Protecting nanopore arrays with electrode connections from electrostatic discharge
By designing modular components, the electrode array and conductive structures are used to suppress electrostatic discharge, the problem of sensors being susceptible to damage in wet conditions is solved, and the performance and reliability of the equipment are improved.
Patent Information
- Application Number
- CN201980034038.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2018-05-24
- Filing Date
- 2019-05-08
- Publication Date
- 2025-02-28
- Estimated Expiration
- 2039-05-08
AI Technical Summary
Existing sensors are susceptible to uncontrolled voltages such as electrostatic discharge (ESD) in wet conditions, resulting in performance damage, and their sensitive properties prevent technicians from separating them into separate components, affecting the performance and reliability of the equipment.
A modular assembly is designed with an electrode array and a conductive structure or grid, through removable connection to the receiver, forming a microfluidic device that suppresses the conduction of electrostatic discharge and guides it away from the sensor area.
Effectively prevent electrostatic discharge from causing damage to the sensor, improves the performance and reliability of the equipment, enables the sensor to be used in an uncontrolled environment, and simplifies the maintenance and upgrade of the equipment.
Smart Images

Figure CN112154327B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to an assembly configured to engage and mate with a second assembly or a receiver. The assembly and the receiver together form a device. In particular, the present invention relates to an assembly having a sensor for sensing in wet conditions. The assembly and the receiver form a microfluidic device. Background Art
[0002] Such sensors are known from WO99 / 13101 and WO88 / 08534, wherein the sensor is provided in a dry state and a liquid test sample can be applied to the device and transported to the sensor area within the device by capillary flow. An array of a certain volume of polar medium can be used in the sensor to form a membrane array comprising amphiphilic molecules. The sensor may comprise a lipid bilayer. Other types of sensors are known, such as ion selective sensors comprising ion selective membranes.
[0003] After initial fabrication, the sensor is dry and the assembly can receive a liquid to form a membrane array, such as an array of a volume of polar media that can be used in a range of applications including forming a membrane comprising amphiphilic molecules.
[0004] Another example is provided by WO 2009 / 077734 which discloses a device for producing a layer of amphiphilic molecules.An analytical device combining components to provide an amphiphilic membrane and a nanopore for a sensor is also disclosed by WO 2012 / 042226.
[0005] Known sensors are incorporated into expensive test equipment that provides high performance analysis of sensor readings in a wide range of tests or applications. These complex devices have sensitive sensors that are protected by incorporation and packaging, and the data read from the sensors must be read quickly and efficiently.
[0006] Although the concept of separating the functionality of a device from one or more subcomponents is known, the sensitive nature of such sensors prevents technicians from separating the functionality as this may compromise the performance and / or reliability of the device. Furthermore, such sensitive and expensive devices are often reserved for laboratory use or other controlled conditions, and the use of specialized equipment in uncontrolled environments such as field use further discourages modification. Summary of the invention
[0007] Therefore, the object of the present invention is to provide an improved assembly with a sensor, the assembly being configured to prevent, for example, electrostatic discharge (ESD) from damaging the sensor. This assembly is modular so that it can be removably connected to a receiver to form a device. Subsequently, the device is removably connected to the equipment so that data from the sensor can be read and analyzed. Alternatively, the assembly can be removably directly connected to the equipment and removably directly connected from the equipment. The present invention generally lies in such modular assemblies. Alternatively, it can be provided as a kit with an assembly and a receiver or an assembly, a receiver and an apparatus.
[0008] In general, the present invention resides in an assembly configured to removably engage with a receiver, the assembly having an array of electrodes for engaging with a corresponding array of connectors on the receiver. A plurality of electrodes in the array (which may be a majority of the electrodes on the array) are electrically connected to corresponding recesses, which may be wells. To prevent any impairment of the performance of a sensor disposed in the well, a structure is utilized to protect the electrode array from uncontrolled or unadjustable voltages, such as electrostatic discharge (ESD). The structure, alone or in combination with the assembly, is used to at least partially electrically encapsulate the well or recess from the uncontrolled voltage.
[0009] According to one aspect, the invention resides in a component configured to removably engage with a receiver, the component having: an array of electrodes and configured to removably connect to a corresponding array of connectors on the receiver, wherein a plurality of electrodes in the array are electrically connected to corresponding grooves or wells, each groove forming part of a sensor for receiving a fluid therein, such that a membrane can be formed across each groove, which separates each groove, thereby separating the fluid in each groove from a conductive fluid in a common chamber.
[0010] The assembly has a conductive structure or grid that appears similar to a matrix configured to span the array to enable electrical connections between the array of electrodes and the array of connectors of the receiver, wherein the conductive structure is configured to suppress electrostatic discharge (ESD) conducted through the grooves and / or direct ESD away from the grooves. In other words, the connectors of the receiver extending from the receiver to connect to the electrodes extend through the grid. That is, each connector on the device reaches the pads on the assembly by passing between and through the grid walls.
[0011] The common electrode may be in contact with the fluid in the common chamber. The conductive structure may be electrically connected to the common electrode. The membrane may be an amphiphilic bilayer.
