WO2010004075A1 - Dispositivo de lectura de microarrays de tipo eléctrico y reutilizable - Google Patents
Dispositivo de lectura de microarrays de tipo eléctrico y reutilizable Download PDFInfo
- Publication number
- WO2010004075A1 WO2010004075A1 PCT/ES2009/070278 ES2009070278W WO2010004075A1 WO 2010004075 A1 WO2010004075 A1 WO 2010004075A1 ES 2009070278 W ES2009070278 W ES 2009070278W WO 2010004075 A1 WO2010004075 A1 WO 2010004075A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- reading
- microarray
- transducers
- aqueous medium
- electrical
- Prior art date
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5088—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above confining liquids at a location by surface tension, e.g. virtual wells on plates, wires
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
- B01L3/0262—Drop counters; Drop formers using touch-off at substrate or container
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/046—Function or devices integrated in the closure
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0645—Electrodes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0819—Microarrays; Biochips
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
- B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
-
- 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
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
Definitions
- the main object of the present invention is an electric microarray reading device that can be cleaned and reused more than once.
- a microarray is a set of spots or test points of small dimensions (from a few nm to a few mm) on a flat support that allows many tests to be carried out in parallel, greatly increasing the speed and the analysis capacity with respect to series analysis systems .
- Microarrays that use antibodies as a recognition element are based on different types of assay:
- Sandwich type when the analyte is captured by an antibody immobilized on the support and quantified by a second labeled antibody.
- Competitive type when copies of the analyte are immobilized in the spots of the surface of the support and the quantification of said analyte is performed indirectly from the labeled antibodies that bind to said spots in the presence of the sample to be analyzed.
- the tags can be of the optical type (fluorescent molecule, quantum dot, enzyme whose product precipitates), radioactive (radioisotopes), or electrochemical (enzyme whose product is electroactive or electroactive nanoparticles).
- optical type fluorescent molecule, quantum dot, enzyme whose product precipitates
- radioactive radioactive
- electrochemical electrochemical
- microarrays are extended more widely and can be used in the places where it is needed (next to the patient's bed in a hospital or in the primary care center), the teams must improve in terms of cost, robustness, simplicity and size.
- These analytical equipment basically consist of two distinct parts: the microarrays on which the test is performed and the device with which the reading of the result of said test is performed.
- Other accessories are also included in the system, such as a robotic arm for the deposition of recognition components or samples on the spots or measuring points of the microarray (spoter), or a device with fluidic and reactive components to perform the test automatically.
- the reading devices of electric type are the most robust, simple and of smaller size. However, they have the disadvantage of requiring a matrix of devices (electrodes or photodiodes) formed on the support itself, which forces the use of a new support and discarding the used one each time the test is performed.
- the support in addition, is a complex and expensive element, since it must include electrical transducers, etc., instead of the supports commonly used in optical systems, which simply consist of a piece of functionalized glass or plastic
- the present invention describes a device for reading microarrays of electric and reusable type that is based on the electrochemical measurement (amperometric, potentiometric or impedimetric) of the accumulation of products of an enzymatic reaction when a surface marked by enzymatic marks and a contact chemical substrate
- the novelty of this device lies in the fact that the transducers in charge of carrying out the measurement are located in a different base than the microarray support, so that the reading device can be reused for as many analyzes as desired.
- the reading device can work with the low-cost media used by the known optical systems.
- this reading device only requirement for the use of this reading device is that the enzymatic mark used, when reacting with its corresponding chemical substrate, generates a product that can be detected by the transducers, that is, a product that modifies some electrical or chemical property of the medium in which the reaction occurs.
- the transducers of the invention therefore, transform electrical or chemical quantities of a medium into electrical quantities.
- the chemical substrate In the case of impedimetric transducers, it will be necessary for the chemical substrate to be a chemical species with a net charge different from that of the sum of the net charges of the products, so that when the enzymatic reaction occurs, the concentration of charged species changes, and therefore change the conductivity of the medium.
- An example of this is the enzyme Ureasa, which reacts with urea (neutral species) produces ammonia and carbon dioxide. The ammonia is rapidly protonated giving rise to the ammonium ion (positively charged), while the carbon dioxide will partially become bicarbonate (negatively charged).
- the enzymatic reaction must produce electroactive species.
- An example is the enzyme alkaline phosphatase, which in the presence of p-aminophenyl phosphate produces p-aminophenol.
- P-aminophenol is oxidized to a potential of less than 200 mV resulting in p-quinonaimine.
