Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
  • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
  • G01N27/403—Cells and electrode assemblies
  • G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B81—MICROSTRUCTURAL TECHNOLOGY
  • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
  • B81B7/00—Microstructural systems; Auxiliary parts of microstructural devices or systems
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
  • H01L21/00—Processes or apparatus adapted for the manufacture or treatment of semiconductor or solid state devices or of parts thereof
  • H01L21/70—Manufacture or treatment of devices consisting of a plurality of solid state components formed in or on a common substrate or of parts thereof; Manufacture of integrated circuit devices or of parts thereof
  • H01L21/77—Manufacture or treatment of devices consisting of a plurality of solid state components or integrated circuits formed in, or on, a common substrate
  • H01L21/78—Manufacture or treatment of devices consisting of a plurality of solid state components or integrated circuits formed in, or on, a common substrate with subsequent division of the substrate into plural individual devices
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
  • H01L23/00—Details of semiconductor or other solid state devices
  • H01L23/28—Encapsulations, e.g. encapsulating layers, coatings, e.g. for protection
  • H01L23/31—Encapsulations, e.g. encapsulating layers, coatings, e.g. for protection characterised by the arrangement or shape
  • H01L23/3157—Partial encapsulation or coating
• • H—ELECTRICITY
  • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
  • H10D—INORGANIC ELECTRIC SEMICONDUCTOR DEVICES
  • H10D86/00—Integrated devices formed in or on insulating or conducting substrates, e.g. formed in silicon-on-insulator [SOI] substrates or on stainless steel or glass substrates
  • H10D86/201—Integrated devices formed in or on insulating or conducting substrates, e.g. formed in silicon-on-insulator [SOI] substrates or on stainless steel or glass substrates the substrates comprising an insulating layer on a semiconductor body, e.g. SOI
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
  • H01L2224/00—Indexing scheme for arrangements for connecting or disconnecting semiconductor or solid-state bodies and methods related thereto as covered by H01L24/00
  • H01L2224/01—Means for bonding being attached to, or being formed on, the surface to be connected, e.g. chip-to-package, die-attach, "first-level" interconnects; Manufacturing methods related thereto
  • H01L2224/02—Bonding areas; Manufacturing methods related thereto
  • H01L2224/04—Structure, shape, material or disposition of the bonding areas prior to the connecting process
  • H01L2224/05—Structure, shape, material or disposition of the bonding areas prior to the connecting process of an individual bonding area
  • H01L2224/0554—External layer
  • H01L2224/0555—Shape
  • H01L2224/05552—Shape in top view
  • H01L2224/05554—Shape in top view being square
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
  • H01L2224/00—Indexing scheme for arrangements for connecting or disconnecting semiconductor or solid-state bodies and methods related thereto as covered by H01L24/00
  • H01L2224/01—Means for bonding being attached to, or being formed on, the surface to be connected, e.g. chip-to-package, die-attach, "first-level" interconnects; Manufacturing methods related thereto
  • H01L2224/42—Wire connectors; Manufacturing methods related thereto
  • H01L2224/47—Structure, shape, material or disposition of the wire connectors after the connecting process
  • H01L2224/48—Structure, shape, material or disposition of the wire connectors after the connecting process of an individual wire connector
  • H01L2224/4805—Shape
  • H01L2224/4809—Loop shape
  • H01L2224/48091—Arched
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
  • H01L2224/00—Indexing scheme for arrangements for connecting or disconnecting semiconductor or solid-state bodies and methods related thereto as covered by H01L24/00
  • H01L2224/80—Methods for connecting semiconductor or other solid state bodies using means for bonding being attached to, or being formed on, the surface to be connected
  • H01L2224/85—Methods for connecting semiconductor or other solid state bodies using means for bonding being attached to, or being formed on, the surface to be connected using a wire connector
  • H01L2224/85909—Post-treatment of the connector or wire bonding area
  • H01L2224/8592—Applying permanent coating, e.g. protective coating
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
  • H01L2924/00—Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
  • H01L2924/15—Details of package parts other than the semiconductor or other solid state devices to be connected
  • H01L2924/161—Cap
  • H01L2924/162—Disposition
  • H01L2924/16235—Connecting to a semiconductor or solid-state bodies, i.e. cap-to-chip

