial through a plug using charged beads according to an embodiment of the present disclosure. [Figure 9(b)] 9A-E illustrate automated transfer of biomaterial through a plug using charged beads according to an embodiment of the present disclosure. [Figure 9(c)] 9A-E illustrate automated transfer of biomaterial through a plug using charged beads according to an embodiment of the present disclosure. [Figure 9(d)] 9A-E illustrate automated transfer of biomaterial through a plug using charged beads according to an embodiment of the present disclosure. [Figure 9(e)] 9A-E illustrate automated transfer of biomaterial through a plug using charged beads according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0038] Detailed Description of the Invention The present invention relates to the sensing of biomolecules and DNA-like molecules. In particular, the present invention relates to multi-chamber implementations of such sensor devices. More specifically, the present invention relates to an apparatus and method for transferring material from a biological sample between adjacent compartments, each compartment having a different solution for acting on the biological sample and isolating single-stranded DNA from the biological sample, allowing for examination of the isolated DNA strands.

[0039] Before describing at least one embodiment of the present invention in detail, it should be understood that the invention is not necessarily limited in its application to the details of construction and arrangement of components and / or methods set forth in the following description and / or illustrated in the drawings and / or examples. The invention is capable of other embodiments or of being practiced or carried out in various ways. In particular, throughout this disclosure, when the disclosure describes an element as "may" be present, it is understood that the described element is not necessarily present and that the element may be replaced by an equivalent element or may not be present at all. Similarly, when a list of particular examples is provided, the list is not necessarily exclusive, even in the absence of a disclaimer such as "including but not limited to," and other suitable examples may be utilized.

[0040] The sensor devices described herein are configured, in certain embodiments, for sensing DNA or DNA-like samples. While the analyte will be referred to as "DNA" throughout the remainder of this disclosure, the sensor devices described herein may also be used to sense other materials in general, and other types of DNA-like materials, such as RNA or fragments thereof, in particular. With appropriate modifications, the principles described herein are applicable to isolating any biological or non-biological material for sensing. In an advantageous embodiment, a DNA sample is collected from a body sample, such as a saliva or oral mucosa specimen. This vial may be used to detect specific DNA or DNA-like strands (e.g., RNA) from cells of an individual, a microbiome, or a virus. The DNA sample is then isolated within the sensor device through the action of a chemical solution and transported to a sensing element within the sensor device.

[0041] In certain embodiments, the sensors described herein are configured for sensing specific single-stranded DNA strands. The operating principles of these sensors are described in detail in the above-referenced applications, which are incorporated by reference as if fully set forth herein. In summary, each sensor contains one or more specific synthetic strands of single-stranded complementary DNA (sscDNA). When strands of ssDNA from a sample come into contact with the sensor's sscDNA, they hybridize with the sensor's sscDNA, creating double-stranded DNA (dsDNA). The sensor is configured to measure differences in physical properties resulting from the hybridization of the sscDNA. For example, the sensor's ssDNA may be configured between the plates of a capacitor that is part of a resonant circuit. Binding of the analyte ssDNA to the sensor's sscDNA causes a change in the capacitance of the capacitor, which in turn causes a change in the resonant frequency of the resonant circuit. The resonant circuit may act as a band-stop filter for the specific frequencies transmitted and received by the transceiver. In an alternative embodiment, the sensor's single-stranded DNA is configured between adjacent optical waveguides of an optical coupler, and binding of the analyte's ssDNA to the sensor's sscDNA changes the wavelength of light that can be coupled across the optical coupler. This sensor device and the system in which it resides further include means (e.g., a detector) that can monitor these physical changes.

[0042] To ensure that the sensor can effectively distinguish between solutions in which analyte DNA is absent and solutions in which analyte DNA is present but inaccessible to the DNA at the sensor, it is preferable to isolate the analyte DNA from other materials. This can be achieved by various techniques, such as gel electrophoresis. However, many such techniques require expensive laboratory equipment and trained technicians. The present disclosure introduces a low-cost device that can be operated by a layperson and is capable of isolating ssDNA from biological samples. The device contains various solutions for degrading a biological sample (e.g., saliva or oral mucosa specimen) into ssDNA and isolating the DNA strands from the remainder of the biological material. Specifically, the device includes different compartments, each containing a different solution for degrading the biological sample, and valves between each compartment.

[0043] The device further includes a means for attracting the analyte DNA to the valve region, preferentially transporting the analyte DNA from each compartment to the next, while leaving other materials from the biological sample behind. In many of the examples shown herein, these means are electrets. As used in this disclosure, an electret is a material with polarities incorporated, creating a positive charge on one surface and, if so designed, a negative charge on the opposite surface. Generally, electrets are prepared from polymer sheets by applying a high voltage to the polymer film while it is heated, causing the molecules to shift and thus creating a charge distribution. Because DNA molecules have an inherent negative charge, the positive pole of the electret attracts DNA molecules, while the negative pole of the electret repels them. Alternatively, a positively charged monopolar material may be used to attract negatively charged species and bring them into contact with molecules attached to the sensing zone.

[0044] 1A-H, the steps required to prepare a sample for sensing are generally disclosed. The procedure begins by collecting a sample from an individual into a container 101. The collected sample is transferred by some means, depicted in the figure by a pipette tip 100, into a vial 102a. The vial is preferably made of some polymer or any other material. The sample 103a may contain several liquid substances and several species, such as cells or other components, that may be present in a sample such as saliva or blood. In the next step, as shown in FIG. 1B, a dissociation substance 104a, such as protein kinase (PK), is contacted with the sample by, for example, pouring it into the vial. The dissociation substance PK disrupts the cell walls and nuclear walls (if present) of the biological material and releases DNA molecules 103b and / or RNA molecules. Once the DNA molecules are released, another substance 104b is poured into contact with the solution in the vial 102a. This solution contains a restriction enzyme (RE) 104b designed to cleave the DNA into fragments 103c according to predetermined criteria, as shown in FIG. 1C. At this point, optionally, according to FIG. 1D, the solution in vial 102a is filtered through a filtration porous medium 105a, ultimately leaving only the desired fragments 103c in solution. The filtered solution is delivered into a different vial 102b containing a dissociation solution 104c, such as NaOH, which dissociates the double-stranded DNA fragments into single-stranded DNA fragments 103d. It should be understood that filter 105 and the embodiment of the filter depicted in FIG. 2A may, but do not necessarily, appear as shown. Many forms of filters are available that may look different and be made from different materials and configurations, including looking like a disk or paper, or any other conceivable format.