- This enzyme / substrate system allows redox cycling to be used since p-quinonaimine can be reduced in turn to a potential of less than -200 mV resulting in p-aminophenol again.
- the enzymatic reaction In the case of potentiometric transducers, the enzymatic reaction must produce ions that are detectable in the transducer.
- the simplest case would be an enzyme that produces a pH change.
- a microarray is formed by a flat support, on one of whose surfaces, which we will call “test surface”, there is a matrix of spots with an enzymatic mark.
- the flat support can be any of the supports usually used with other types of reading equipment, for example optics, and can be made of materials such as glass or plastic, among others.
- an electric and reusable microarray reading device comprising the following elements:
- a base comprising support means for placing the microarray test surface parallel to a reading surface of the base.
- the support means of the base must be such that the test surface of the microarray is facing parallel to the reading surface of the base.
- the distance between both surfaces must be such that it allows a drop of an aqueous medium to simultaneously touch both surfaces, thus bringing the chemical substrate present in the aqueous medium and the enzymatic mark of the microarray spots into contact, and thus producing a chemical reaction that results in products that affect the electrical or chemical properties of the aqueous medium.
- a matrix of transducers arranged on the reading surface of the base, which translate a variation of an electrical or chemical quantity into a variation of an electrical quantity.
- the transducers are fixed to the reading surface of the base forming a matrix, so that, when the microarray is arranged on the support means, each transducer faces a spot.
- a drop of aqueous medium containing the corresponding chemical substrate must be applied between each transducer and the respective spot facing it.
- Drops of aqueous medium can be formed in any way, provided they are all of the same size, and do not touch each other.
- a micropipette or a "spoter" type equipment could be used, although in a preferred embodiment of the invention, the microarray reading device of the invention comprises a means for applying drops of aqueous medium.
- the means for applying drops of aqueous medium is integrated in the microarray reading device itself, and comprises a reservoir of aqueous medium coupled to the surface of the base opposite the reading surface, and a matrix of microchannels made in The device's own base.
- Each microchannel connects the tank of aqueous medium with the point where each transducer is located, so that by modifying the pressure in the tank a controlled injection of aqueous medium is achieved, thus forming drops of uniform volume on top of each transducer.
- the aqueous medium reservoir comprises an inlet and an outlet of aqueous medium, so that different liquids can be injected therewith.
- the aqueous medium drop application medium is an applicator comprising an aqueous medium reservoir and a matrix of microchannels practiced on one of its walls.
- the injection of fluid onto each transducer occurs until it is form a drop of the desired volume.
- This can be done by directly forming a single drop or by depositing a multitude of small droplets ejected from the nozzle of the microchannel by some mechanism similar to that used by the inkjet printers, and which, upon joining the transducer, form the drop.
- Being an applicator that is not integrated in the base it is necessary to position it so that each Microchannel faces a transducer. For this, the same support means used to place the microarray can be used.
- Reading means connected to the transducers, that interpret the electrical signals of the transducers.
- the enzymatic reaction begins to take place.
- the transducer will measure a greater change in the concentration of products.
- the drops are separated from each other and therefore the products accumulate in the volume thereof without interference between different points of the matrix. Therefore, the transducer matrix is connected to electronic measurement circuits capable of acquiring and processing the signal generated by each of said transducers.
- the measurement can be made at the end of a certain time or for as long as the drops are in contact with the spots.
- the second case allows measuring the dynamics of the enzymatic reaction, which can give more analytical information. For example, it may allow a greater dynamic range, since the evolution of product concentrations can be detected before a saturation value is reached.
- an electrical reading method of a microarray is described using the reading device described above, which comprises the following operations:
- drops of aqueous medium can be created first on the transducers, and then placed the microarray, with the aid of some support means, parallel to the reading surface of the base, and at such a distance that each spot is faced with a transducer and the drop of aqueous medium touches them both.
- the chemical reaction between the chemical substrate included in the aqueous medium and the enzymatic brand of the spot begins, forming as a result of the reaction products that modify some electrical property or chemistry of the aqueous medium that forms the drop.
- the subsequent reading operation can be performed, either simultaneously on all transducers of the matrix, or sequentially by rows, columns or individually.
- the base of the device so that there are no remains of the products of Ia Enzymatic reaction or enzymes that may have detached from the microarray.
- the cleaning solution or solutions must have the ability to dissolve the products of the enzymatic reaction and denature the enzymes so that they completely lose their activity. Cleaning can end with a rinse in deionized water.
- This cleaning can be done in a traditional way or, in accordance with a particular embodiment of the invention, by sucking the drops of aqueous medium generated and then injecting a cleaning solution, by means of applying drops of aqueous medium.
