EP1238269A2 - Capteur potentiometrique - Google Patents

Capteur potentiometrique

Info

Publication number
EP1238269A2
EP1238269A2 EP00985509A EP00985509A EP1238269A2 EP 1238269 A2 EP1238269 A2 EP 1238269A2 EP 00985509 A EP00985509 A EP 00985509A EP 00985509 A EP00985509 A EP 00985509A EP 1238269 A2 EP1238269 A2 EP 1238269A2
Authority
EP
European Patent Office
Prior art keywords
flow channel
ion
sample solution
potentiometric sensor
analyte ions
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00985509A
Other languages
German (de)
English (en)
Inventor
Andreas Manz
Ratna Tantra
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Imperial College of Science Technology and Medicine
Original Assignee
Imperial College of Science Technology and Medicine
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Imperial College of Science Technology and Medicine filed Critical Imperial College of Science Technology and Medicine
Publication of EP1238269A2 publication Critical patent/EP1238269A2/fr
Withdrawn legal-status Critical Current

Links

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
    • G01N27/4035—Combination of a single ion-sensing electrode and a single reference electrode
    • 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
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
    • G01N27/4473—Arrangements for investigating the separated zones, e.g. localising zones by electric means

Definitions

  • the present invention relates to a microfabricated chip-based potentiometric sensor which includes at least one ion-selective membrane electrode, and a measurement system incorporating the same.
  • Ion-selective membrane electrodes are electrochemical electrodes that can be used in the direct measurement of the activity, and hence concentration, of analyte ions in sample solutions, particularly complex organic solutions. Selectivity for one species over another is determined by the nature and chemical composition of the ion-selective membrane and the associated reaction layers used to fabricate the electrode. Such ion- selective membranes serve as an additional component of a classic two-electrode galvanic cell, with the potential developed at the interface between the membrane and the sample solution being directly or indirectly related to the activity of the analyte ions in the sample solution.
  • the measurement principle of electrochemical cells incorporating ion-selective membrane electrodes is quite simple. Two electrodes are separated by an ion-selective membrane, with the solution on one side of the membrane being an internal reference solution of known composition and including ions to which one electrode, referred to as the internal electrode, and the membrane respond, and the solution on the other side of the membrane being a sample solution in contact with the other electrode, referred to as the external reference electrode.
  • the phase-boundary potentials will be constant except for the membrane potential which is the difference in the electrical potential between the internal reference solution and the sample solution; the variation in this membrane potential being an indication of the activity of the analyte ions in the sample solution.
  • the internal electrode, the internal reference solution and the ion-selective membrane are often housed in a single unit to provide an ion-selective electrode.
  • the voltage is measured as an electromotive force (EMF) between the ion-selective electrode (ISE) and the reference electrode (RE) according to the formula
  • Ion-selective microelectrodes for measuring ionic activity have been in existence for some time as discussed in the review article by Thomas B ⁇ hrer et al entitled '"Neutral- Carrier-Based Ion-Selective Microelectrodes Design and Application A Review” as published in Analytical Sciences. December 1998, Vol. 4, pages 547 to 557.
  • Coated wire electrodes comprise a conductive element, typically a metal wire, coated with a polymeric ion-selective membrane, and provide very small, durable ion- selective electrodes.
  • ISFETs solid-state field effect transistor
  • CHEMFETs solid-state field effect transistor
  • the principle of operation of these ISFETs or CHEMFETs is that the outer membrane phase-boundary potential determines the voltage at the gate of the field effect transistor, and, when the field effect transistor is a current-measuring circuit, the resulting current should be indicative of the membrane potential and hence the activity of the analyte ions in the sample solution.
  • the most significant problem associated with these devices is the same problem associated with coated wire electrodes, namely, that of drift arising as a result of changes in the coupling between the gate of the field effect transistor and the ion-selective membrane.
  • the coupling is influenced by certain species diffusing through the ion-selective membrane to the interface with the gate of the field effect transistor.
  • Microfabricated potentiometric sensors have also been developed in silicon wafers, as disclosed in a paper by Uhlig et al entitled "Miniaturized Ion-Selective Chip Electrode for Sensor Application” as published in Analytical Chemistry, Vol. 69, No. 19, pages 4032 to 4038. These miniaturised sensors are fabricated by depositing a polymeric ion-selective membrane into anisotropically etched wells in a silicon wafer, and, in use, a sample solution is brought into contact with one side of the silicon wafer.
  • potentiometric sensors are all of scientific interest, these sensors require a significant equilibration time as the diffusion flux of the analyte ions in the hydrostatic sample solutions used by the s nsors is relatively low. It is thus an aim of the present invention to provide a microfabricated chip-based potentiometric sensor which is robust and provides for analyte ions in sample solutions to be driven relative to an ion-selective membrane and thereby allow rapid measurement. In this way, the potentiometric sensor of the present invention provides means for performing on-line measurements, preferably continuously.