[0045] FIG. 1E shows the sample after the fragments have been dissociated into ssDNA fragment 103d1 and its complementary ssDNA molecule 103d2, which are measured by the sensor. Again, optionally, the solution is filtered through porous medium 105b, allowing only ssDNA molecules of the relevant size to pass through while retaining other sizes or uncleaved dsDNA fragments. The filtered solution is transferred to a new vial 102c. At this point, an optional step is to retrieve silica or glass microbeads 106a coated with artificial ssDNA strands, which are copies of the ssDNA to be analyzed, such as strand 103d1. The beads may be of any suitable size, such as micron- or nanoscale sizes. The beads may be spherical, but may also be ellipsoidal, rectangular, pyramidal, or any other geometric configuration. Furthermore, the beads may be made from a variety of materials, including glass, polymers, ceramics, metals, or magnetic materials. It is even possible to use beads made from the compressed DNA material itself, for example, by compressing oligos to form aggregates or clusters of DNA material (which may also be considered beads). Generally, beads may be hollow, formed from several layers of various materials, or any other combination. When the beads are placed in solution, if they are competent, the sample ssDNA strands will tend to hybridize with complementary molecules 103d2. This reaction is partially hindered by the presence of a dissociation solution 104c, such as NaOH. However, near the surface of the glass beads, the density of the solution decreases due to a chemical reaction between silica and NaOH, thus allowing the complementary strand 103d2 to hybridize with the strand on its surface and form a new complex 103e. This will leave primarily the ssDNA 353d1 under test in solution.

[0046] Now, as shown in FIG. 1F, the solution is optionally filtered again using a suitable filter 105c to block all remaining ssDNA fragments while leaving the ssDNA fragments 103d1 of interest in solution. At this point, the solution is introduced into a vial or tube 102d, preferably made of glass or silica. In this tube, beads 106b are present. The beads 106b have ssDNA fragments 103d2 attached to their surface, which are ssDNA complementary to the ssDNA molecules 103d1 of interest. The strands in the beads and in the solution tend to hybridize and form double-stranded molecules. Because the solution may still contain a separating solution 104c, such as NaOH, which inhibits hybridization, some means are employed to increase the binding efficiency. These include the use of glass tubes 102d, which react with the solution and reduce its density, as described above. Further, optionally, the means includes adding a dilution substance 104d to increase and reduce the effect of diluting the separation substance, thus allowing the ssDNA to bind to new complexes 103f as shown in Figure 1G. Finally, according to Figure 1H, the tube with the solution can optionally be centrifuged 107 so that the beads with dsDNA 103f are concentrated to the bottom and can be transferred by some method 108 to the sensor.

[0047] The steps and procedures shown above are illustrative of steps and general materials, but it should be clear that the same goal can be achieved with any variation known to those skilled in the art. For example, vials and tubes were used in the above description; however, compartments and connections between solutions could be used. It is also possible to place the solutions in stacked wet papers, and the filtration element may also be realized as a porous paper or disc, or a smart wipe product. Exemplary implementations of such smart wipe products are described in detail in the above-referenced U.S. Provisional Patent Applications Nos. 63 / 428,087 and 63 / 435,258, as well as in co-pending International Patent Application No. PCT / IL2023 / 051147, filed November 8, 2023, entitled "Multilayer Planar Sensor for the Detection of Materials Containing Specific DNA or DNA-Like Strands," the contents of which are incorporated by reference as if fully set forth herein. Instead of moving a solution from one container to another, it is also possible that it is the sample that is moved from one compartment to another through a pumping effect or under external physical means such as an electret.

[0048] It should also be apparent that while filters are illustrated in specific locations in the previous figures, other arrangements of filters are possible. For example, as shown in Figure 2A, filter 205a is between sample 201 and solution 204a, filter 205b is between solutions 204a and 204b, filter 205c is between solutions 204b and 204c, and filter 205d is between solution 204c and sensor 200. It should also be apparent that more or fewer steps and solutions can be implemented as needed.

[0049] Also, while the different solutions are shown as being implemented one after the other in some order, it should be understood that this is not required. For example, referring to Figure 2B, solutions 204a, 204b, and 204c are all placed together in the same flask / tube / vial / compartment at the same time as the sample material, and cells 203a are added thereto. Thus, as soon as the required species appear in solution, all of the chemical reactions occur simultaneously, breaking down the cells (203b1) and releasing DNA molecules 203b2, which are then cut into fragments 203c and finally separated into single strands 203d in the same place before being processed in other steps.

[0050] While the procedure described in Figures 1A-H generally includes all the major steps that would be employed in a typical laboratory experiment, it should also be apparent that some steps may be performed in different environments. For example, the steps described in Figure 1F may be performed differently. In such an example, beads 106b are already positioned between the electrodes of the sensor, and ssDNA sample 103d1 is brought into contact with the beads by the action of the electret. And, of course, as previously mentioned, all steps may occur on paper and filters soaked in appropriate solutions.

[0051] In particular, the isolation procedure may be carried out using a multi-compartment device, an embodiment of which is described in relation to the following figures:

[0052] 3A-P show a schematic diagram of a multi-compartment device for receiving a biological sample to be analyzed, degrading the biological sample into single-stranded DNA, isolating the single-stranded DNA from the remainder of the biological sample, and detecting specific DNA strands. This device may be considered a "smart vial." The vial contains multiple compartments, each containing the chemical, electrical, and transport elements necessary for detecting a specific DNA strand.

[0053] 3A-P show the general structure of vial 300 and the degradation and transport of biomaterials through adjacent compartments of vial 300. Figures 3A-P respectively show a cross-sectional view (left) at the center of the top view of vial 300 and a plan view (right). While the compartments are shown schematically as having a rectangular box geometry, the structure of each compartment may be of any suitable geometric shape, such as cylindrical, hexagonal, or asymmetric.

[0054] Vial 300 includes multiple compartments. In the illustrated embodiment, three compartments are shown. The three compartments hold substances 305a, 305b, and 305c. These substances (also referred to herein as solutions) are configured to interact with a biological sample. In the example described herein, the substances are chemical solutions, but the substance could also be a gel. The gel may fill a portion or the entire volume of the solution compartment. The gel may transport certain molecules from one side of the gel to the other while blocking other molecules, or act as a selective medium to block liquid transfer or mixing.