[0012] The assembly may have a conductive fluid in a common chamber and a fluid in a plurality of grooves. A membrane may be formed across the plurality of grooves to separate the fluid in the common chamber from the fluid in each of the plurality of grooves. The conductive structure may be configured to inhibit electrostatic discharge across or through the sensor or membrane via the grooves and / or direct electrostatic discharge away from the sensor or membrane. When the membrane is formed across the plurality of grooves, the fluids contained in the grooves are separated from each other.
[0013] Conductive structures may be connected to the fluid in the common chamber to suppress potential differences generated across the grooves or membranes.
[0014] The assembly may be substantially planar, extending from a proximal end to a distal end. The electrode array may be configured between the ends of the assembly. Alternatively, the connector array may be located at one of the ends of the assembly.
[0015] A common electrode may be disposed in the common sample chamber, and the grid may be connected to the common electrode.
[0016] The electrode array may be mounted on a substrate, such as a substrate for the well. Alternatively, the electrodes and / or well may be formed on a printed circuit board (PCB). PCBs may be cheaper and faster to manufacture.
[0017] The sensor may have a nanopore incorporated therein. The nanopore may be biological. The fluid may be a liquid that may span the well to form a lipid bilayer. The sensor may have a nanopore connecting the cis and trans regions within the assembly. The groove may support the membrane. The groove may be implemented in a solid state membrane and have a nanopore in the groove. The nanopore may be a biological nanopore or a synthetic nanopore.
[0018] The assembly may have a membrane formed across one groove or all grooves. The membrane may be a lipid bilayer. The grid may receive an ESD event and dissipate the energy of the ESD to prevent damage to the sensor and / or membrane.
[0019] The conductive structure has an aperture or frame through which the connector of the receiver extends to contact the electrode.The structure may be a mesh structure or net mounted on at least part of the base on which the electrode is formed.
[0020] The conductive structure may prevent contact with the electrode, in particular contact with a part of the body such as a finger or a gloved finger. However, contact with the electrode may occur, and if the finger or gloved finger contacts the electrode, the electrode should be sized so that the conductive structure is also contacted. In other words, only contact with the electrode is prevented.
[0021] The assembly may also have a membrane formed across a plurality of grooves.The conductive structure or grid may be configured to inhibit electrostatic discharge across the sensor or membrane via the grooves and / or direct electrostatic discharge away from the sensor or membrane.
[0022] The component can have a body surrounding, encircling or enclosing the groove, and the conductive structure is connected to the body so that they have the same potential difference. In other words, the body and the conductive structure can be used as a ground plane for the component. In use, the conductive structure acts to protect the groove and inhibit ESD from passing through the groove to the body of the conductive structure when a film is formed across the groove.
[0023] Each groove may contain a fluid, such as a liquid, which contacts the membrane disposed across each groove corresponding to a respective electrode in the array, wherein a conductive structure or grid is connected to the fluid reservoir to provide the fluid to the grooves to suppress a potential difference generated across the grooves or the membrane. The grid may be electrically connected to the body of the assembly to suppress a potential difference or voltage across the sensor and / or the membrane.
[0024] The assembly may or may not have a fluid supply. If there is no fluid supply and the membrane is pre-configured, the assembly may be said to be configured to prevent damage to the membrane and / or sensor.
[0025] The common sample chamber may contain an ionic fluid in contact with a common electrode. The fluid may provide a direct electrical connection between the connector array and the common electrode containing the fluid disposed in the upper sample chamber. ESD may be dissipated throughout the array, thereby minimizing its effects. The effects of the charge applied to the grid on the sensor components (e.g., membranes) in the grooves or wells may be suppressed or minimized because the grid and the fluid are connected via at least the common electrode and are present at the same potential, thereby suppressing the voltage across the well.
[0026] The electrode array may be arranged on a base substrate and the conductive structure may be mounted on the substrate. The electrode array mounted on the substrate may define a plane and the conductive structure may extend parallel to the plane. The conductive structure may extend above the substrate and above the electrode parallel to the plane so that a gap is created therebetween. Alternatively, the grid may be located in the same plane as the substrate. Forming the grid from the substrate may reduce costs because the grid, or more specifically, the grid walls may be formed with minimal material cost or minimal processing time. If the substrate is non-conductive, a conductive layer may be added to at least a portion of the exposed surface of the grid.
[0027] The conductive structure may extend from a plane defined by the electrodes. The electrode array may be arranged on a base of the substrate. At least a portion of the substrate may extend from the region between the electrodes to form a wall, and the conductive structure may be arranged on top of the wall. The conductive structure may be formed by depositing a conductive material in the region between the electrodes.
[0028] The conductive structure can be configured to partially surround each electrode. This can be achieved by forming a conductive electrode on each side of the electrode while enabling a connection from the receiver to contact the electrode. The cross-sectional shape of the conductive structure in the area away from the electrode can have a sharp edge or tip. Therefore, any charge from the ESD can be concentrated at the edge point.
[0029] The conductive structure may be configured as a grid and extend between the electrodes in a planar direction defined by the base or substrate.
[0030] The electrodes may be arranged in an array having a rectilinear pattern. The footprint of each electrode may be quadrilateral. Alternatively, the footprint may be one of a circle, a diamond, or a shape having 5 or more sides.
[0031] The cross-sectional profile of the grid wall may be rectangular. The top of the wall may have a non-flat profile, such as circular.