Definitions

• the present invention relates to an ion sensor based on differential measurement and the manufacturing method thereof.
• Said sensor measures the concentration of certain ions of a solution by means of ISFET transistors (ion-selective field effect transistor) and compares said measurement with that of a reference solution stored in a microdeposit, said measurement being performed by an ISFET transistor. whose door is kept in contact with said reference solution, also called the REFET transistor (field effect transistor that does not respond to the ion concentration), and therefore presents a null response to the ions to be measured.
• ISFET transistors ion-selective field effect transistor
• the technical field in which the present invention is framed is that of the physical technology sector and its most common application is for the measurement of ions, for example of pH (concentration of hydrogen ions in a solution), in various sectors such as Food and biomedicine.
• test strips are strips of paper with different zones that are colored in contact with aqueous solutions, taking different colors depending on the concentration of specific ions of the measurement solution.
• concentration of the ions in the solution after wetting the strip with it, the user must compare the colors obtained with those of a table provided by the manufacturer.
• the result of this measurement technique depends very much on the correct manipulation by the user and on factors such as: the presence of proteins in the sample, the reaction time of the strip with the sample, or the homogeneity of the sample. An incorrect manipulation generates many false results (positive and negative).
• the resolution of this technique is considered generally it is 0.5 units, for the specific case of the pH measurement, which lacks sufficient diagnostic value to make clinical decisions in some biomedical applications such as in Urolithiasis (Kwong T. et al. "Accuracy of uri ⁇ e pH testing in a regional metabolic renal clinic: is the dipstick enough ?. Urolithiasis 2013).
• Ion Selective Electrodes are used for simpler measurements in terms of equipment and are less expensive. These electrodes consist of a selective membrane so that through the exchange or interaction of the ions of the solution with the membrane, the activity of the ion is converted into an electrical potential.
• the selective membrane can be of various types, glass, crystalline or based on ion exchange compounds. The latter consist of a polymer (for example, polyvinyl chloride, PVC) that immobilizes the ion selective compound.
• the measurement of the electrical potential of the ISEs requires the use of a reference electrode, which is often integrated into the same body of the ISE (combined electrodes).
• the reference electrode is generally a metallic electrode immersed in a reference solution which in turn is connected to the solution to be measured through a liquid joint.
• the main characteristic of the reference electrode is that its potential, that is, the potential between the inside of the metal and the sine of the solution in which it is submerged, does not depend on the composition of said solution. Reference electrodes usually have losses of reference solution through the liquid junction, so they need periodic refilling.
• these electrodes require a previous calibration consisting of the measurement of the potential generated when the electrode is immersed in a solution of known ionic concentration.
• These electrodes are part of an instrument, which in the case of pH is known as a pH meter, which is not cheap to manufacture, portable, or autonomous, and requires specific maintenance and cleaning conditions for proper conservation.
• the result of this measurement technique also depends on the correct manipulation by the user (who must be properly trained for that purpose). Incorrect handling or preservation of the electrodes can generate false results.
• ISFET ion selective field effect transistor
• the solution potential (which is the gate potential of the transistor) is controlled by a reference electrode such as those used for measurement with ISE type electrodes.
• the ISFET is a field effect transistor whose threshold voltage varies with the ion concentration of the solution that is in contact with its gate dielectric.
• the threshold voltage variation of the ISFET depends mainly on the H + ion, and is therefore used as a pH sensor.
• an additional layer called selective membrane is deposited on the door dielectric layer as described in US5250168.
• the ISFET will function as a sensor for some specific ions or others.
• the measurement with these sensors consists in recording the threshold voltage changes of the field effect transistor, which are proportional to the changes in the ion concentration that are to be measured.
• One way to measure the ISFET threshold voltage changes is by means of a circuit that polarizes the device with a constant drain current and a constant source drain voltage. In this way, the changes in the door voltage applied by the circuit to maintain said polarization are equal to the changes in threshold voltage suffered by the ISFET. Therefore, the gate voltage applied by the circuit is taken as the output signal.
• Both ISE electrode-based and ISFET-based measurement systems require a reference electrode to be able to measure ions. This makes them expensive and requires periodic maintenance.
• a solution for pH measurement was described with ISFET-type devices without reference electrode (PA Comte and J. Janata, "A field effect transistor as a solid-state reference electrode", Analytica Chimica Acta) consisting of the differential measurement of an ISFET and a REFET.
• the REFET is constituted by an ISFET whose door is kept exposed to a constant pH.