[0055] Each compartment is separated by a barrier. In different embodiments, the barrier may be made of a conductive or non-conductive material. A valve 303 is configured within the opening in the barrier and separates the contents of each compartment and allows for controlled transfer of substances between the compartments. Each compartment may also contain one or more electret structures 302. The electret structures may be located at specific locations within each solution compartment, including particularly near the valves 303. Additionally, the electret structures may be located within a sensor 304.

[0056] At least one of the compartments has an opening 301b for the insertion of a sample to be tested. This opening is closed by a cap 301a. The opening is presented in a schematic manner and other configurations for the opening are possible.

[0057] Referring to FIG. 3B, a sample 306 (e.g., saliva) is placed in either cap 301a (as shown) or corresponding hole 301b. The cap is positioned to close the opening, as shown in FIG. 3C. This action brings the sample into contact with solution 305a in the first compartment. The sample spreads by diffusion, such as through shaking, or through other mixing means. Chemicals in solution 305a act on the sample, and the sample begins to dissociate, producing intermediate product 306a. In particular, DNA molecules 307a will be isolated within solution 305a, as shown in FIG. 3E. At least initially, these DNA molecules are double-stranded. These molecules, like all DNA molecules, have negatively charged sites.

[0058] Referring to FIG. 3E, an electret 302a is positioned at one end of the first solution compartment. The electret 302a is oriented with its negative pole facing the DNA molecules. The negative pole of the electret repels the negatively charged DNA molecules. Furthermore, as seen in plan view, the electret 302a is sized and shaped so that electrostatic forces repel negatively charged molecules in a specific direction. For example, the electret 302a may be semicircular (as shown), parabolic, or shaped in any other way that delivers negative charge to a focal zone. Here, the focal zone, or where the electret directs the negatively charged molecules, is the zone near the valve 303a, as shown in FIG. 3F. The valve 303a has a cavity for receiving the negatively charged material therein.

[0059] In the illustrated embodiment, the electrets are configured to repel charged molecules toward the focal zone, but other configurations can be implemented in which the electrets are positioned so that the positive side faces the molecules and attracts them into the focal zone rather than repelling them. Furthermore, it is possible to achieve the desired focusing effect by using a combination of electrets, some attracting and some repelling, and by placing electrets at various locations in each solution compartment, including the valve itself.

[0060] Eventually, as shown in FIG. 3G, most of the negatively charged molecules will collect in the focal zone. Optionally, the solution in the compartment includes an indicator so that a color change 305a1 occurs when this occurs, thus indicating the completion of this process. At this point, valve 303a is actuated, for example, through one of the processes described below for specific valve configurations. In the illustrated embodiment, valve 303a is actuated through rotation, as shown in FIG. 3H. Rotation of valve 303a relative to the barrier causes delivery of the charged molecules within the cavity from the first solution compartment side of the valve to the second compartment side of the valve. As a result, the contents of the valve (primarily the negatively charged DNA fragments 307a collected therein) are blocked from the first compartment solution 305a and exposed to the second compartment solution 305b. Although this transfer method is not completely selective, as some material that is not a negatively charged DNA fragment may also be transferred into the second solution compartment, it is selective enough to enhance the concentration of DNA fragments and prevent most of the unrelated material that is not a DNA fragment from the biological sample from being transferred into the second solution compartment. The resulting difference in concentration of DNA fragments significantly improves the sensitivity of the sensor, especially when this process is repeated more than once. Additional specific embodiments of valves that may be even more selective are described further herein.

[0061] In the second solution compartment, fragments 307a begin to spread due to diffusion or through any other mixing process, as described above. Furthermore, electret 302b, which is similar in size and shape to electret 302a, begins to act on fragments 307a. The charged molecules eventually migrate toward and become concentrated in a focal zone near valve 303b (see FIG. 3I), as shown in FIG. 3I. Furthermore, as the charged molecules move within the second solution compartment, they are exposed to solution 305b, which contains chemicals that further act on the charged particles, converting fragments 307a into molecules 307b. Molecules 307b may be, for example, double-stranded or single-stranded DNA fragments. Because these molecules remain negatively charged, they migrate in a predetermined direction and accumulate in the focal zone near valve 303b, as shown in FIG. 3K. Optionally, indicator solution 305b can be prepared such that when molecules accumulate in the focal zone, a color change 305b1 occurs, as shown in FIG. 3L.

[0062] Valve 303b rotates as shown in FIG. 3M. This blocks material 307b from solution 305b in the second solution compartment and exposes material 307b to solution 305c in the third solution compartment. In the illustrated embodiment, the third is the final solution compartment, but it is clear that additional or fewer solution compartments may be implemented. Material 307b begins to diffuse or spread within the third solution compartment. In particular, material 307b may move due to electrostatic forces caused by electret 302c or other electrets, such as the electret in the sensor, as shown in FIG. 3N. Electret 302c has its negative pole facing the solution and repels negatively charged molecules toward the focal zone. As previously mentioned, the electret configuration may also have a positive pole facing the solution or any other configuration that would move molecules toward the sensor. During this movement, due to the action of a chemical in solution 305c, molecule 307b is converted into molecule 307c, as shown in FIG. 3O. Molecule 307c is the material desired to be tested, which in the example described herein is single-stranded DNA. Sensor 304 is present in the third solution compartment, as shown in FIG. 3P. Sensor 304 has electret material 302d with its positive side facing the solution, thus attracting negatively charged molecules and forcing them to pass through the sensing region (e.g., the gap between the two plates of a capacitor). As material 307c passes through the sensing region, if a strand of single-stranded DNA matches a corresponding strand of single-stranded DNA configured in the sensor, it will bind to the single-stranded DNA in the sensor. Other negatively charged molecules will pass through the sensing region and continue toward electret 302d. As previously explained, it is possible to add some chemical to solution 305c that will change color to 305c1 when the process is complete. The sensor device transmits a reading that indicates the presence of the analyte DNA strand, thus completing the sensing process.

[0063] 4A-B depict a first specific embodiment of a valve disposed between adjacent solution compartments of sensing device 400. FIG. 4A shows a portion of first solution compartment 401 and a portion of second solution compartment 402. A barrier 406 separates the solution compartments. Barrier 406 may be made of a variety of materials, including the material of the vial itself, and may optionally be integrally formed with the exterior of the vial. In this embodiment, barrier 406 is made of a non-conductive material. Electret 403 is configured adjacent to separation wall 406. The negative side of electret 403 faces second solution compartment 402. The opening between the first and second solution compartments is closed by valve 405a. Valve 405a is shown as having a hemispherical shape. As shown in FIG. 4A, valve 405a has a convex side facing second solution compartment 402 and a concave side facing first solution compartment 401. As described above, a sample placed in first solution compartment 401 will undergo a chemical reaction that will ultimately produce negatively charged molecules. Due to the action of the electret on the negatively charged species, the charged molecules will over time collect into a focal zone in the region of the valve. As described in connection with FIGS. 3A-P, this process may be implemented, at least in part, through the action of an electret (not shown) of a particular size and shape on the opposite side of first solution compartment 401.