  • the present invention provides a microfabricated potentiometric sensor, comprising: a substrate chip; a flow channel defined by the substrate chip through which analyte ions of a sample solution are in use driven; at least one ion-selective electrode comprising a chamber defined by the substrate chip and including a port in communication with the flow channel, an ion-selective membrane disposed in the chamber, and a conductive element configured such as in use to be in electrical connection with the ion-selective membrane; a reference electrode configured such as in use to be in electrical connection with the flow channel; whereby, on driving analyte ions of a sample solution through the flow channel, an electromotive force is developed between the at least one ion-selective electrode and the reference electrode which is representative of the activity of the analyte ions.
  • this sensor in requiring the analyte ions of a sample solution to be driven through a flow channel, provides a sufficient diffusion flux of the analyte ions, as compared to the ionic diffusion flux in a hydrostatic sample solution, that the activity of the analyte ions can be rapidly measured.
  • the ion-selective membrane includes one or both of an appropriate lipophilic ionophore or an ion exchanger as the ion-transfer agent.
  • the chamber is filled completely by the ion-selective membrane.
  • the chamber is filled partially by the ion-selective membrane.
  • the chamber comprises a first region, and at least one second, junction region of smaller dimension than the first region in communication with the flow channel.
  • the chamber comprises a plurality of junction regions, each being in communication with respective ones of spaced locations in the flow channel.
  • junction regions are in communication with locations spaced along the length of the flow channel.
  • the at least one ion-selective electrode further comprises a reference solution, with the conductive element being disposed in the reference solution such as to be in electrical connection with the ion-selective membrane through the reference solution.
  • the senor comprises a plurality of ion-selective electrodes, with the ports of the chambers of the ion-selective electrodes being in communication with respective ones of spaced locations in the flow channel.
  • the ports of the chambers of the ion-selective electrodes are in communication with locations spaced along the length of the flow channel.
  • the reference electrode comprises a further chamber defined by the substrate chip and including a port in communication with the flow channel, a conductive material disposed in the further chamber, and a further conductive element configured such as in use to be in electrical connection with the conductive material.
  • the further chamber is filled completely by the conductive material.
  • the chamber is filled partially by the conductive material.
  • the further chamber comprises a first region, and at least one second, junction region of smaller dimension than the first region in communication with the flow channel.
  • the reference electrode further comprises a further reference solution, with the further conductive element being disposed in the further reference solution such as to be in electrical connection with the conductive material through the further reference solution.
  • the flow channel includes inlet and outlet ports through which a liquid flow of the sample solution is in use driven.
  • the senor is configured such that analyte ions are electrically driven through the flow channel.
  • the flow channel includes an inlet port through which a volume of a sample solution is in use introduced thereinto, and the sensor further comprises first and second conductive elements disposed such as to generate a potential gradient along the flow channel when a d.c. high voltage is applied thereacross.
  • the present invention also extends to a measurement system for measuring the activity of analyte ions in a sample solution which incorporates the above-described potentiometric sensor.
  • a measurement system for measuring the activity of analyte ions in a sample solution which incorporates the above-described potentiometric sensor.
  • Such measurement systems would find application in the clinical and environmental fields.
  • the present invention also provides a method of measuring the activity of analyte ions in a sample solution, comprising the steps of: providing a potentiometric sensor comprising a substrate chip defining a flow channel, at least one ion-selective electrode in communication with the flow channel, and a reference electrode in communication with the flow channel; driving analyte ions of a sample solution through the flow channel; and measuring the electromotive force developed between the at least one ion-selective electrode and the reference electrode so as to determine the activity of the analyte ions.
  • the sample solution is fed as a liquid flow through the flow channel.
  • the sample solution is fed through the flow channel at a flow rate of from 1 pl/s to 1 ml/s.
  • analyte ions are electrically driven by electrohvdrodvnamic or electroosmotic flow along the flow channel.
  • a volume of a sample solution is introduced into the flow channel prior to applying the driving voltage.
  • Figure 1 schematically illustrates in perspective view a chip-based potentiometric sensor in accordance with a first embodiment of the present invention
  • Figure 2 illustrates the chip layout of the sensor of Figure 1
  • Figure 3 illustrates a first modified chip layout of the sensor of Figure 1 ;
  • Figure 4 illustrates a second modified chip layout of the sensor of Figure 1 ;
  • Figure 5 illustrates schematically a sectional view of the ion-selective electrode of the sensor of Figure 1 ;
  • Figure 6 illustrates schematically a sectional view of the sample solution reservoir and the reference electrode of the sensor of Figure 1 :
  • Figure 7 illustrates schematically a sectional view of the inlet configuration of the flow channel of the sensor of Figure 1;
  • Figure 8 schematically illustrates in perspective view a measurement system incorporating the sensor of Figure 1 ;