• the differential measurement consists in measuring the changes in threshold voltage of both devices using a single electrode immersed in the solution as a gate terminal and obtaining the response as a subtraction of the two values obtained.
• the REFET door is kept exposed at a constant pH by incorporating a microdeposit full of reference solution (internal solution).
• Said microdeposit is connected to the outside by means of a microchannel that acts as a liquid junction, so that the potential difference between the external and the reference solution is small and is little influenced by the pH or the concentration of other ions in the solution Exterior.
• the potential changes that occur between the electrode and the solution are transferred to both threshold voltage values, and therefore have no impact on the differential value (they are canceled in the subtraction operation). For this reason, this differential measurement system can be implemented with any conductive electrode, without the need for reference. Since the REFET is exposed to a constant pH solution, the variation in the differential value will be equivalent to the ISFET response to the pH change.
• the way to manufacture the REFET described by Compte and Janata is difficult to automate, and therefore would not allow the sensors to be manufactured at a much lower cost than the ISFETs with reference electrode, which would not allow their price to be affordable to the general public.
• the REFET microdeposit is constructed with an epoxy resin. This microdeposit, once the resin has cured, is filled with an agarose gel prepared in buffer solution. Subsequently, a vitreous capillary, which acts as a microchannel, is introduced into the agarose gel and the microdeposit is sealed with a layer of epoxy resin.
• the microdeposition buffer solution evaporates slowly through the microchannel, being replaced by air.
• the presence of air inside the microdeposit prevents it from functioning properly when it is used again after a prolonged time of immersion in aqueous solution. This is due to the fact that the filling with water, as well as the necessary diffusion of the air trapped outside, is done only through the microchannel, which is not filled with hydrogel.
• the lifetime of this type of sensor depends on the volume of the microdeposit and the dimensions of the microchannel that connects it to the outside, since the reference solution in the microdeposit will be diluted and contaminated through the microchannel, so that the error in the measurement may increase progressively as the pH of said solution varies with respect to its original value.
• EP 85200263 describes a sensor in which two ISFET sensors are used, one of which is located inside a conduit through which the reference solution is flowed. In this way, the aforementioned ISFET is always in contact with uncontaminated solution. However, it is necessary to incorporate into the sensor an injection system of the reference solution as well as feeding means of the injection system that make the described solution more complex and expensive.
• test strips are not very precise; glass electrodes are expensive, fragile, require maintenance and are little miniaturizable; the current ISFET and ISE type sensors are miniaturizable but are expensive and require maintenance because they have to be used with a reference electrode;
• the ISFET-REFET sensor proposed by Compte and Janata is expensive to manufacture and has a short life time; and the sensor described in EP 85200263, in addition to being two ISFET transistors, has a higher cost and complexity due to the need to have a reference solution injection system.
• the present invention describes a novel ion sensor based on differential measurement comprising at least one ISFET transistor and a REFET transistor.
• the REFET is defined by a structure composed of an ISFET covered by a micro tank where an internal reference solution is contained.
• a second object of the present invention is the method of manufacturing the previously described sensor that allows its mass production at low cost.
• a third object of the present invention is the previously described sensor immersed in a conditioning vessel filled with the reference solution, which makes it possible to extend the life of said sensor.
• the first object of the present invention is an ion sensor based on differential measurement.
• Said sensor is characterized in that it at least comprises: • a first ion selective field effect transistor and at least a second ion selective field effect transistor, electrically connected by means of connection tracks to a measurement circuit;
• the chips will preferably be of a semiconductor material
• the sensor described herein integrates a single REFET and a plurality of selective ISFETs each to a different ion. This is achieved by having a series of selective membranes arranged in each ISFET so that each of them detects a different ion. Both the ISFET and the REFET can be on the same chip or on different chips, but all ISFETs perform the differential measurement with respect to the same REFET. This is done with a single sensor, a plurality of measurements of concentrations of different ions at the same time.
• the reference solution is contained in a hydrogel that occupies the volume of the microdeposit and the microchannel.
• the REFET is preferably constructed from a selective ISFET to the H + ion, the reference solution being a buffer that sets the pH to a certain value, but it is also proposed that the REFET be constructed from a selective ISFET to another ion, that is to say, including a selective membrane to said ion on its door dielectric, in which case the reference solution must contain a certain concentration of that ion.