[0032] The cross section of the wall may taper outwardly to minimize the apertures in the grid or mesh or net, thereby further preventing contact with the electrodes. In this way, the surface area of the grid may be increased to provide a larger contact area for an object such as a finger.
[0033] The spacing of the electrodes in the array may be between 100um and 1500um. The spacing may be between 500um and 1000um, and preferably between 700um and 900um.
[0034] The thickness of the cross section of the wall of the conductive structure may be between a minimum of 10 um and a minimum of 200 um. The wall thickness may be between 25 um and 100 um.
[0035] The windows or apertures of the conductive structure through which the connector extends may have rounded corners. The rounded corners may reduce the inductive path between the grid and the common electrode.
[0036] The electrode array and the conductive structure may be at least partially covered with a removable protective film or layer to inhibit anti-static discharge. The film may be configured to minimize any triboelectric charge that may be generated by removing the film, which is required before the assembly and the receiver can be mated. The film may inhibit charge conduction through the groove and / or sensor or in the area of the groove and / or sensor through the conductive structure. Thus, the film and the conductive structure may act synergistically.
[0037] In another aspect, the invention resides in a kit having a component as claimed and a receiver, wherein the array of connectors on the receiver is configured to extend through the conductive structure without contacting the conductive structure to form an electrical connection with the electrodes on the component.
[0038] The grid can be connected to a conductive fluid in the sample chamber to suppress a potential difference generated across a groove or membrane formed between the fluid in the sample chamber and the fluid in the groove, so that when the conductive fluid occupies the sample chamber, ESD conduction through the groove and / or sensor or in the area of the groove and / or sensor is suppressed by the conductive structure.
[0039] The recesses or wells of the assembly may be provided with pores for reading the properties of a nucleotide passing through the pores.The pores may be nanopores in a membrane between the fluid in the sample chamber and the fluid in the at least one well.
[0040] The conductive structure may be formed as a grid having a plurality of apertures. The grid may have an aperture aligned with each of the mating connectors and electrodes. BRIEF DESCRIPTION OF THE DRAWINGS
[0041] The present invention is discussed below, by way of example only, with reference to the accompanying drawings, in which:
[0042] Figure 1 is a perspective view of a device having removably detachable components;
[0043] Figure 2 yes Figure 1 A schematic cross-sectional view of a device of FIG. 1 showing components removed from the device but ready for connection thereto;
[0044] Figure 3 is a cross-sectional view of a well having a known connection structure;
[0045] Figure 4 is a cross-sectional view of a well of a device having a polar dielectric layer;
[0046] Figure 5 is a cross-sectional view of another well of the device, which shows the ideal fluid behavior;
[0047] Figure 6 is a cross-sectional view of a well of a component having a through hole connected to an exposed pad located on an electrode array of the component;
[0048] Figure 7 is a cross-sectional view showing a schematic diagram of five wells of the assembly, each well connected to a pad and aligned with a corresponding connection of a receiver;
[0049] Figure 8is a cross-sectional view showing a schematic diagram of five wells of the assembly, two of which are connected to pads of an electrode array at the end of the assembly;
[0050] Fig. 9 is a schematic diagram of an electrode pad array having a grid inserted into and surrounding the pads, wherein the grid is connected to a ground electrode;
[0051] Fig.10 yes Fig. 9 A schematic end view of a grid in;
[0052] Fig.11a and 11b is a schematic diagram of a portion of a grid positioned adjacent to a pad of an electrode of an assembly and in the region of a well;
[0053] Fig.12 is a detailed view of an embodiment of the present invention in which a grid is positioned over an electrode array and connected to a ground electrode;
[0054] Fig.13 yes Fig.12 A detailed view of one corner of the embodiment shown in;
[0055] Fig.14 is a perspective view of an array of connectors configured to extend between the grids to contact an electrode array of the assembly;
[0056] Fig.15 yes Fig.15 A perspective view of the individual contacts of the connector shown in FIG.
[0057] Fig.16 is a perspective view of a section of a grid positioned over a section of an electrode array; and
[0058] Fig.17a and 17b Two examples of parts of alternative arrangements are shown respectively. DETAILED DESCRIPTION
[0059] Figure 1 An apparatus 2 is shown having a removably detachable device 4 having a receiver 6 and an assembly 8. The device is removably detachable from a base 10 of the apparatus 2. The various parts of the apparatus may be provided as a kit. The assembly 8 may be disposable. The device 4 may be inserted into and removed from the base 10. The assembly 8 may be inserted into and removed from the receiver 6.
[0060] exist Figure 2, the assembly 8 is shown positioned over the receiver 6 prior to insertion. Upon insertion, the assembly and receiver are mechanically connected and secured by latches 12 and grooves 14 located at the ends of the receiver. Electrically, the assembly and receiver may be connected via an array of electrodes 16 on the assembly 8 and a corresponding array of connectors 18 of the receiver 6. The body of the assembly 8 is typically made of a plastic material having a certain degree of elasticity. The plastic material may be, for example, polycarbonate.
[0061] Component 8 can be disposable, and for example, has a disposable flow trough located therein. The flow trough can be equivalent to the flow trough discussed in WO 2014 / 064443, which is incorporated herein by reference in its entirety, wherein the component is configured as a removable low-cost component that can be discarded after a single use. This is achieved by configuring the more expensive components of the device 4 in the receiver 6. The low-cost component makes it feasible to conduct multiple experiments relatively cheaply using different flow troughs. The base assembly 10 can accommodate the electronic equipment and cooling configuration of the overall device 2. The receiver 6 can accommodate other electronic equipment not included in the base 10 and is used as an adapter for receiving component 8.