  • Figure 9 illustrates a plot of electromotive force as a function of the log of concentration for a sample solution measured using the sensor of Figure 1 ;
  • Figure 10 illustrates the chip layout of a chip-based potentiometric sensor in accordance with a second embodiment of the present invention
  • Figure 1 1 illustrates the chip layout of a chip-based potentiometric sensor in accordance with a third embodiment of the present invention
  • Figure 12 illustrates the chip layout of a chip-based potentiometric sensor in accordance with a fourth embodiment of the present invention
  • Figure 13 schematically illustrates in perspective view a chip-based potentiometric sensor in accordance with a fifth embodiment of the present invention
  • Figure 14 illustrates the chip layout of the sensor of Figure 13
  • Figure 15 illustrates schematically a sectional view of the ion-selective electrode of the sensor of Figure 13;
  • Figure 16 illustrates schematically a sectional view of the reference electrode of the sensor of Figure 13
  • Figure 17 illustrates schematically a sectional view of the third to seventh tubular sections and associated electrode elements of the sensor of Figure 13;
  • Figure 18 schematically illustrates in perspective view a measurement system incorporating the sensor of Figure 13;
  • Figure 19 illustrates the chip layout of a chip-based potentiometric sensor in accordance with a sixth embodiment of the present invention.
  • Figure 1 illustrates a microfabricated potentiometric sensor 1 in accordance with a first embodiment of the present invention as fabricated in a substrate chip 2.
  • the chip 2 includes flow channel 3, in this embodiment of linear section, which includes an inlet port 5 and an outlet port 7 through which a sample solution is in use fed.
  • the flow channel 3 is 10 mm in length. 200 ⁇ m in width and 20 ⁇ m in depth.
  • the chip 2 further includes a chamber 9 which contains an ion-selective membrane 1 1.
  • the chamber 9 comprises a first, main region 13, in this embodiment of flattened U- shaped section, which includes first and second ports 15, 17 and a second, narrow junction region 19 which is in fluid communication with the flow channel 3 and extends substantially between midpoints of the main region 13 and the flow channel 3.
  • the main region 13 is 12 mm in length, 200 ⁇ m in width and 20 ⁇ m in depth
  • the first and second ports 15, 17 are 800 ⁇ m in diameter
  • the junction region 19 is 830 ⁇ m in length, 20 ⁇ m in width and 20 ⁇ m in depth.
  • the chamber 9 is filled completely with the ion-selective membrane 11.
  • the chamber 9 can be partially filled with ion-selective membrane 11.
  • the ion-selective membrane 1 1 fills only the junction region 19 and the web of the U-shaped main region 13 of the chamber 9. In the modification of Figure 4, the ion-selective membrane 1 1 fills only the junction region 19 of the chamber 9.
  • the chamber 9 can include an inert, porous supporting material, such as a ceramic, which is provided to support the ion-selective membrane 1 1 and improve the mechanical stability thereof.
  • an inert, porous supporting material such as a ceramic
  • the chip 2 is fabricated from two plates, in this embodiment composed of microsheet glass.
  • the plates could be formed of silicon wafers.
  • a first step one of the plates is etched by HF wet etching to form wells which define the flow channel 3 and the main and junction regions 13, 19 of the chamber 9, with the wells having the respective dimensions mentioned hereinabove.
  • a second step four holes are drilled, in this embodiment by ultrasonic abrasion, into the other plate so as to provide the inlet and outlet ports 5, 7 of the flow channel 3 and the first and second ports 15, 17 of the chamber 9.
  • the two plates are bonded together by direct fusion bonding.
  • the chamber 9 is filled with an organic cocktail which provides the ion-selective membrane 1 1.
  • Filling is achieved by maintaining a gas flow, typically of an inert gas such as argon, through the flow channel 3 and introducing a predetermined volume of the organic cocktail into one of the ports 15, 17 of the chamber 9.
  • a gas flow typically of an inert gas such as argon
  • the main and junction regions 13, 19 of the chamber 9 are filled with the organic cocktail; organic cocktail being prevented from entering the flow channel 3 by the gas flow maintained therethrough.
  • this material is introduced prior to or after fusing together the two plates.
  • the chip 2 is allowed to stand until the solvent in the organic cocktail of the ion-selective membrane 11 has evaporated and a dry ion-selective membrane 11 is formed.
  • the chip 2 can be dried in a desiccator.
  • the organic cocktail comprises tetrahydrofuran (THF) as a solvent, o-nitrophenyloctyl ether (o-NOPE) as a solvent mediator, polyvinyl chloride (PVC) as a polymeric matrix material, potassium tetrakis(4-chlorophenyl)borate (TPB) as a lipophilic salt for reducing electrical resistance, and an ion-transfer agent.
  • THF tetrahydrofuran
  • o-NOPE o-nitrophenyloctyl ether
  • PVC polyvinyl chloride
  • TPB potassium tetrakis(4-chlorophenyl)borate
  • ion-transfer agent ion-transfer agent.
  • suitable polymeric matrix materials include fluorosilicone elastomers which have a relatively low resistance and high dielectric constant.
  • the chamber 9 can be surface treated so as to be of increased hydrophobicity.
  • the chamber 9 is silanized by treating with a silane solution.
  • silane solutions include the siloxane based solution RepelcoteTM and 5 % dimethylchlorosilane in carbon tetrachloride.
  • the chamber 9 is treated after bonding together the two plates by feeding a metered volume of silane solution, typically using a syringe needle, into one of the ports 15, 17 of the chamber 9 and simultaneously applying a vacuum, typically using a vacuum pump, to the other of the ports 15, 17 of the chamber 9 so as to fill the same.
  • a gas flow typically an inert gas such as argon, is maintained in the flow channel 3.