• the first ion selective field effect transistor is integrated into a first chip and at least a second ion selective field effect transistor is integrated into a second chip. If there are a plurality of second transistors, each of them can be integrated into a separate chip or they can all be integrated together into a single chip. In another particular embodiment of the invention, it is also provided that the first ion selective field effect transistor and the at least a second ion selective field effect transistor are integrated into the same chip. This reduces the time and manufacturing costs of the sensor. In another particular embodiment of the invention, the field effect transistors, the connection tracks, the electrode and a part of the measurement circuit are integrated in the same chip. This reduces the manufacturing costs of the sensor further and reduces its size considerably, which may be important for certain applications.
• connection of the chips, more specifically of the "connection pads" of the chips, with the connection tracks is carried out by wire welding.
• the chips are encapsulated by a polymer, the wires and the connecting tracks being covered by said polymer and the doors of the first and second ion-selective field effect transistor being discovered, the output of the microchannel and the electrode.
• the external walls of the microdeposit of the first transistor are, at least partially, of a material permeable to water molecules in the gas and air phase but not to the solution with the pH of reference.
• the diffusion of the air molecules to the outside and the water molecules to the interior is carried out throughout the surface of said permeable material accelerating the process of tuning the sensor when it will be used after a period in which it has not been used.
• This allows storage in Drying of the sensor and rapid rehydration of the microdeposit before use by immersion in a conditioning solution. This obviously greatly extends the life of this type of sensors.
• an ion selective membrane is placed on the door of the at least one second transistor (ISFET).
• the ion sensor based on differential measurement object of the present invention can measure concentrations of different ions.
• sensors can be obtained to measure concentrations of different ions such as Ca2 +, K +, Na +, Cl-, NH4 + or C032-.
• the microdepository has a volume between 0.001 mm3 and 1 mm3 and the microchannel has a section between 1 square micrometer and 10,000 square micrometers and a length between 10 microns and 1 mm.
• the concentration of chemical species inside the microdeposit follows an exponential evolution as these species diffuse through the microchannel outwards.
• the time constant of this concentration variation is proportional to the section of the microchannel and inversely proportional to the volume of the microdeposit and the length of the microchannel.
• the time it takes to lose a certain amount of the chemical compounds in the buffer that maintain the concentration of ions in the solution inside the microdeposit and the degree of contamination of said solution with compounds from outside is proportional to the microchannel section and inversely proportional to the volume of the microdeposit and the length of the microchannel. That is, a longer and / or thinner microchannel provides a stable sensor signal for a longer time. However, a longer and thinner channel also implies an electrical resistance of the microchannel filled with greater solution. Since the microchannel must electrically connect the solution inside the tank with the solution outside to transmit the electrode potential to the REFET transistor door, the greater the resistance of the microchannel, the greater the susceptibility of the sensor to electrical interference.
• microchannels that connect the microdeposit with the outside. Increasing the number of microchannels can reduce their section without increasing the electrical resistance between the solution of the microdeposit and the solution to be measured. A sufficiently reduced section of the microchannels prevents the entry of certain microorganisms into the microdeposit that could alter the characteristics of the reference solution or the surface of the REFET door dielectric.
• external and removable sealing means such as adhesive tape or the like, be provided at the outlet of the microchannel to seal the contents of the reservoir and the microchannel.
• the adhesive tape has the proper shape to be able to be removed manually. This allows to extend the life of the sensor since the solution inside the REFET is isolated, preventing evaporation, until the first use of the sensor. Additionally, the material from which the structure that creates the microdeposit and microchannel has been manufactured will be non-permeable to the reference solution.
• the structure that creates the microdeposit is at least partially of a gas permeable polymer, such as polydimethylsiloxane, which allows the sensor to be stored dry and can be used after a few hours of soaking.
• a gas permeable polymer such as polydimethylsiloxane
• This advantage is important to facilitate the storage and commercialization of the sensor or to facilitate its transport in case it is used in portable measuring equipment.
• a second object of the present invention is the method of manufacturing the ion measurement sensor based on differential measurement described above. Said method at least comprises the following phases:
• the second weld material wafer has at least one hole in proximity to each microdeposit, so that each hole during the phase Welding is placed in correspondence with the door of a second field effect transistor leaving said door of the second transistor exposed to the outside so that it is in contact with the solution to be measured.
• the coupling phase of the structure on the first wafer comprises adding a plurality of layers of weldable material previously subjected to a photolithography process on the first wafer, to generate the structure with the microdeposit and microchannels.