[0062] Electrical connections are known from WO2009 / 077734, which is incorporated herein by reference in its entirety and provides an example of using a 'solder bump' approach to provide electrical connections to a layer of amphiphilic molecules. Figure 3 Such a 'solder bump' 20 connection as disclosed in WO2009 / 077734 is shown connected to a via 22 passing through a substrate 24 to a well electrode 26 at the bottom of a well or recess 28. The solder bump 20 makes a permanent connection to a support 30 connected to a microprocessor or similar controller (not shown).
[0063] Well 28 is formed in the substrate 24 of non-conductive material, and can be used to form or support the amphiphilic molecule layer. In use, an aqueous solution can be introduced into the well 28 and the area around it, so that an amphiphilic molecule layer is formed across the well 28, thereby separating the aqueous solution in the well 28 from the aqueous solution of the remaining volume above the groove. The arrangement of the well or groove 28, the well electrode 26 and the additional circuit system (not shown) realizes the measurement of the electrical signal across the amphiphilic molecule layer. The well electrode can be in electrical contact with the aqueous solution in the groove 28.
[0064] Figure 4 and 5Examples of recesses or wells 28 forming part of a sensor array are disclosed in WO 2014 / 064443 and WO 2013 / 121193, respectively, which are incorporated herein by reference in their entirety and describe that wells 28 are formed in a material 24 forming a body, such as SU-8, and that many wells 28 can be formed in close proximity within the material to form a sensor well array. These wells 28 allow electrical signals across the amphiphilic molecule layer 11 to be measured by connecting the circuit 26 to the contacts 22 and 25. The wells 28 known from WO 2014 / 064443 are preferably formed in a material 24 forming a body, such as SU-8, and that many wells 28 can be formed in close proximity within the material to form a sensor well array. Figure 4 A polar medium layer 32 is shown forming a meniscus contact surface 34a on the membrane 34, which protrudes into the well 28 to contact the polar medium. A common electrode 36 is arranged above the material 24 to make electrical contact with the polar medium layer 32 after the polar medium has been provided. The ratio of the volume of fluid in the well 28 to the volume of fluid in the layer above which the polar medium 32 is formed can be between about 1:100 and about 1:10000. It is known from WO2013 / 121193 that Figure 5 A schematic cross section through another microcavity or sensor well 28 of the sensor array is shown. In practice, an array of such sensor wells 28 formed in a body would be provided in an assembly of a device and further include a cover over the surface of the body to define a cavity between the cover and the body. Figure 5 ) is arranged in the cavity for connection to the circuit and acts as a common electrode for the wells in the array.
[0065] The grooves or wells 28 form part of the sensor and the sensing assembly must communicate with a reader or microprocessor. In the present invention, these wells are present in the assembly 8 and must communicate electrically with the receiver 6 and / or the reader on the base 10.
[0066] For example, removable connections or non-permanent electrical connections are known from WO2016 / 059417, which is incorporated herein by reference in its entirety and is suitable for arrays of electrical connections in such a way that component parts can be attached and detached, and optionally reattached thereafter, without requiring extreme conditions (whether chemical or environmental) to trigger the connection or release of the connection.
[0067] While removably detachable electrical connections are known, the inventors have recognized that conventional connections for parts such as the assembly 8 and the receiver 6 may be improved. Specifically, the contact surfaces may be improved to provide an additional layer of protection to the well or recess 28 and any sensor or sensing assembly present or formed in the recess 28. The contact surfaces connected to the well on the assembly are sensitive to mechanical and / or electrical shock.
[0068] Figure 6 By way of example, one well 28 of a sensor array having an electrode array 16 is shown. Each well 28 is connected by one of the electrical connectors in the array 16. A pad 100 is provided to enable connection to the well electrode 26 via a through hole 22. The pad 100 can be made of any conductive material, such as gold, copper or platinum. The substrate 24 acts as an insulator and is approximately 500 μm thick. The insulator can be made of, for example, silicon or glass. In an alternative embodiment of the present invention, the substrate can be conductive and have additional layers of insulating material or dielectrics to configure the pads, through holes and other such components.
[0069] Figure 7 and Figure 8 A receiver 6 is shown adjacent to an assembly 8, with portions of an electrode array 16 (five wells 28) aligned with an array of connectors 18. When connected and the assembly is configured for use, the signals detected by the well electrodes 26 in the wells 28 can be read. The signals are passed from the wells 28 via the well electrodes 26 through the through-holes 22 to the corresponding pads 100 of the electrode array 16, which are configured to contact the connectors on the array of connectors and provide the signals to a processor (typically an ASIC device). A common electrode 36 may be electrically connected to each well 28 through a polar medium 32 via a conductive diffusion layer 40 so that the processor can control which of the well sensors is read or sensed, despite multiplexing.
[0070] Figure 7 express Figure 2 The configuration shown in Figure 8 This represents an example where the array is configured at the end of the assembly 8 for engagement with an array of connectors located in recesses 14 of, for example, the receiver 6 .