  • the silane solution is maintained in the chamber 9 for a short time, typically from 2 to 3 minutes, and then completely withdrawn using the vacuum pump. This process is then repeated so as to ensure complete silanization of the chamber 9.
  • the sensor 1 further comprises a first tubular section 21, one of the ends of which is enlarged and bonded to the chip 2, in this embodiment by an epoxy resin, so as to overlie the first port 15 of the chamber 9; the first tubular section 21 defining a reservoir which contains an internal reference solution 23, in this embodiment 0.1 M of KC1.
  • the sensor 1 further comprises an electrode element 25, in this embodiment an Ag/AgCl wire, disposed in the reference solution 23 contained by the first tubular section 21.
  • the sensor 1 further comprises a second tubular section 27. one of the ends of which is enlarged and bonded to the chip 2, in this embodiment by an epoxy resin, so as to overlie the outlet port 7 of the flow channel 3; the second tubular section 27 defining a reservoir for containing the sample solution fed through the flow channel 3.
  • the sensor 1 further comprises a reference electrode 29 disposed in the second tubular section 27 so as to contact the sample solution when contained therein.
  • the reference electrode 29 comprises a Flexref r I minaturized Ag/AgCl electrode as available from World Precision Instruments of Stevenase. UK.
  • the sensor 1 further comprises a third tubular section 3 1. in this embodiment a fused silica capillary tube, bonded to the chip 2, in this embodiment by an epoxy resin, so as to overlie the inlet port 5 of the flow channel 3.
  • the ion-selective membrane 1 1, the reference solution 23 and the electrode element 25 together define an ion-selective electrode, such that, on feeding a sample solution through the flow channel 3, a potential is developed across the ion-selective electrode and the reference electrode 29 corresponding to the membrane potential which is the electrical potential between the reference solution 23 and the sample solution and is representative of the activity of the analyte ions in the sample solution.
  • Figure 8 illustrates a measurement system incorporating the above-described potentiometric sensor 1.
  • the measurement system comprises first and second solution feeders 33, 35, in this embodiment syringe pumps, and a valve switch 36, with the solution feeders 33, 35 being connected by tubing 37, 39 to the inlets of the valve switch 36 and by tubing 43 to the third tubular section 31 at the inlet port 5 of the flow channel 3.
  • the concentration of the sample solution fed to the flow channel 3 can be altered without any interruption to the flow and hence measurement cycle.
  • the measurement system further comprises a pump 45, in this embodiment a peristaltic pump, connected by tubing 47 to the sample solution reservoir defined by the second tubular section 27 for feeding the measured solution to waste.
  • a pump 45 in this embodiment a peristaltic pump, connected by tubing 47 to the sample solution reservoir defined by the second tubular section 27 for feeding the measured solution to waste.
  • the measurement system further comprises a data acquisition unit 49 for logging the electromotive force developed across the ion-selective electrode and the reference electrode 29 of the sensor 1.
  • the data acquisition unit 49 comprises a PICO-LOG ' data acquisition system as available from Pico-Technology of Cambridge. UK connected to the ion-selectiv e electrode and the reference electrode 29 through a buffer amplifier for converting the high impedance voltage to a low impedance voltage.
  • the solution feeders 33, 35 and the valve switch 36 are configured to feed a sample solution having known concentration at a predetermined flow rate through the flow channel 3 of the sensor 1.
  • the electromotive force generated across the ion-selective electrode and the reference electrode 29 is logged by the data acquisition unit 49, which data can be used to provide an on-line measurement of the activity of the analyte ions in the sample solution.
  • a potentiometric sensor 1 as described hereinabove was fabricated for measuring the concentration of BaCl 2 in water.
  • the ion-selective membrane 1 1 was formed from an organic solution comprising 1 mL of o-NOPE, 70 mg of PVC, 2 mg of TPB salt. 7 mg of Ba" + Vogtle ionophore and 0.5 ml of THF.
  • the electromotive force was measured at various concentrations (c) of BaCl 2 in water at a flow rate of 1/60 ⁇ l/s and intervals of 5 seconds.
  • FIG 10 illustrates the chip layout of a chip 2 of a potentiometric sensor 1 in accordance with a second embodiment of the present invention.
  • This chip 2 is substantially identical to that of the above-described first embodiment, and thus in order to avoid unnecessary duplication of description only the differences will be described in detail, with like parts being designated by like reference signs.
  • This chip 2 is substantially identical to that of the above-described first embodiment, and thus in order to avoid unnecessary duplication of description only the differences will be described in detail, with like parts being designated by like reference signs.
  • the chamber 9 includes a plurality of junction regions 19a-g, each being in fluid communication with respective ones of locations spaced along the length of the flow channel 3.
  • the electromotive force developed between the ion-selective electrode and the reference electrode 29 is a signal average representing the bulk activity of the analyte ions in the volume of the sample solution bounded by the upstreammost and downstreammost junction regions 19a, 19g.
  • FIG. 1 1 illustrates the chip layout of a chip 2 of a potentiometric sensor 1 in accordance with a third embodiment of the present invention.
  • This chip 2 is quite similar to that of the above-described first embodiment, and thus in order to avoid unnecessary duplication of description only the differences will be described in detail, with like parts being designated by like reference signs.