• the coupling phase of the structure on the first wafer comprises previously subjecting the weldable material structure to a recessing process for the creation of microdeposits and microchannels.
• This process of cajeado can be by emptying, molding, extrusion or similar of a second wafer.
• the microchannel is integrated into the chip by means of a longitudinal recess in the surface of the first wafer, that is, of the chip.
• the structure of the REFET is completed by welding a second wafer that already only contains the deposits, or by adding layers of weldable and photolithographic material on the ISFETs, to form the walls of the microdeposit and the caps of said microdeposits It is planned to deposit a layer of insulating material on the surface of the first and second field effect transistors to isolate the drain and the source of the first and second field effect transistors and the solution substrate.
• some wafer structure can be used that provides the insulation so that said transistors are also electrically isolated from the substrate without the need to use encapsulating material at their edges.
• SOI wafers thin semiconductor layer on an insulating layer
• a trench must be made in the surrounding semiconductor layer. totally each of the transistors, then deposit the insulating layer, and finally remove the insulating layer from the transistors door and wire welding areas (connection pads).
• Another way to obtain isolation is to form the transistors within a semiconductor region isolated from the rest of the substrate by means of a pn junction.
• a third object of the present invention is a conditioning vessel for preserving the sensor described above between measures that allows the sensor to last indefinitely.
• the conditioning vessel will be filled with the reference solution, which allows the solution contained in said microdeposit to be renewed by diffusion through the microchannel.
• a transient voltage suppressor to protect the transistors from electrostatic discharges for example connected between the electrode and the transistor substrate terminal
• a thermistor to measure temperature and compensate for the thermal drift of the sensor
• 3 a memory for storing sensor parameters, for example the ion sensitivity and the coefficients of variation with the temperature of each sensor
• 6) a microcontroller 7) a display to show the measurement data
• a serial protocol for example the USB standard
• an electronic device for example a computer or a mobile phone smart
• 8) a battery 9) a communications circuit and an antenna to communicate data wirelessly to other electronic equipment.
• RFID type ion sensor Radio Frequency Identification
• the ISFET and REFET would be integrated with a measuring circuit and an analog-digital converter and with the rest of the circuitry and components typical of an RFID tag. This would allow an RFID tag reader to be used to obtain the ion measurement data from the outside of a closed container, the RFID sensor being immersed in the liquid to be measured inside the container.
• FIGURES Figure 1. Shows a sectional view of a particular embodiment of the ion sensor based on differential measurement object of the present invention.
• Figure 2. Shows a sectional view of the particular embodiment of the ion sensor shown in Figure 1 to which a microchannel and microdeposition sealing means has been added.
• Figure 3.- Shows a particular embodiment of the method of manufacturing the ion sensor based on differential measurement, object of the present invention.
• Figure 3a shows the alignment phase of both wafers.
• Figure 3b shows the welding phase of Both wafers.
• Figure 3c shows the phase of filling the tanks with solution or hydrogel.
• the 3d figure shows the cutting phase of the resulting wafer in chips.
• Figure 4.- Shows a particular embodiment of an alternative method of manufacturing the ion sensor based on differential measurement, object of the present invention.
• Figure 4a shows the ISFET.
• Figures 4b to 4g show the subsequent welding phases of polymer layers alternated with photolithography phases to configure the microdeposition and the microchannel.
• Figure 5a shows a plan view of an embodiment of the sensor with all its components.
• Figure 5b shows the sensor of Figure 5a in which the encapsulating polymer has been added.
• Figure 6. Shows an example of the use of the ion sensor of Figure 1 in the measurement of a determined ion concentration of any solution.
• FIG. 1 shows an embodiment of the ion sensor based on the differential measurement, object of the present invention, for the specific case in which it was designed for the measurement of the H + ion, that is, for the case in which You want to measure the pH of a specific solution.
• Said sensor is formed by an ISFET (1) and a REFET (2), where the REFET (2) is in turn constituted by another ISFET (3) whose door (4) is kept exposed to a constant pH by incorporating a structure (5) that creates a microdeposit (6) filled with a reference solution (internal solution) with a constant pH.
• Said microdeposit (6) is connected to the outside by means of a microchannel (7).
• This microchannel in this specific embodiment comprises being formed by two sections thereof perpendicular to each other, but could be formed by a single longitudinal section or have any other configuration.
• Both the ISFET (1) and REFET (2), both integrated in two chips, are in turn fixed on a substrate (8) that has a defined metal layer in the form of connection tracks (9) and an electrode area (10)
• the chips are partially encapsulated using "chip-on-board” techniques, that is, wire-bonding connection (solder of the pads (14) of chip connection by wire (12)) and glob-top protection (encapsulating polymer (1 1)).