[0071] The present invention is particularly suitable for protecting a membrane formed above a well or groove, which is susceptible to damage or rupture caused by uncontrolled voltages such as ESD flowing through the well or sensor. The membrane can be a layer formed by amphiphilic molecules such as phospholipids, which have both hydrophilic and lipophilic properties. The amphiphilic layer can be a monolayer or a bilayer. The amphiphilic layer can be a coblock polymer such as disclosed in Gonzalez-Perez et al., Langmuir, 2009, 25, 10447-10450 or WO2014 / 064444, which are incorporated herein by reference in their entirety.
[0072] The membrane may include an orifice formed in the solid layer, which may be referred to as a solid pore. The orifice may be a well, gap, channel, groove or slit disposed in the solid layer along which the analyte may be transferred or into which it may be transferred. Such solid layers are not of biological origin. The solid layer may be formed of both organic and inorganic materials, including but not limited to: insulating materials such as Si3N4, A12O3 and SiO; organic and inorganic polymers such as polyamides; plastics such as Teflonμ, or elastomers such as two-component addition-cured silicone rubber; and glass. The solid layer may be formed of graphene. Suitable graphene layers are disclosed in WO-2009 / 035647, WO-2011 / 046706 or WO-2012 / 138357. Suitable methods for preparing solid pore arrays are disclosed in WO-2016 / 187519.
[0073] The biological nanopore may be disposed in one or more membranes, thereby providing a conductive path across each membrane for fluidically connecting a fluid in a well disposed in the well array with a solution disposed in the upper chamber. The nanopore may be a transmembrane protein pore derived from, but not limited to, α-hemolysin, anthrax toxin and leukocidin, outer membrane proteins / porins of bacteria, such as Mycobacterium smegmatis porins and lysin. The pore may be derived from, for example, CsgG as disclosed in WO-2016 / 034591. The nanopore may be disposed in the orifice of a solid membrane. Such pores are referred to as hybrid pores. The nanopore may be formed by DNA origami.
[0074] The device of the present invention is particularly suitable for estimating the sequence of a polymer analyte. The analyte may be, for example, a polynucleotide, a polypeptide or a polysaccharide. The measurement of the polymer may be performed under a potential difference applied across the nanopore during the translocation of the polymer through the nanopore. The measurement may be a measurement of the ion flow through the nanopore during the translocation.
[0075] An ionic solution may be disposed in the wells in contact with each respective membrane in the array and an electrode disposed in each respective well.
[0076] The assembly 8 may be supplied with a polar medium which forms a meniscus or membrane above the wells 28 such that the nanopore is located in the membrane of each well 28. The meniscus cooperates with the wells to form part of the sensor. Alternatively, the assembly may be supplied 'dry' without the polar medium, which is added to the assembly before it is mounted in the device 6 and before the sample is tested or analyzed. Additionally, the assembly may be configured to have a solid membrane and / or solid state.
[0077] The meniscus and / or sensor of the trap are sensitive to uncontrolled voltages such as ESD. Therefore, the trap must be protected by suppressing voltage discharges across or through the trap. In use, the pads 100 of the electrode array 16 are exposed in preparation for engagement with the connector array 18 on the device. Although the components 8 can be connected to the device 6 without touching the pads, they are still susceptible to accidental touches such as fingertips. In the field, which is the opposite of controlled laboratory conditions, the user will typically remove the component from the packaging and manually place it in the receiver. The present invention mitigates any harmful effects of the user contacting the electrode array 16 with, for example, their fingertips.
[0078] For illustrative purposes, Fig. 9 An array of pads 100 in the electrode array 16 is shown. A conductive structure 102 or grid is configured to span the electrode array 16. The conductive structure or grid includes a common pad 104 connected to a common electrode 36. The grid 102 can form a mesh or mesh structure connected to the common electrode. For example, the grid 102 is connected to the common electrode 36 for electrically connecting the grid to the polar medium 32 in the chamber above the well.
[0079] Additionally or alternatively, the grid can be connected to the polar medium 32 or a chamber in which the polar medium is present, and this connection can be made by at least one of the following: a dedicated through hole; a wired or bonded connection to a portion of the substrate; an electrical connection through the body of the component 8; or an electrical connection to a structure that forms a chamber that holds the polar medium 32, which structure surrounds the well 28 of the array 16. Fig.10 A cross-sectional view of a section of the grid 102 positioned above the array 16 is shown, and Fig.11a The relationship between the grid 102 and the polar medium 32 or sample 32 is shown. In the example shown, the grid extends from an area on the substrate between the pads, but does not contact the pads 100, and extends above the surface of the substrate. In the example shown, the grid forms a web across the surface. However, the grid can be formed by a wall surrounding one or more pads 100. The grid 102 can be positioned across Figure 7 , where the electrode array 16 can be arranged on the surface between the ends of the component 8 and can be positioned to span Figure 8 An electrode array 16 is shown in FIG. 1 , wherein the array 16 is arranged at an end region or surface of the component.
[0080] Fig.11bAn alternative example is shown in which the substrate 24 is conductive and an insulating layer or dielectric surrounds the substrate so that the well electrode 26, the via 22, and the pad 100 can be configured on the substrate. The grid 102 can be connected to a conductive coating surrounding or covering a portion of the substrate or the body of the component 8. In this way, the charge transferred to the grid is conducted between the grid and the conductive surface formed on the dielectric and dissipated into the dielectric, which may produce a common field that affects both the common electrode and the well electrode.