[0064] Following the accumulation of negatively charged material in the cavity of valve 405a, the cavity rotates relative to barrier 406. The concave side of the valve "skims" or blocks solution 404 from first solution compartment 401 and releases or exposes it in second solution compartment 402. As shown in FIG. 4B, after this movement, the concave side of valve 405b points toward second solution compartment 402, while the convex side now faces first solution compartment 401, effectively blocking or closing off the first solution compartment from the second solution compartment. Rotation of the cavity may proceed through any suitable mechanism. For example, mechanical methods such as an external knob connected to a lever that is physically moved to change the position of the valve can be used. Electric, magnetic, or other motors connected to the valve, magnetic or electrostatic forces imposed on the valve, or pneumatic, hydraulic, or thermal mechanisms are also possible.

[0065] Once the charged material has been transferred into the second solution compartment 402, as described above, an electret 403 may be used to direct the charged particles toward the opposite end of the second solution compartment 402. In particular, the electret 403 has a positive pole facing the first solution compartment 401 (left side in the views of FIGS. 4A-B) and a negative pole facing the second solution compartment 402 (right side in FIGS. 4A-B). As a result, the electret 403 attracts negatively charged particles in the first solution compartment 401 toward the valve area and repels negatively charged particles in the second solution compartment 402 away from the valve.

[0066] It is also important to emphasize that while chemical solutions are referenced in the description, gels may also be used in the same places where solutions are mentioned. The gel may be placed in the first compartment, the second compartment, or even the valve area. The gel may fill the entire volume of the compartment or valve, or may extend into a portion of the volume. The gel may have several purposes, such as, but not limited to, use as a selective medium to transport some molecules from one side of the gel to the other while blocking other molecules, or to block fluids from transferring and mixing between compartments or valves, or other uses that are characteristic of gels.

[0067] 5A-F show another embodiment of the valve. Referring to FIG. 5A, a barrier 506 separates a first solution compartment 501 and a second solution compartment 502. The barrier 506 is preferably made of a non-conductive material, but may be conductive. The barrier 506 may be part of the vial's structure and may be made of the same or a different material. An electret 503 is disposed on the surface of the barrier 506. A portion of the electret is located near the opening between the solution compartments 501 and 502, where the valve 505a is located. The negatively charged side of the electret faces the second solution compartment 502, and the positively charged side of the electret faces the first solution compartment 502.

[0068] 5A-F, the bulb 505a is made of a conductive material. When the barrier 506 is non-conductive, the barrier 506 separates the electret 503 from the bulb 505a, preventing the charged surface of the electret from being directly connected to a conductor. However, this is not strictly necessary, and in other embodiments, it may be preferable to connect the electret to the conductive material of the bulb 505a.

[0069] Valve 505a is similar in many respects to the valves of FIGS. 4A-B and 3A-P. One important difference between valve 505a and the preceding embodiments, besides being made of a conductive material, is that valve 505a includes a conductive extension 507. Conductive extension 507 serves as a stop element to prevent the valve from rotating beyond a predetermined angle. Thus, when the concave side is open toward first solution compartment 501, extension 507 is blocked by the first section of barrier 506 and first electret 503, as shown in FIG. 5A. When the valve is rotated so that the concave side faces second solution compartment 502, as shown in FIG. 5F, extension 507 is blocked by the second section of barrier 506 and second electret 503.

[0070] The conductive extension 507 serves an additional purpose in addition to functioning as a blocking element to ensure proper valve orientation. Referring to FIG. 5B, a portion of the barrier 506 and adjacent structures is enlarged. In this view, it is clear that the first and second electrets consist of a positive side 503a and a negative side 503b, with the negative side facing the second solution compartment 502. The negative side is also partially surrounded by the first and second barrier sections 506 and 506. The barrier sections 506 are made of an insulating material and are configured to separate the first and second electrets from the conductive valve extension 507. The conductive extension 507 of the valve 505a is in intimate contact with the barrier 506. Due to electrostatic effects, the negative side 503b of the first electret induces a positive charge on the conductive extension 507 of the valve 505a. This induced charge is shown in Figure 5C. Furthermore, the movement of positive charge 508a toward the negative side 503b of the electret will also allow a negative charge 508b to form at the opposite end of bulb 505a. In other words, there will be areas of bulb 505a closer to the extension that are positively charged, and there will be areas of bulb 505a at a distance from the extension that are negatively charged.

[0071] As shown in Figure 5D, the charge induced in the region of the conductive bulb near extension 507 creates a distribution of charge within the bulb, with primarily positive charge facing the concave side of the bulb and a majority of negative charge facing the convex side of the bulb. This results in an increased positive charge on the concave side of the bulb facing the first solution compartment 501. Negatively charged material 504 in the first solution compartment is attracted to the increased positive charge in the bulb, as indicated by the arrows. Thus, the distribution of charge in the bulb complements the action of the electret, which concentrates negatively charged material 504 toward the bulb region.

[0072] 5F, the concave side now faces the second solution compartment 502. The valve blocks the first solution compartment 501 from contacting the charged material 504 or the second solution compartment 502. The extension 507 moves to a new position in the second solution compartment relative to the opening and makes contact with the second barrier section 506 and the electret material 503 underneath. The second barrier section 506 ensures the correct angle or position of the concave opening of the valve toward the second solution compartment 502.

[0073] Furthermore, due to the electrostatic effect of the negative side 503b of the second electret, the positive charge 508a on the conductive bulb and extension 507 at position 505b will be relocated near the negative electret charge. The negative charge 508b will be relocated toward the other side of the bulb 505b, as shown in Figure 5E. While Figures 5C and 5E appear similar at first glance, the end effect is different due to the different positions of the bulb extension and the concave side of the bulb relative to the electret. The positive charge attracted to the second electret is now near the convex side of the bulb. A negative induced charge 508b is induced on the concave side of the bulb, whereas a positive charge was generated at the previous valve position 505a. Thus, while in the previous valve position the induced charge of the valve attracted negative species 504, in the new configuration of valve 505b the negative charge repels negative species 504 as shown by the arrows, expelling the negative molecules into the second solution compartment 502.