• the encapsulating polymer (1 1) covers the connecting wires (12) and the connecting tracks (9) and exposes the doors of the ISFET (13) and the REFET (4) of, at least partially, the structure (5) which creates the microdeposit (6) and, completely, the output of the microchannel (7) of the REFET (2), as well as the electrode area (10).
• the REFET chip (2) is constituted by the ISFET chip (3) with the structure (5) adhered to its surface forming the microdeposit (6) on the door (4) of said ISFET (3) and the microchannel (7), so that the walls and ceiling of both the microdeposit (6) and the microchannel (7) are of the material of said structure (5), while the floor is formed by the surface of the ISFET (3).
• Figure 2 shows a concrete embodiment in which sealing means of the microchannel (7) and the microdeposit (6) have been adhered to the output of the microchannel (7).
• an adhesive strip (15) having a portion without adhesive material has been adhered so that it can be easily removed by a user.
• This specific embodiment allows to extend the life of the sensor since the reference solution in the microdeposit (6) and in the microchannel (7) of the REFET (2) is completely isolated preventing leakage or evaporation of the same so far in that the sensor will be used for the first time and the adhesive strip (15) is removed.
• Figure 3 shows an exemplary embodiment of the sensor manufacturing method described herein. The method is based on the formation of the microdeposit and the microchannel and its soldier on the ISFET by means of planar technology processes, such as those used for the manufacture of microfluidic systems.
• Figure 3A shows a first wafer (16) where ISFETs, (20) and connection pads (14) and a second wafer (17) with microdeposits (18) and microchannels (previously) have been equally balanced. 19) previously made on its lower face.
• This second wafer (17) is made of a material that allows it to be welded to the first wafer (16). Both wafers (16.17) are aligned so that each ISFET (20) corresponds to a microchannel (19) and a microdeposit (18).
• the phase in which the welding between both wafers (16,17) is performed is shown in Figure 3B.
• Welding is preferably of the chemical type, that is, by means of surface functionalization with molecules that react forming covalent bonds, but other welding techniques can also be used, as long as they do not distort the geometry of the microchannels (19).
• Many combinations of materials that can be functionalized and chemically welded are known in the state of the art.
• the first wafer (16) has the surface of silicon oxide or oxynitride and the second wafer (17) is of polydimethylsiloxane (PDMS), both functionalized by means of an oxygen plasma.
• PDMS polydimethylsiloxane
• the second wafer (17) is easily manufactured with microfabrication technologies used for the implementation of microfluidic systems. It is planned to have the structure already formed by molding or some other technique.
• ISFETs (20) are manufactured with a technology that allows them to be isolated from the substrate (8). This technique is based on the use of SOI wafers and the definition of isolation trenches around ISFETs. This way the encapsulation is facilitated because it is no longer necessary to protect the chip edges. This allows chips of smaller area to be encapsulated, since the distance from the ISFET door to the edges of the chip is no longer critical because there is no danger of the door being accidentally covered when the encapsulating polymer is applied.
• Figure 4 shows another alternative technique of manufacturing REFETs, where starting from a chip where an ISFET is integrated, a REFET is obtained by adding layers.
• Figure 4a shows an ISFET on a chip (22) in which said ISFET comprises a source pad (23) connected to the source (27) of the transistor, a drain pad (25) connected to the drain (28) of the transistor and a substrate pad (24) (all of them form the connection pads (14) of the ISFET) and a door (26).
• a first polymer layer (29) is deposited by welding or a prepolymer is deposited by centrifugation and then thermo-curing, as shown in Figure 4b.
• This polymer layer (29) is structured (figure 4c) by lithography creating the microchannel (30) and the microdeposit (31) and freeing the polymer connection pads (23,24,25). Subsequently, and as shown in Figure 4d, a second layer (32) of polymer is welded by rolling onto the first layer (29) of polymer. Again, this second polymer layer (32) is structured by photolithography, increasing the volume of the microdeposit (31) and closing the microchannel (30) (figure 4e) but leaving the exit orifice (33) of the microchannel (30) free.
• a third layer (34) of polymer is welded and structured by lithography ( Figures 4f and 4g) so that the microdeposit (31) is closed and only the outlet orifice (33) of the microchannel (30) remains open.
• the three layers of polymer (29,32,34), which can be of SU8, define the microdeposit (31) and the microchannel (30) which in turn connects with the outside through its outlet orifice (33) .
• This outlet orifice (33) allows the microchannel (30) and the microdeposition (31) to be filled at the wafer level with hydrogel or with any reference solution.
• the structure of an ISFET is similar to that of a MOS transistor (diffusion of drain and source in a doped semiconductor substrate) with the difference that it does not have a door electrode and the door dielectric is exposed.
• MOS transistor diffusion of drain and source in a doped semiconductor substrate
• the ISFET and REFET devices must have the door dielectric in contact with the solution, the ISFET door dielectric with the solution to be measured and the REFET door dielectric with the reference solution, but they must have the drain, the source and the substrate isolated from the respective solutions.