[0081] The grid can also be connected to the ground plane of the components and the device once the components are mounted in the device 6. In other words, if the substrate is conductive and coated in a dielectric or insulator, the grid can dissipate the charge into this capacitance, the field of which affects both the common electrode and the well electrode.
[0082] The dimensions of the pads and surrounding grid are such that (i) an object, such as a finger, is prevented from contacting the array 16 because the grid acts as a barrier, or (ii) if the array 16 is contacted by an object, it contacts the grid first. Thus, if any charge accumulated on a user's hand or a tool held by the user in the area of the electrode array 16 approaches or contacts the component 8, it is inhibited from passing through the well 28 or well electrode 26 area because it is directed through or via the grid 102 to the common electrode 36.
[0083] Because the grid 102 and the polar medium 32 are electrically connected, the energy transmitted from the ESD to the grid and to the polar medium needs to complete negligible work, so that the voltage across the well 28 is negligible. In use, the polar medium layer 32, which may contain the sample to be analyzed, is electrically connected to the common electrode 36 via the conductive diffusion layer 40. Therefore, if an ESD is applied to the grid, the potential difference between the grid 102, the common pad 104, the common electrode 36, the conductive diffusion layer 40 and the polar medium 32 or the sample is negligible. This is because the charge is distributed on these components, which inhibits any charge from being transferred between the electrode pad 100 and the well 28 to the sample of the polar solution when contacting the grid or contacting both the grid and the pad. The sensor and / or membrane forming or forming part of the well 28 is protected from ESD to the array 16. The grid 102 acts as a mechanical and / or electrical shield that can be connected to a substantially large volume of fluid (i.e., the polar medium 32). These elements of assembly 8 are significantly larger than the size of well 28 or the volume of the fluid contained in the well by at least 2 orders of magnitude. As described above, the ratio of the volume of the fluid in well 28 to the volume of the fluid in the layer forming the polar medium 32 above it can be between about 1:100 and about 1:10000. In an example, the volume of the common cell chamber or sample chamber for accommodating the polar medium 32 and the associated common medium chamber is about 135ul. In an example of an array with 130 electrodes, the fluid occupies 126 electrodes for forming a film between each well and the sample chamber above, and the total volume of the fluid in the well is about 0.9ul. The ratio in the example is about 1:150. In this way, the volume of the grid and / or polar medium (which is significantly larger than all the wells together) is used as a buffer or insulator to protect the sensing elements and sensor elements of the wells therein from ESD or similar uncontrolled charges. In other words, any uncontrolled charge or ESD is inhibited from being conducted from pad 100 to well 28 because grid 102 prohibits contact with the pad and / or prohibits contact with the pad without contacting the grid, so that (i) the charge, such as ESD, is transferred to a polar medium or sample, thereby distributing the charge with low energy consumption so that the potential difference between pad 100 and well 28 is negligible, or (ii) if array 16 is contacted, the ESD charge is prohibited from flowing through well 28 because grid 102 has already been contacted so that the well 28 area and the grid have the same potential difference - the charge is already balanced.
[0084] In use, the components are encapsulated in a material that inhibits charge accumulation to minimize the risk of damage to the sensor or membrane within the well 28, which might occur if the pads 100 of the electrode array 16 were touched. In field use, outside of a controlled environment such as a laboratory, there are few facilities such as grounding points or grounding straps to divert uncontrolled voltage or ESD away from the pads.
[0085] To illustrate the dimensions of the present invention, by way of example, a fingertip 106 is shown in Figure 11 adjacent to the grid 102. If an object, such as a user's finger, approaches the pad 100, contact with the pad is prevented, and even if contact is made, the finger will touch the grid before, during, and after contact with the pad 100.
[0086] After initial fabrication of assembly 8 and prior to filling with a conductive fluid such as polar medium 32 , grid 102 is configured to protect any sensors that will subsequently be formed in well 28 .
[0087] Fig.12 and 13 1 is a snapshot of a CAD image of an embodiment of a grid 102 positioned between pads 100 and connected to a common pad 104. The size of the array 16 is approximately 130 pads, equivalent to an array of approximately 13 pads multiplied by approximately 10 pads. For example, the spacing between the pads is shown as 800um. The pads are approximately square with a side length of approximately 710um. The gap between the pad 100 and the grid is approximately 30um. The thickness of the grid wall is approximately 30um. The ratio of the thickness of the grid wall to the width of the pad is approximately 1:25. The ratio can be between approximately 1:10 and approximately 1:100. The size of the distance between the grid walls or between the sides of the opening can be set to prevent the finger from being able to contact the pad without contacting the grid. Through the guide, the maximum opening size can be approximately 2mm between the corners of the pad.
[0088] Fig.13 yes Fig.12 FIG. 1 is an enlarged view of the lower right hand side of the array 16 in FIG. 1. It should be noted that the shape of the grid 102 in the area around the individual pads corresponds or matches the shape of the pads. The shape of the grid in the area adjacent to the corners of the pads is curved. The shape of the grid is configured to minimize the inductance between the common pad 104 and any point on the grid 102.