[0074] In summary, when the cavity faces the first solution compartment, the conductive extension 507 is configured parallel to the first electret, thereby inducing a charge gradient in the valve 505 that attracts charged molecules into the cavity; and after rotation of the valve 505 so that the cavity faces the second solution compartment, the conductive extension is parallel to the second electret, thereby inducing a charge gradient in the valve that repels charged molecules from the cavity.

[0075] Many variations are possible for the conductive bulb 505 and extension 507 described herein. These variations include, but are not limited to, the bulb's size, geometry, and material; and the extension 507's geometry, placement, thickness, and other technical parameters. These components may be arranged so that electrostatically induced charges fill more or less of the bulb's area on either the concave or convex side. Furthermore, some zones of electret material may be made positive and some negative, as desired to influence the bulb's conductive material. Furthermore, the material of the barrier section 506 may be thicker or thinner at various points and have various geometries, as needed.

[0076] 6A-C show another embodiment of a valve. In contrast to the previous embodiment, in which the valve is fixed in position between the first and second solution compartments, in this embodiment the valve is movable. FIG. 6A schematically shows a valve between compartments of a device 600. A first solution compartment 601 and a second solution compartment 602 are separated by a barrier 606. In this embodiment, the barrier 606 is made of an insulating material that is non-conductive. On the side of the barrier 606 facing the second solution compartment 602 is an electret 603. The barrier 606 and the electret 603 have openings. While the figures show the extents of the openings in the separation element 606 and the electret 603 as if they were similar, this need not be the case, and one opening may have a larger or smaller dimension than the other.

[0077] A plug 605 is configured within the opening. In FIG. 6A, the plug is designated by reference numeral 605a. The plug 605 may be made of microbeads or microspheres packed together as an aggregate, either conductive or non-conductive, ceramic, gel, membrane, or any other porous material through which fluids or other substances may permeate, diffuse, flow, or pass from one side to the other. In an exemplary embodiment, the plug 605 is made of microbeads, which may be spherical or cubic, for example, and may be the same size or different sizes. The plug may also be made of powders pressed together. The plug 605 has microchannels that allow the passage of fluids under certain conditions, for example, when appropriate pressure is applied to one side of the plug. As will be explained below, the plug 605 acts as a valve.

[0078] The side of plug 605a facing first solution compartment 601 has an area 604 where negatively charged material has accumulated through the action of one or more electrets (not shown). This material is to be transferred to second solution compartment 602. As plug 605b moves, liquid 604b flows through a channel in the valve, leaving liquid 604a in first solution compartment 601. Liquid 604c accumulates on the other side of plug 605. Eventually, all of material 604a has been transferred through plug 605 and is accumulated on the second solution compartment side of plug 605. This completes the operation of the valve, effectively blocking the solution in first compartment 601 from the solution in second compartment 602 while allowing controlled transfer of material from side to side. The channels of plug 605 do not allow for an airtight seal, but in fact liquid can change position either by diffusion, which is a relatively slow process, or through the application of a pressure difference that only operates in a single direction.

[0079] When negatively charged material accumulates in zone 604, a force is applied to the plug, as shown in FIG. 6B. Specific manners in which this force may be applied will be described further herein. This force induces movement of plug 605 against the barrier toward the first solution compartment, as indicated by arrow 607. The plug moves away from second solution compartment 602 and into first solution compartment 601, reducing the volume of the first solution compartment 601. Because the liquid in the compartments is incompressible (except for slight compression due to gas that may be trapped in the solution), the advancement of plug 605 is only possible if the liquid correspondingly flows out of first solution compartment 602 and through a channel in plug 605. In an exemplary embodiment, the fluid used to pass the plug may be a superconducting fluid, such as liquid helium below its critical temperature. In such cases, due to the quantum nature of supercritical fluids, the fluid may pass through special glass materials even without a physical channel.

[0080] In the illustrated embodiment, plug 605 moves relative to wall 606, which remains stationary, but this movement is properly understood as relative movement. Thus, plug 605 may be stationary relative to barrier 606 or even relative to the overall structure of the vial, and these components may move relative to the plug to achieve the same relative movement. Furthermore, in alternative embodiments, the plug may not move at all; instead, a pressure drop in the second solution compartment or a pressure increase in the first solution compartment may induce flow through the channel in the plug. Furthermore, while it has been specified that flow occurs from the first solution compartment into the second solution compartment, this need not be the case, and solutions may be reversed as needed, even starting to flow in one direction and then continuing to flow in the opposite direction.

[0081] 7A-B illustrate various exemplary methods for directing the movement of a plug relative to a barrier 606. FIG. 7A illustrates an apparatus 700 similar to that of FIGS. 6A-B. The apparatus includes a first solution compartment 701 and a second solution compartment 702 separated by a barrier 706. An electret material 703 is configured on the side of the barrier 706 facing the second solution compartment 702. A plug 705 is configured within an opening in the barrier 706. Within the first solution compartment 701, a region 704 is a "focal zone" where negatively charged material accumulates for transport to the other side of the plug 705 relative to the second solution compartment 702. These elements are similar to the equivalent elements described in connection with FIGS. 6A-C, and for the sake of brevity, a detailed description of those elements will not be repeated here.

[0082] Referring to FIG. 7A , spring 708a is used to induce relative motion of plug 705, as indicated by arrow 707. The extension of spring 708a causes spring 708 to push against plug 705. As spring 708a pushes against the plug, solution begins to flow through the channel in the plug, thereby reducing the solution pressure in the first solution compartment and allowing spring 708a to continue forward. The speed of plug 705 movement depends, among other things, on the spring constant, the resistance to movement posed by the incompressible fluid, and the ability of the fluid to pass through the microchannel of plug 705 conversely. The lower the resistance to flow through plug 705 and the higher the spring force, the faster plug 705 will advance. The timing of plug 705 movement may be appropriately set to allow analyte species to accumulate in region 704 and pass to the other side of plug 705, as desired.

[0083] The spring 708a may be of any suitable geometry or type to achieve the effects described herein. In the illustrated embodiment, the spring 708a is a coil spring. Alternatively, the spring may be a cantilever spring or may be an elastic material such as rubber. The spring may be a shape memory alloy (SMA), whose shape may be changed (e.g., expanded) by, for example, applying a heating sequence or using any other suitable method.