  • This chip 2 differs from that of the first-described embodiment in including a plurality of chambers 9. the junction regions 19 of which are in fluid communication with respective ones of locations spaced along the length of the flow channel 3, and with each of the first ports 15 of the chambers 9 including an associated first tubular section 21 and electrode element 25 such as to define a plurality of ion-selective electrodes.
  • FIG. 12 illustrates the chip layout of a chip 2 of a potentiometric sensor 1 in accordance with a fourth embodiment of the present invention.
  • This chip 2 is quite similar to that of the above-described third embodiment, and thus, in order to avoid unnecessary duplication of description, only the differences will be described in detail, with like parts being designated by like reference signs.
  • This chip 2 differs from that of the third-described embodiment only in that the main regions 13 of the chambers 9 are of linear section and include only a single port 15.
  • an integrated multi-analyte sensor is provided.
  • Figure 13 illustrates a microfabricated potentiometric sensor 101 in accordance with a fifth embodiment of the present invention as fabricated in a substrate chip 102.
  • the chip 102 includes a first, separation channel 103, in this embodiment L-shaped in section, which includes first and second ports 105, 107 and through which the analyte ions of a sample solution are in use driven.
  • the separation channel 103 has a width of 50 ⁇ m and a depth of 10 ⁇ m.
  • the chip 102 further includes a second, delivery chiinnel 109, in this embodiment of linear section, which intersects the separation cha. nel 103 and includes first and second ports 1 1 1, 1 13. through which delivery channel 109 a sample solution is in use introduced into the separation channel 103.
  • the delivery channel 109 has a width of 50 ⁇ m and a depth of 10 ⁇ m.
  • the chip 102 further includes a third, spur channel 1 14. in this embodiment of linear section, which is in fluid communication with the knee of the separation channel 103 and includes a port 1 15.
  • the chip 102 further includes a first chamber 1 16 which contains an ion-selective membrane 1 17 and is of the same construction as the chamber 9 of the above-described first embodiment.
  • the first chamber 1 16 comprises a first, main region 1 19. in this embodiment of flattened U-shaped section, which includes first and second ports 1 1. 123, and a second, narrow junction region 125 which is in fluid communication with the separation channel 103 and extends between the knee thereof and substantially the midpoint of the main region 1 19 of the first chamber 1 16.
  • the chip 102 further includes a second chamber 127 which contains a conductive material 128, in this embodiment a conductive polymeric membrane.
  • the second chamber 127 comprises a first, main region 129, in this embodiment of flattened U- shaped section, which includes first and second ports 131, 133 and a second, narrow junction region 135 which is in fluid communication with the spur channel 1 14.
  • the main region 129 is 12 mm in length, 200 ⁇ m in width and 20 ⁇ m in depth
  • the first and second ports 131, 133 are 800 ⁇ m in diameter
  • the junction region 135 is 830 ⁇ m in length, 20 ⁇ m in width and 20 ⁇ m in depth.
  • the second chamber 127 is filled completely with conductive material 128.
  • the second chamber 127 can be partially filled with conductive material 128.
  • the conductive material 128 fills only the junction region 135 and the web of the U-shaped main region 129 of the second chamber 127.
  • the conductive material 128 fills only the junction region 135 of the second chamber 127.
  • the chip 102 as with that of the above-described first embodiment, is fabricated from two plates.
  • the plates are composed of microsheet glass, but in an alternative embodiment could be formed of silicon wafers.
  • a first step one of the plates is etched by HF wet etching to form wells which define the first, second and third channels 103, 109, 1 14 and the first and second chambers 1 16, 127, with the wells having the respective dimensions mentioned hereinabove.
  • nine holes are drilled, in this embodiment by ultrasonic abrasion, into the other plate so as to provide the ports 105, 107 of the first, separation channel 103, the ports 1 1 1, 1 13 of the second, delivery channel 109.
  • the two plates are bonded together by direct fusion bonding.
  • the first chamber 1 16 is filled with an organic cocktail which provides the ion- selective membrane 1 17 in the same manner as the chamber 9 of the first-described embodiment.
  • the second chamber 127 is filled with a polymeric solution, which provides the conductive material 128. in the same manner as the first chamber 1 16 is filled with the organic cocktail.
  • the chip 102 is allowed to stand until the solvents in the organic cocktail of the ion-selective membrane 1 17 and the polymeric solution of the conductive material 128 have evaporated and the ion-selective membrane 1 17 and conductive material 128 are formed.
  • the chip 102 is dried in a desiccator.
  • the first and second chambers 116, 127 can be surface treated so as to be of increased hydrophobicity.
  • the organic cocktail comprises tetrahydrofuran (THF) as a solvent, o-nitrophenyloctyl ether (o- NOPE) as a solvent mediator, polyvinyl chloride (PVC) as a polymeric matrix material, potassium tetrakis(4-chlorophenyl)borate (TPB) as a lipophilic salt for reducing electrical resistance, and an ion-transfer agent.
  • the sensor 101 further comprises a first tubular section 137, one of the ends of which is enlarged and bonded to the chip 102. in this embodiment by an epoxy resin, so as to overlie the first port 121 of the first chamber 1 16: the first tubular section 137 defining a reservoir which contains an internal reference solution 139, in this embodiment 0.1 M of KCl.
  • the sensor 101 further comprises a first electrode element 140.
  • a first electrode element 140 in this embodiment an Ag/AgCl wire, disposed in the internal reference solution 139 contained by the first tubular section 137.