[0089] A gap is provided between the pad 100 and the grid 102. The grid has been illustrated in other figures as an extension of the substrate, preferably grown from the substrate on which the pad 100 is formed, which cannot be seen from the Fig.12 and 13 The top surface of the grid has a conductive surface connected to the common pad 104.
[0090] Alternatively, the grid may be flush with the surface of the array so that rather than preventing a finger from contacting the pad, a finger is prevented from contacting the pad 100 without touching the grid.
[0091] The array 16 may additionally be covered by a protective antistatic tape (not shown) that may be removed from the array 16 on the assembly 8 prior to insertion into and connection with the receptacle 6. Without the grid 102, such tape, when peeled from the array 16, may generate triboelectric charges and damage the sensing function in the well 28. However, since the tape is connected to the grid, the tape complements the function of the grid 102, since any triboelectric charges generated by its removal will not affect the sensing in the well. Thus, the conductive structure is at least partially covered with a removable protective conductive film or protective layer.
[0092] A mechanical connection may be provided for engaging electrodes on the assembly 8 , such as spring-leaf metal contacts located on the receiver 6 . Fig.14 and 15 An example of a first array of connectors 108 with a pitch of 800 um is illustrated. Fig.15 A close-up of the connectors 108 are shown, which are spring loaded and disposed in respective recesses 110. To increase their strength, each connector tapers outwardly toward its base. The connectors are 100um thick and protrude to a height of 800um above the recess. The connectors are advantageously spring loaded and protrude from the base to facilitate their connection to the electrode array 16 under applied force.
[0093] Fig.16 A schematic perspective view of a portion of a segment of a grid 102 is shown. Fig.10 The diagram shows a cross section of the indicator grid 102 similar to a mesh resting on legs or walls extending from the substrate, while Fig.16 The grid is shown to have walls of pads 100 surrounding the electrodes. The examples shown herein have a grid surrounding each pad 100 on the array 16, but the grid may alternatively surround groups of pads. Thus, the grid may extend from the area on the substrate between the pads, but not contacting the pads 100, and form a wall. The top of the wall may be coated with a conductive material, such as gold or platinum, to conduct ESD away from the pads. Alternatively, the grid may have a non-convex profile and be approximately in the plane of the electrode array.
[0094] like Fig.16 As shown in , the height of the grid above the substrate (whether in mesh or wall form) is determined by the height of the connector 108. Fig.14 and 15In the embodiment of the present invention, the height of the contacts is about 800um, and when the assembly 8 and the device 6 are mated, the height of the contacts will generally decrease when compressed on the pads. For example, after mating, the height can be reduced by 25% to about 600um by compression. Therefore, the height of the grid above the surface can be about 500um, thereby preventing the grid from contacting the array of connectors 18 on the device. During mating, the connectors 108 extend through the grid and between the meshes or between the walls to contact the pads 100. The gap between the pads 100 and the walls of the grid 102 insulates the electrode array from the grid 102.
[0095] As described above, the shape and configuration of the grid is such that the inductance between the grid 102 , the common pad 104 , and the common electrode 32 is minimized.
[0096] The electrode array 16 and / or grid 102 have been described as being formed on a substrate 24 having conductive surfaces for pads 100 and for connecting to, for example, common electrode 36 .
[0097] The purpose of the assembly is to provide a low-cost single-use device, and various low-cost manufacturing techniques may be suitable for use with the examples in accordance with the teachings herein. Fig.17a and 17b Two examples of electrode arrays 16 for connection to a device 6 having a multi-layer and a single-layer substrate are shown, respectively. Fig.13 In the example shown in , the density of wells and electrodes is higher and has been fabricated on a substrate having a coating of electrodes and vias etc.
[0098] Alternatively, the pads 100 and grids 102 or traces may be formed by using the following methods:
[0099] Silicon wafer manufacturing, which can provide a minimum grid width as small as 5um, where the gap between the pad and the grid is 5um;
[0100] Glass wafer manufacturing, which can provide a minimum grid width as small as 10um, with a gap of 10um between the pad and the grid;
[0101] Printed circuit boards that can provide a minimum grid width as small as 50um, with a gap of 50um between the pad and the grid;
[0102] High-resolution printed circuit boards that can provide a minimum grid width as small as 3um, with a gap of 5um between pad and grid;
[0103] Conductive ink, inkjet printed on card or polymer, which can provide a minimum grid width as small as 150um with a gap of 50um between pad and grid;
[0104] Screen printing of conductive ink on card or polymer which can provide a minimum grid width as small as 20um with a 20um gap between pad and grid; and
[0105] Conductive material is sputtered on the card or polymer, which can provide a minimum grid width as small as 10um, with a gap of 10um between the pad and the grid.
[0106] For example, inkjet-printed, roller-coated digital microfluidic devices for cheap, miniaturized diagnostic tests are known from the paper by Dixon et al. [Lab Chip, 2016, 16, 4560].
[0107] exist Fig.17a , an electrode array 16 is arranged at the side of the assembly. In this example, the assembly is formed on a multilayer printed circuit board. The pads are printed on the exposed layer and surrounded by a grid 102 that can be connected to a common electrode (not shown in this figure). Traces 112 are shown as dashed lines because they are provided on another layer and lead from a through hole 22 connected to the pad 100 to a well 28 located on the other side of the PCB. Reducing the number of wells 28 can reduce the complexity of the structure required to encapsulate the wells and simplify the circuitry required to connect the wells to the device 6 via the array 16.