• a layer of insulating material is deposited on the surface of the chips during manufacture (at the wafer level), and the edges of the chip during the process are protected with the encapsulating polymer of encapsulation.
• a manufacturing technology that allows electrically insulating the substrate of the device from the edges of the chip can be used, so that it is not necessary to protect them with polymer, for example using SOI wafers (Silicon on insulator).
• SOI wafers Silicon on insulator
• the two ways of insulating the substrate can be used, but the first requires a large space ( ⁇ 2mm) between the ISFET door and the edge of the chip in all the directions, forcing large chips, and therefore expensive.
• the second option through the use of SOI wafers, is made more suitable for the manufacture of the ISFET-REFET sensor described here, since it allows the encapsulation of small area chips, requiring only that the separation be large in one direction (for example , in a rectangular chip the ISFET door would be located at one end of the chip and the connection pads to be protected with glob-top at the other end of the chip).
• An interesting variant of the REFET is the one with the microdeposit and the microchannel filled with a hydrogel.
• the advantages in this case are the avoidance of bubble formation problems in the microchannel and the microdeposit (which could cause a malfunction) and the possibility of storing the sensor dry until it is used.
• the hydrogel would be soaked in reference solution and would do the same function as the internal solution without hydrogel. This material is very hygroscopic, so it would take much longer to dry if the sensor is left out of the solution. If it dries completely, it can be easily rehydrated by re-immersing it in distilled water or in reference solution without danger of bubbles forming.
• Figure 5 shows a plan view of an exemplary embodiment of a pH sensor according to the present invention.
• Figure 5a shows a PCB substrate (35) in which an ISFET and a REFET have been fixed as described in Figure 4, an electrode (36) and connection tracks (37). These tracks are connected to both the ISFET and the REFET via the connection pads (23,24,25) by welding with wires (38).
• Figure 5b shows the sensor of Figure 5a in which the encapsulating material (39) that partially covers both the ISFET and the REFET has been deposited and totally to the connections thereof with the connection tracks (37).
• Another object of the invention is also an ion measurement method by means of a described ISFET / REFET sensor. While not being used, the sensor (40) is inserted into a conditioning vessel (41) filled with a reference solution (42) ( Figure 6a). This reference solution (42) also serves as a calibration solution as its known ion concentration.
• the sensor (40) Once the sensor (40) has been introduced into the reference solution (42) for the first time and sufficient time has been allowed for the microdeposit (6) to fill or soak up said solution (42), said sensor (40 ) is removed from the conditioning vessel (41), rinsed, and immersed in the solution to be measured (43) located within a measuring vessel (44), keeping the micro-reservoir (6) of the REFET filled with the reference solution (42) ( Figure 6b). After use, the sensor (40) is cleaned and reinserted into the conditioning vessel (41) so that the solution of the microdeposit (6) is equilibrated with the solution of the vessel and returns to its original ion concentration.
• the sensor (40) will function properly as long as the usage time is less than the time the sensor (40) is immersed in the reference solution (42) inside the conditioning vessel. What brings the present invention to the forefront is that the sensor (40) is kept in the conditioning vessel (41) between one measure and the next, which means that the sensor does not have a limited lifetime due to contamination of the reference or diffusion solution of its components abroad.
• An added advantage is that since the conditioning vessel (41) is filled with the reference solution (42), whose ion concentration is fixed (for example, a buffered solution to maintain the constant pH in the event that the ISFET is selective at pH and the REFET is constructed with a pH selective ISFET), the sensor can be calibrated before being removed from it transparently to the user.
• the ion sensor object of the present invention is to integrate the sensor into a self-diagnostic medical device by measuring, for example, urine ions, which may be of interest for the control of diseases such as lithiasis and osteoporosis.
• Another possible application would be the measurement of vaginal pH for birth control, where the measurement made by the sensor was transmitted to a mobile device (for them the sensor object of the present invention must have an interface for communication with the mobile device) .
• Another possible application for the sensor would be ion monitoring in cell cultures. By introducing the sensor into the culture medium, the condition of the cells could be continuously monitored without opening the container lid. In this case, the measurement could be transmitted through a wireless communications system integrated in the sensor itself.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Microelectronics & Electronic Packaging (AREA)
• Physics & Mathematics (AREA)
• General Physics & Mathematics (AREA)
• Biochemistry (AREA)
• Electrochemistry (AREA)
• Analytical Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Health & Medical Sciences (AREA)
• Molecular Biology (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Computer Hardware Design (AREA)
• Condensed Matter Physics & Semiconductors (AREA)
• Power Engineering (AREA)
• Manufacturing & Machinery (AREA)
• Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)