  • the sensor 101 further comprises a second tubular section 141. one of the ends of which is enlarged and bonded to the chip 102. in this embodiment by an epoxy resin, so as to overlie one of the ports 133 of the second chamber 127; the second tubular section 141 defining a reservoir for containing an external reference solution 143, in this embodiment 0.1 M KC1.
  • the sensor 101 further comprises a second electrode element 145, in this embodiment an Ag/AgCl wire, disposed in the external reference solution 143 contained by the second tubular section 141.
  • the sensor 101 further comprises a third tubular section 147, one of the ends of which is bonded to the chip 102. in this embodiment by an epoxy resin, so as to overlie the first port 105 of the separation channel 103 and define a reservoir, and a third electrode element 149 disposed in the reservoir defined by the third tubular section 147.
  • the sensor 101 further comprises a fourth tubular section 151 , one of the ends of which is bonded to the chip 102, in this embodiment by an epoxy resin, so as to overlie the second port 107 of the separation channel 103 and define a reservoir, and a fourth electrode element 153 disposed in the reservoir defined by the fourth tubular section 151.
  • the sensor 101 further comprises a fifth tubular section 155, one of the ends of which is bonded to the chip 102, in this embodiment by an epoxy resin, so as to overlie the first port 1 1 1 of the delivery channel 109 and define a reservoir, and a fifth electrode element 157 disposed in the reservoir defined by the fifth tubular section 155.
  • the sensor 101 further comprises a sixth tubular section 159, one of the ends of which is bonded to the chip 102, in this embodiment by an epoxy resin, so as to overlie the second port 1 13 of the separation channel 109 and define a reservoir, and a sixth electrode element 161 disposed in the reservoir defined by the sixth tubular section 159.
  • the sensor 101 further comprises a seventh tubular section 163, one of the ends of which is bonded to the chip 102, in this embodiment by an epoxy resin, so as to overlie the port 115 of the spur channel 1 14 and define a reservoir, and a seventh electrode element 165 disposed in the reservoir defined by the seventh tubular section 163.
  • FIG 18 illustrates a measurement system incorporating the above-described potentiometric sensor 101.
  • the measurement system comprises a data acquisition unit 167 for logging the electromotive force developed across the ion-selective electrode and the reference electrode of the sensor 101.
  • the data acquisition unit 167 comprises a PICO-LOGTM data acquisition system connected to the ion-selective electrode and the reference electrode through a buffer amplifier for converting the high impedance voltage to a low impedance voltage.
  • the measurement system further comprises a d.c. high voltage supply 169 connected to the third to seventh conductive elements 149, 153. 157 161. 165 for selectively applying a d.c. high voltage between respective ones thereof.
  • a volume of buffer solution typically about 1 ml. is introduced into the reservoirs defined by the third, fourth, fifth, sixth and seventh tubular sections 147. 151 , 155. 159. 163 and a vacuum is applied, typically using a vacuum pump, to the sixth tubular section 159 such as to fill each of the first, second and third channels 103, 109, 1 14 which together typically have a volume of about 1 ⁇ l.
  • the third tubular section 155 is emptied of the buffer solution.
  • a metered volume of a sample solution typically about 1 ml in volume, is introduced into the third tubular section 155.
  • a fourth step is used to introduce a metered volume of a sample solution into the third tubular section 155.
  • a first voltage regime is applied to the third, fifth, sixth and seventh conductive elements 149, 157, 161, 165 such as to bring a plug of the sample solution by electrokinetic injection to the intersection of the first and second channels 103, 109.
  • the voltages at the third, fifth, sixth and seventh conductive elements 149, 157, 161, 165 are 0.5 kV, 2 kV, -2 kV and 0 V respectively.
  • a second voltage regime is applied to the third, fifth, sixth and seventh conductive elements 149, 157, 161, 165 such as to cause analyte ions in the plug of the sample solution to migrate along the separation channel 103 in a direction towards the seventh electrode element 165.
  • the voltages at the third, fifth, sixth and seventh conductive elements 149, 157, 161, 165 are 3 kV, 1 kV, 1 kV and 0 V respectively.
  • the electromotive force generated across the ion-selective electrode and the reference electrode is logged by the data acquisition unit 167, which data can be used to provide an on-line measurement of the activity of the analyte ions. This measurement cycle can be repeated after flushing the chip 102 with buffer solution.
  • FIG 19 illustrates the chip layout of a chip 102 of a potentiometric sensor 101 in accordance with a sixth embodiment of the present invention.
  • This chip 102 is substantially identical to that of the above-described fifth embodiment, and thus in order to avoid unnecessary duplication of description only the differences will be described in detail, with like parts being designated by like reference signs.
  • This chip 102 is substantially identical to that of the above-described fifth embodiment, and thus in order to avoid unnecessary duplication of description only the differences will be described in detail, with like parts being designated by like reference signs.
  • junction region 135 of the second chamber 127 of the reference electrode is directly in fluid communication with the separation channel 103 at a location adjacent, but upstream of, the junction region 125 of the first chamber 1 16 of the ion-selective electrode with reference to the direction of migration of the analyte ions.
  • junction region 125 of the first chamber 1 16 of the ion-selective electrode and the junction region 135 of the second chamber 127 of the reference electrode are disposed at the same distance along the separation channel 103.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Electrochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