[0084] FIG. 7B illustrates another embodiment of a method for actuating plug 705. In this embodiment, plug 705 is attached to a first magnet 709a, which may be of any relevant shape and size. The first magnet 709a may have its north pole oriented in any desired direction. In the illustrated example, the north pole generally faces the second solution compartment 702. A second magnet 709b, which may be inside or outside the first solution compartment, will influence the first magnet 709a. With the second magnet 709b pointing its north pole toward plug 705, it creates an attractive force with the south pole of the first magnet 709a and pulls plug 705, causing it to begin moving in direction 707. Again, the speed of movement depends on the flow resistance posed by the channel in the plug and the force exerted between the magnets. Obviously, the same result would be achieved if the south pole of each magnet were pointing to the right instead of the left in Figure 70B. Furthermore, a second magnet 709b could be placed in the second solution compartment 702 with its north pole pointing toward the north pole of the first magnet 709a. Thus, the poles would repel each other, and the plug would be pushed away from the magnet instead of being attracted to it. In another alternative, one or both of the first magnet 709a and the second magnet 709b could be electromagnets. Advantageously, this type of magnet would allow for more controllable movement, although it would require a current source to energize the magnet's coils.

[0085] Instead of magnets, electrostatic dipoles and / or charges can be used, such that magnet 709b may be replaced with a dipole element such as an electret. For example, the north pole may be replaced by a positive electrostatic charge and the south pole by a negative electrostatic charge. Electrostatic charges attract or repel each other using electrostatic forces. Each charge element may have a single charge rather than the dipoles required for magnets. Thus, instead of electrets, which are electrostatic dipoles, elements 709a and 709b may have opposite electrostatic charges if an attractive force is desired, or electrostatic charges of the same sign (both positive or negative) if a repulsive force is desired. Any combination of the methods described herein may be utilized, including spring, magnetic, and electrostatic attractive or repulsive forces.

[0086] 8A-F illustrate another embodiment of a plug, specifically made of a conductive material, and a method for actuating the movement of the conductive plug. Except for being made of a conductive material, the plug may be of similar structure to the previously described plug embodiments.

[0087] 8A-F depict close-ups of sensing device 800. The close-ups are of the valve region. First and second solution compartments 801 and 802 are separated by a barrier 806. An electret layer 803a may be disposed on top of the barrier 806. The electret 803a is positioned in such a way that it does not interfere with the flow of fluid through the valve and, in fact, plays no role in the transfer of fluid between the first and second solution compartments. The barrier 806 has an opening in which a plug 805a is disposed. The geometries of the openings on the separation structure 806 and the electret 803a can be, but need not be, equal. Specifically, the opening in the barrier 806 may be smaller than, equal to, or larger than the opening in the electret. In the illustrated embodiment, the electret layer 803a is positioned on the side of the barrier pointing towards the second solution compartment 802, with its negative side facing the solution, to repel negatively charged substances entering the second solution compartment 802. In the illustrated embodiment, the opening in the electret layer 803a is larger than the opening in the separation structure 806. The electret layer 803a is depicted in this manner to emphasize that electrostatic effects due to the electret 803a do not occur in the region of the valve and that the electret 803a only has an effect on substances already in the second solution compartment. Those skilled in the art will be familiar with other possible positions and sizes of the electret.

[0088] 8A shows an electret layer 803b in the first solution compartment 801. While this electret layer is shown schematically as linear, it may be oriented in a curved manner and, as previously described, as part of a larger electret configuration to concentrate charged materials in a focal zone in the region of the valve. In the illustrated example, the negative side of the electret layer 803b points toward the first solution compartment 801 and the barrier 806. The first solution compartment 801 contains charged materials 804a and includes therein molecules of particular interest 804b. The negatively charged molecules are repelled by the electrostatic effect of the electret 803b and migrate in direction 807 toward the opening in the separation structure 806 where the plug 805a resides.

[0089] 8B, because plug 805a is conductive, electret layer 803b, in addition to its effect on the charged particles in first solution compartment 801, also induces a redistribution of charge on plug 805a. The side of plug 805a closer to the negative side of electret 803b will be charged with a positive charge 805a1. As a result, the other side of conductive plug 805a facing second solution compartment 802 will be charged with a negative charge 805a2.

[0090] Referring to FIG. 8C, negatively charged species 804a1 and 804b1 continue to move in direction 807b and accumulate in a zone near the positive side of the plug. These species are both repelled by electret 803b and are also attracted by the induced charge 805a1 of conductive plug 805a. Because species such as particles and molecules are small and mobile relative to the plug in solution, the movement of the species occurs more quickly than the movement of the plug. Thus, eventually, as shown in FIG. 8D, a significant amount of negative material 804a2 and the molecules 804b2 therein will accumulate and form zone 804c containing the material to be transferred to the second solution compartment.

[0091] As previously mentioned, due to electret 803b, charge redistribution occurs in plug 805a, along with the effect on material 804, and electret 803b exerts a force on plug charge 805a1. This force initially separates the positive charge of plug 805 on one side and the negative charge on the other side. This force then acts to attract plug 805 and induce its movement in direction 807c, as shown in Figure 8E. In theory, a force inducing plug movement exists even before the accumulation of molecules in zone 804c, but in practice, plug movement becomes significant after the accumulation of molecules. This is due to various physical factors, including, for example, frictional forces on the plug and drag caused by fluid flowing through the microchannel on the plug. As a result of the plug's movement, material 804c1 accumulated near the plug will transport through the microchannel within the plug and accumulate on the other side of the plug as material 804c2. Negatively charged molecules 804b3 will appear on the side of the plug that has an induced negative charge 805a2. Movement of the plug forces the accumulated material 804c1 to migrate from side to side, and by doing so induces a negative charge that may have been slightly attracted by the induced positive charge in the portion of the plug facing the first solution compartment, overcoming the charge-based attractive force and moving to the other side of the plug 805.

[0092] Eventually, as shown in FIG. 8F, material will have passed from the first solution compartment side of the plug to the second solution compartment side of the plug and accumulated in region 804c3. Plug 805c completes its function as a valve while moving in direction 807d. Charged material on the other side of the plug is exposed to negative charges 805a2 caused by the induced dipole. These charges repel the transferred negative species (optionally in combination with electret 803a). Therefore, those negative species move in direction 807e toward the interior of second solution compartment 802.