[0108] Fig.17b A further simplified arrangement is shown in which the connections to the pads 100 are arranged on a single layer substrate. The grid 102 continues substantially around the pads to prevent damage caused by ESD. In this particular configuration, the single layer substrate and printed traces enable components to be formed on the device.
[0109] Like numbers in the drawings represent like features. The present invention is described above by way of example only and may be modified within the spirit and scope of the present invention, which extends to equivalents of the features described and combinations of one or more features described herein. The present invention also lies in any individual feature described or implied herein.
[0110] Features list:
[0111] 2 Equipment 30 Support
[0112] 4 Device 32 Polar dielectric layer
[0113] 6 Receiver 34 Meniscus / Membrane
[0114] 8 Component 34a Membrane
[0115] 10 base 36 common electrode
[0116] 12 Latch 40 Conductive diffusion layer
[0117] 14 Groove 100 Gasket
[0118] 16 Electrode array 102 Grid / conductive structure
[0119] 18 Connector array 104 Common pad
[0120] 20 solder bumps 106 fingertips
[0121] 22 through hole 108 connector
[0122] 24 substrate 110 groove
[0123] 26 Well electrode 112 trace
[0124] 28 Wells / Grooves
Claims
1. A sensing assembly (8) configured to be removably engaged with a receiver (6), the assembly (8) comprising: a substrate (24) comprising a plurality of wells (28); a plurality of well electrodes (26) in respective wells (28); a common chamber above the wells (28) comprising a common electrode (36), wherein each well (28) forms part of a sensor for receiving a fluid, wherein a membrane (34) can be formed across each well (28) to separate the fluid in the well (28) from the fluid (32) in the common chamber; and an electrode array (16) configured to be removably connected to a corresponding array of connectors (18) on the receiver (6), wherein each electrode in the electrode array (16) is electrically connected to a corresponding well electrode (26) via a corresponding through hole (22) passing through the substrate (24), Characterized in that a conductive structure is configured to span the electrode array (16) to enable an electrical connection to be established between the electrode array (16) and a connector array (18) of a receiver (6), and is configured to suppress electrostatic discharge conducted through the well (28) and / or to guide the electrostatic discharge away from the well (28) through the conductive structure.
2. The sensing assembly (8) of claim 1 further comprising a conductive fluid (32) in the common chamber, wherein the fluid is in contact with a common electrode, and further comprising a fluid in the plurality of wells (28), wherein a membrane (34) is formed across each of the plurality of wells (28) to separate the fluid in the common chamber from the fluid in each of the plurality of wells (28), and wherein the conductive structure is configured to suppress electrostatic discharge across the membrane (34) via the wells (28) and / or direct electrostatic discharge away from the membrane (34).
3. The sensing assembly (8) of claim 2, wherein the conductive structure is connected to the fluid in the common chamber to suppress a potential difference generated across the well (28) or membrane (34).
4. The sensing assembly (8) according to claim 2, wherein the membrane (34) is formed by a layer of amphiphilic molecules.
5. The sensing assembly (8) according to claim 2, wherein a nanopore is provided in the membrane (34).
6. A sensing assembly (8) according to claim 5, wherein the conductive structure is formed by deposition of conductive material in areas between electrodes of the electrode array (16).
7. A sensing assembly (8) according to any preceding claim, wherein the conductive structure is configured as a grid and extends between electrodes of the electrode array (16) in a planar direction defined by the substrate.
8. The sensing assembly (8) according to claim 7, wherein: The grid is inserted between the arrays of electrodes of the electrode array (16).
9. The sensing assembly (8) according to claim 8, wherein: The grid extends from regions of the substrate between electrodes of the electrode array (16) and extends over the surface of the substrate (24).
10. The sensing assembly (8) according to any one of claims 1 to 6, wherein: The conductive structure is configured to span the electrode array (16) to enable an electrical connection to be established between the electrode array (16) and a connector array (18) of a receiver (6), wherein the connectors (108) of the connector array (18) extend through the conductive structure.
11. The sensing assembly (8) according to any one of claims 1 to 6, wherein: The conductive structure is electrically connected to the common electrode (36).
12. The sensing assembly (8) according to any one of claims 1 to 6, wherein the pitch of the electrodes of the array is between 100 um and 1500 um.
13. The sensing assembly (8) according to any one of claims 1 to 6, wherein the electrode array (16) and the conductive structure are at least partially covered with a removable protective film or layer.
14. A sensing kit having a sensing assembly according to any preceding claim and a receiver (6).
15. A sensing kit according to claim 14, wherein the array of connectors (18) on the receiver (6) is configured to extend through the conductive structure without contacting the conductive structure to form electrical connections with electrodes of the electrode array (16) on the component (8).
16. A sensing kit according to claim 14 or 15, wherein the conductive structure is connected to the conductive fluid in the common chamber to suppress the potential difference generated across the well (28) or membrane formed between the fluid in the common chamber and the fluid in the well (28), so that when the conductive fluid occupies the common chamber, electrostatic discharge is suppressed from being conducted through the well (28) by the conductive structure.
Citation Information
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