La présente invention concerne un capteur potentiométrique micropréfabriqué et un procédé de mesure de l"activité des ions à analyser dans une solution échantillon, le capteur comportant: une puce substrat, un canal d"écoulement délimité par la puce substrat à travers duquel les ions d"analyse de la solution échantillon sont entraînés; au moins une électrode de sélection d"ions comprenant une enceinte délimitée par la puce substrat et comportant un orifice en communication avec le canal d"écoulement, une membrane de sélection d"ions disposée dans l"enceinte, et un élément conducteur présentant une configuration telle qu"en fonctionnement il soit en liaison électrique avec la membrane de sélection d"ions ; une électrode de référence présentant une configuration telle qu"en fonctionnement elle se trouve en liaison électrique avec le canal d"écoulement; ainsi, lorsque les ions d"analyse sont entraînés à travers le canal d"écoulement, une force électromotrice se développe entre ladite au moins une électrode de sélection d"ions et l"électrode de référence qui représente l"activité des ions d"analyse.
EP00985509A 1999-12-08 2000-12-08 Capteur potentiometrique Withdrawn EP1238269A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9929069 1999-12-08
GBGB9929069.4A GB9929069D0 (en) 1999-12-08 1999-12-08 Potentiometric sensor
PCT/GB2000/004711 WO2001042774A2 (fr) 1999-12-08 2000-12-08 Capteur potentiometrique