[0093] 9A-E show another embodiment of a valve with a plug. Device 360 ​​has many features similar to the previous embodiment. For brevity, they will be briefly mentioned here. First solution compartment 901 and second solution compartment 902 are separated by barrier 906. For purposes of this illustration, barrier 906 is described as being of a non-conductive or insulating material. Electret material 903a is on the side of barrier 906 facing second solution compartment 902. Electret layer 903b is configured within first solution compartment 901 and may be shaped to direct charged material toward a focal zone, as previously described. Electret layer 903b has its negatively charged side toward the first solution compartment and the valve, directing the movement of negatively charged material toward the valve.

[0094] A plug 905 is configured in a hole in the barrier 906 and functions as a valve connecting the first and second solution compartments. In the illustrated embodiment, unlike previous embodiments involving a plug, the plug 905 is stationary relative to the barrier 906 and may in principle be fixed to the barrier 906.

[0095] Referring to FIG. 9A, a sample is introduced into the solution. As previously mentioned, the sample may be introduced in a variety of ways, including directly into an opening on a vial or through a placement in a cap that seals the opening of the vial. In the illustrated embodiment, the sample is placed in a sample holder that is inserted into the solution. The sample holder consists of a substrate 908 and a layer of beads 909. The beads 909 may be of any suitable shape, such as spherical, pyramidal, or block-like. The beads 909 may be solid or hollow and may be made of multiple layers. The beads are secured in place by the use of a dissolvable adhesive. The sample 904a is placed on the beads 909. A separate substrate layer 908 is not necessary if the beads are bonded to form a substantially rigid surface, similar to a substrate, that can hold the sample.

[0096] The beads 909 are made of a material that has at least a partial charge. In the embodiment shown, the charge on the beads is negative, as is the charge on the species to be moved in solution.

[0097] Referring to Figure 9B, once the sample holder with the sample is introduced into the solution, chemical reactions begin to occur as described above in connection with Figures 3A-P. These reactions dissolve the sample and separate it into substances 904b, specifically negatively charged substances 904c, among which potentially reside molecules or species of particular interest 904d. The electret layer induces the migration of charged molecules toward the plug. Due to the effect of the negatively charged side of electret 39B, and potentially due to negatively charged beads 909, all negatively charged species will begin to migrate in direction 907a toward plug 905.

[0098] At the same time, the adhesive that binds the beads 909 to each other and to the optional substrate begins to dissolve or loosen due to the effect of the solution on the agent binding the beads. The beads are released into solution 909a. Electret layer 903b causes the released beads 909 to move into the plug. All negatively charged elements (including beads 909a, negative species released into solution from sample 904c1, including a portion of sample of interest 904d1) move in direction 907b toward plug 905. Negative species 904c1, 904d1 are released more quickly and are typically smaller and more agile than beads 909a; therefore, they will reach plug 905 sooner than the larger and relatively slower beads 909a.

[0099] Referring to FIG. 9D, when species arrive at the plug, they accumulate on side 904c2. Due to electrostatic repulsion caused by the electret layer and accumulated charged beads 909B, the charged molecules will diffuse through channel 904e in plug 905 to the other side of the plug. Unlike the embodiments of FIGS. 6A-6C, 7A-7B, and 8A-8F, fluid remains on the first solution compartment side of plug 905, and only species pass through plug 905. Electrostatic forces cause migration only for species. Species accumulate in zone 904f, including species of interest 904d2, if present. Simultaneously, the remainder of the charged species continue their movement 907b toward plug 905, including beads 909b, which begin to accumulate near plug 905.

[0100] Referring to FIG. 9E, eventually, most of the negatively charged species are transported through the plug and accumulate in region 904f1 on the second solution compartment 902 side of the plug. Beads 909c, which are larger than the passageways of the plug 905, cannot pass through the plug 905 and therefore accumulate on the first solution compartment 901 side of the plug 905, effectively blocking further passage of generally negatively charged (due to repulsion effects) and other species. The beads become aligned along the surface of the plug due to the combined electrostatic effects of the electret layer and the induced dipoles of the plug. The design of the charges on the electret, the size of the beads, and the distribution of channels in the plug define the optimal flow of seeds on the one hand and the effective blocking of unintended species through the plug on the other hand. In addition to electret 903b, the negatively charged field of the beads forms a wall 909c that further repels negative species that accumulate in region 904f1, thus causing negatively charged species 904c3, and in particular certain species 904d3, to move in direction 907c towards the second solution compartment 902.

[0101] Optionally, beads 909 are hollow. Hollow beads store material. The surface of the beads may be made at least in part of a dissolvable material. When the beads are released into solution, the walls begin to collapse, and as the released beads accumulate on the surface of plug 905 and form walls 909c that block passage within plug 905, openings occur on the surface of the beads, thus allowing material to be released from the beads' interior. This released material flows out of the beads and creates a membrane or other structure that binds the beads. The bound beads block the reverse passage of charged particles through the plug. The dissolvable material on the surface of the beads may be selected and applied in an appropriate thickness, for example, so that the dissolution fully opens the opening only after beads accumulate on the surface of plug 905. Furthermore, it will be appreciated by those skilled in the art that the plug structure and the microchannels and passages therein can be configured to filter species passing through them according to size, such that only molecules or particles of a predetermined size can pass from one compartment to another, thus improving the selectivity of this type of plug.

Claims

1. 1. A device for transferring charged molecules between a first solution compartment and a second solution compartment, the device comprising: a barrier disposed between the first solution compartment and the second solution compartment; a valve configured within the barrier; and a plurality of electrets in at least one of the first solution compartment and the second solution compartment, the plurality of electrets being sized and shaped to cause the charged molecules to accumulate at a focal zone on the first solution compartment side of the valve; The device.

2. 2. The device of claim 1, further comprising a cavity within the valve for receiving the charged molecule, wherein rotation of the cavity relative to the barrier causes delivery of the charged molecule within the cavity from the first solution compartment side of the valve to a second solution compartment side of the valve.

3. 3. The device of claim 2, wherein the valve is made of a conductive material and includes a conductive extension opposite the cavity, and a first electret and a second electret are configured on each portion of the barrier facing the second solution compartment, and when the cavity faces the first solution compartment, the conductive extension is configured parallel to the first electret, thereby inducing a charge gradient in the valve that attracts the charged molecules toward the cavity; and after rotation of the valve so that the cavity faces the second solution compartment, the conductive extension is parallel to the second electret, thereby inducing a charge gradient in the valve that repels the charged molecules from the cavity.

4. 4. The device of claim 3, further comprising a first barrier section made of insulating material configured to separate the first electret and the bulb extension, and a second barrier section made of insulating material configured to separate the second electret and the bulb extension.