Priority Applications (10)

Applications Claiming Priority (2)

Related Child Applications (2)

Publications (1)

Family

ID=52633296

Family Applications (1)

Country Status (9)

Cited By (1)

Families Citing this family (10)

Citations (2)

Family Cites Families (22)

• 2014
  • 2014-02-11 ES ES201430180A patent/ES2542927R1/es active Granted
• 2015
  • 2015-01-29 JP JP2016550810A patent/JP2017505443A/ja active Pending
  • 2015-01-29 US US15/113,381 patent/US10067085B2/en active Active
  • 2015-01-29 WO PCT/ES2015/070063 patent/WO2015121516A1/es not_active Ceased
  • 2015-01-29 CN CN201580007758.0A patent/CN106104265A/zh active Pending
  • 2015-01-29 CA CA2938155A patent/CA2938155A1/en not_active Abandoned
  • 2015-01-29 EP EP15708848.5A patent/EP3106865B1/en active Active
  • 2015-01-29 KR KR1020167021498A patent/KR20160119096A/ko not_active Withdrawn
  • 2015-01-29 MX MX2016010017A patent/MX2016010017A/es unknown
  • 2015-01-29 ES ES15708848T patent/ES2818111T3/es active Active
• 2018
  • 2018-06-28 US US16/021,926 patent/US10436743B2/en active Active
• 2019
  • 2019-08-02 US US16/530,574 patent/US11029278B2/en active Active

Patent Citations (2)

Non-Patent Citations (7)

Also Published As

Similar Documents

Legal Events