Publications (1)

Publication Number Publication Date
EP1238269A2 true EP1238269A2 (fr) 2002-09-11

Family

ID=10865966

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00985509A Withdrawn EP1238269A2 (fr) 1999-12-08 2000-12-08 Capteur potentiometrique

Country Status (3)

Country Link
EP (1) EP1238269A2 (fr)
GB (1) GB9929069D0 (fr)
WO (1) WO2001042774A2 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE50105368D1 (de) 2001-06-28 2005-03-24 Agilent Technologies Inc Mikrofluid-System mit Regler
NL1021269C2 (nl) * 2002-08-14 2004-02-17 Lionix B V Elektrodesysteem en werkwijze voor het aanleggen van elektrische spanningen en het teweegbrengen van elektrische stromen.
DE102017109225A1 (de) * 2017-04-28 2018-10-31 Testo SE & Co. KGaA Messanordnung zum Vermessen von Flüssigkeiten

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4314755C2 (de) * 1993-05-05 1995-03-02 Meinhard Prof Dr Knoll Kapillarelektrophoretisches Trennverfahren sowie Vorrichtung zur Durchführung von chemischen oder biochemischen Analysen
DE4408352C2 (de) * 1994-03-12 1996-02-08 Meinhard Prof Dr Knoll Miniaturisierter stofferkennender Durchflußsensor sowie Verfahren zu seiner Herstellung
WO1998032008A1 (fr) * 1997-01-20 1998-07-23 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Cellule electrochimique a flux continu
AU7170298A (en) * 1997-04-30 1998-11-24 Orion Research Inc. Capillary electrophoretic separation system

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0142774A3 *

Also Published As

Publication number Publication date
WO2001042774A2 (fr) 2001-06-14
WO2001042774A3 (fr) 2001-12-27
GB9929069D0 (en) 2000-02-02

Similar Documents

Publication Publication Date Title
US6159353A (en) Capillary electrophoretic separation system
Dou et al. A dynamically modified microfluidic poly (dimethylsiloxane) chip with electrochemical detection for biological analysis
Guijt et al. Capillary electrophoresis with on‐chip four‐electrode capacitively coupled conductivity detection for application in bioanalysis
US6939451B2 (en) Microfluidic chip having integrated electrodes
Harrison et al. Towards miniaturized electrophoresis and chemical analysis systems on silicon: an alternative to chemical sensors
JP3496156B2 (ja) 流体含有構造体内における電気力を介した電気浸透力および／または電気泳動力の可変制御
US7231819B2 (en) Chemical sensor for wellbore applications
EP1097371B1 (fr) Cellule de electrochemiluminescence a electrodes de reaction sans potential electrique
Tanyanyiwa et al. Conductimetric and potentiometric detection in conventional and microchip capillary electrophoresis
US5580435A (en) System for detecting components of a sample in electrophoretic separation
US8535499B2 (en) Microfabricated liquid-junction reference electrode
Kappes et al. Electrochemical detection methods in capillary electrophoresis and applications to inorganic species
Berthold et al. Fabrication of a glass‐implemented microcapillary electrophoresis device with integrated contactless conductivity detection
JPH1010088A (ja) キャピラリ−電気泳動装置
EP3054290B1 (fr) Électrode sélective d'ions
WO2007087632A2 (fr) Cellule électrochimique microéchelle et procédés d'incorporation de cette cellule
Coltro et al. Fabrication and integration of planar electrodes for contactless conductivity detection on polyester‐toner electrophoresis microchips
Oki et al. Healthcare chip for checking health condition from analysis of trace blood collected by painless needle
Carvalho et al. A novel all-3D-printed thread-based microfluidic device with an embedded electrochemical detector: first application in environmental analysis of nitrite
US8999127B2 (en) Biological sensor measuring electrochemical and/or electrical and diamond electrode and electronic integrated circuit
US20030112013A1 (en) Potentiometric sensor
WO2001042774A2 (fr) Capteur potentiometrique
Alegret et al. Flow-through pH-ISFET+ reference-ISE as integrated detector in automated FIA determinations
US6843901B1 (en) Potential gradient detector for electrophoresis
JP4216846B2 (ja) 微小電気化学測定用電極および電気化学測定法

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20020704

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20050428

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20050907