5. 2. The device of claim 1, wherein the valve comprises a plug movable relative to the barrier, the plug having a microchannel that allows fluid passage, and movement of the plug relative to the barrier toward the inside of the first solution compartment reduces the volume of the first solution compartment, thereby inducing a flow of the charged molecules through the microchannel into the second solution compartment.

6. The device of claim 5 , wherein the plug comprises an aggregate of one or more of microbeads, microspheres, ceramic material, or powder material.

7. 6. The device of claim 5, further comprising a spring configured on the second solution compartment side of the plug, wherein expansion of the spring causes the movement of the plug toward the interior of the first solution compartment.

8. 6. The device of claim 5, further comprising a first magnet attached to the plug and a second magnet fixed to an opposite end of the first compartment relative to the plug, wherein magnetic attraction between the first magnet and the second magnet causes movement of the plug.

9. 6. The device of claim 5, further comprising a first electrostatic charge attached to the plug and a second electrostatic charge fixed to an opposite end of the first compartment relative to the plug, wherein an electrostatic force between the first and second charges causes movement of the plug.

10. 6. The device of claim 5, wherein the plug is made of a conductive material.

11. 11. The device of claim 10, wherein the plurality of electrets comprises an electret layer configured in the first solution compartment, the electret layer configured to: (1) repel the charged molecules from the end of the first solution compartment toward the plug; (2) induce a dipole within the plug; and (3) exert an electrostatic force on the plug after inducing the dipole within the plug, thereby: attracting the plug toward the interior of the first solution compartment, reducing the volume of the first solution compartment, and inducing a flow of the charged molecules through the microchannel to the second solution compartment.

12. 12. The device of claim 11, wherein the induced dipole in the plug repels the charged molecules in the second solution compartment from the plug.

13. the valve having a plug with a microchannel that allows fluid to pass through; the plug is made of a conductive material; the plurality of electrets having an electret layer configured in the first solution compartment, the electret layer configured to: (1) repel the charged molecules from the end of the first solution compartment toward the plug, and (2) induce a dipole within the plug; the device further comprising a sample holder comprising a plurality of charged beads, the plurality of beads being bonded together with a dissolvable adhesive; Upon introduction of the sample holder holding the sample into the first solution compartment: the solution in the first solution compartment dissolves the adhesive, thereby releasing the plurality of beads into the first solution compartment; and the electret induces the movement of the charged molecules into the plug, the diffusion of the charged molecules through the plug, and the movement of the released beads into the plug; 10. The apparatus of claim 1.

14. 14. The device of claim 13, wherein the beads have an at least partially dissolvable surface and an adhesive configured within the surface, and dissolution of the surface releases the inner adhesive, thereby allowing the beads to bind in the plug and block passage of the charged molecule in the opposite direction through the plug.

15. 10. The device of claim 1, wherein the first solution compartment contains one or more chemicals configured to degrade a biological sample into double-stranded or single-stranded DNA.

16. 10. The device of claim 1, further comprising a sensor configured to test for the presence of a specific strand of single-stranded DNA in the second solution compartment.

17. 1. A method for transferring a charged molecule between a first solution compartment and a second solution compartment, the method comprising: delivering the charged molecules to a focal zone of a valve configured in a barrier between the first solution compartment and the second solution compartment through the action of a plurality of electrets in at least one of the first solution compartment and the second solution compartment; and transferring the charged molecule through the valve. The method.

18. 18. The method of claim 17, wherein the valve includes a cavity therein for receiving the charged molecule, and the method further comprises rotating the cavity relative to the barrier, thereby delivering the charged molecule in the cavity from a first solution compartment side of the valve to a second solution compartment side of the valve.

19. 19. The method of claim 18, wherein the valve member is made of a conductive material and includes a conductive extension opposite the cavity, and a first electret and a second electret are configured on each portion of the barrier facing the second solution compartment, and when the cavity faces the first solution compartment, the conductive extension is configured parallel to the first electret, thereby inducing a charge gradient in the valve that attracts the charged molecules toward the cavity; and after the rotating step, the extension of the valve is parallel to the second electret, thereby inducing a charge gradient in the valve that repels the charged molecules from the cavity.

20. 20. The method of claim 19, wherein the valve comprises a plug movable relative to the barrier, the plug having a microchannel that allows fluid passage, and the transferring step comprises moving the plug relative to the barrier toward the inside of the first solution compartment, thereby reducing the volume of the first solution compartment and inducing a flow of the charged molecule through the microchannel into the second solution compartment.

21. 21. The method of claim 20, further comprising causing movement of the plug through expansion of a spring.

22. 21. The method of claim 20, further comprising causing movement of the plug through magnetic attraction between a first magnet attached to the plug and a second magnet fixed to an opposite end of the first compartment relative to the plug.

23. 21. The method of claim 20, further comprising causing movement of the plug through an electrostatic force induced between a first electrostatic charge attached to the plug and a second electrostatic charge fixed to an opposite end of the first compartment relative to the plug.

24. 21. The method of claim 20, wherein the plug is made of a conductive material.

25. 25. The method of claim 24, wherein the plurality of electrets comprises an electret layer configured in the first solution compartment, and the method further comprises, through the action of the electret layer: repelling the charged molecules from the end of the first solution compartment toward the plug, and inducing a dipole in the plug; and, after inducing the dipole in the plug, exerting an electrostatic force on the plug, thereby attracting the plug toward the electret layer, reducing the volume of the first solution compartment, and inducing a flow of the charged molecules through the microchannel to the second solution compartment.

26. The valve includes a plug having a microchannel that allows fluid to pass therethrough; the plug is made of a conductive material; and the plurality of electrets includes an electret layer configured in the first solution compartment, the electret layer configured to: (1) repel the charged molecules from the end of the first solution compartment toward the plug, and (2) induce a dipole within the plug; and the method further includes: receiving a sample in the first solution compartment above a sample holder comprising a plurality of beads having an electrical charge, the plurality of beads being bonded together with a dissolvable adhesive; dissolving the adhesive with a solution in the first solution compartment, thereby releasing the plurality of beads into the first solution compartment; and using the electret to induce movement of the charged molecules into the plug, diffusion of the charged molecules through the plug, and movement of the released beads into the plug.

18. The method of claim 17.

27. 18. The method of claim 17, further comprising degrading the biological material into double-stranded DNA or single-stranded DNA in the first solution compartment.

28. 18. The method of claim 17, further comprising testing the sample for the presence of a specific single-stranded DNA strand in the second solution compartment.

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