- the means for applying drops of aqueous medium must be capable of creating negative pressures in the reservoir to which the microchannels are connected and of replacing the aqueous medium of the reservoir with a suitable cleaning solution.
- Figure 1. It shows a scheme of a flat support microarray, with the different parts that compose it.
- Figures 2.- Shows a diagram of an electric microarray reading device according to the invention.
- Figures 3 and A Show two particular embodiments of means of application of drops of aqueous medium.
- Figures 5 and 6.- Shows the first operations of the microarray electric reading procedure according to a particular embodiment of the invention.
- Figure 7.- Shows a particular embodiment of the reading means according to the present invention.
- Figure 1 shows a microarray (6) formed by a flat support (9), on whose test surface (7) an array of measuring points or spots (8) are arranged, which are marked with an enzymatic mark.
- Figure 2 schematically shows the microarray reading device (1) according to the present invention. It is observed that it is formed by a base (2), on whose reading surface (4) there is a matrix of transducers (5) that react to a change in an electrical or chemical property of the aqueous medium.
- the device (1) for reading microarrays of electric and reusable type of the example further comprises, on the sides of the base (2), support means (3), which serve to support the microarray (6) so that each spot (8) of the matrix is facing a transducer
- the support means (3) basically comprise a flange that supports the microarray (6) during the reading process.
- the reading means (10) which are they have represented in Fig. 7.
- the manufacture of the base (2) and the transducer matrix (5) is made from pyrex glass wafers of 100 mm diameter.
- the process begins with the deposition of a titanium, nickel and gold metal trilayer (the titanium is deposited on the pyrex with a thickness of 20 nm, the nickel on the titanium with a thickness of 50 nm and the gold on the nickel with a 50 nm thickness).
- the three metals are deposited by sputtering.
- a standard photolithography process is then carried out with a mask that contains the reasons for defining an array of pairs of interdigitated electrodes. Each pair of interdigitated electrodes has 14 fingers (seven on each electrode) 20 ⁇ m wide, 20 ⁇ m apart and with an interdigitated zone length of 500 ⁇ m.
- connection tracks are defined that go from each electrode to the edge of the chip, where an area is defined for its connection to a printed circuit by means of wire welding.
- the transducers form a rectangular matrix of 4x9 elements and are 6 mm apart between them. In a 100 mm wafer, two arrays of transducers (5) fit as described.
- the attack of the metals after the photolithography is carried out in different attack solutions.
- For the gold a mixture of 5700 ml of H 2 O, 435 g of Kl and 250 g of I 2 is used .
- nickel a 1: 4 mixture of 70% HNO3: H 2 O is used.
- titanium a 1: 10: 33 mixture of 49% HF: H 2 O: 1, 2-Propanediol is used.
- the wafer is passed through a mechanical saw to separate the two transducer matrices (5).
- the matrices are joined to a printed circuit in which the areas necessary for the connection by means of wire welding have been defined and which has a connector to electrically connect the electrodes to the instrumentation.
- the wires are protected by a thermosetting polymer (Epotek H77).
- the means of support (3) is manufactured with Polydimethylsloxane from a mold, and is welded to the transducer matrix by activation with oxygen plasma.
- Figures 3 and 4 show respectively two preferred embodiments of aqueous medium application media.
- these are integrated in the base (2 '), so that a tank
- each transducer (5 ') has a central hole where the nozzle of each microchannel is.
- the means of application of aqueous medium constitute an applicator formed by a reservoir (11 ") of aqueous medium in one of whose walls there are microchannels (12"), through which the aqueous medium is injected onto the transducers (5 ").
- the support means (3 ") further comprise a second flange on which the aqueous medium applicator rests.
- Figures 5 and 6 show some operations of a preferred embodiment of the process of the invention.
- Figure 5 shows the micrroarray (6) and the reading device (1), where the operation of injecting a drop of aqueous medium on each transducer (5) has previously been carried out.
- the microarray (6) is already prepared to be supported on the support means (3), moment that is collected in Figure 6, in which each drop of aqueous medium is already in contact with a spot (8), and by The chemical reaction between the enzymatic brand and the substrate has already begun.
- Figure 7 shows the measurement instrumentation in the If the product of the chemical reaction between the enzymatic brand and the chemical substrate causes changes in the impedance of the aqueous medium of the drop.
- the instrumentation comprises sources of alternating voltage excitation (15) and measuring circuits (16) of alternating current, which combined are capable of measuring the impedance seen in terminals of the interdigitated electrodes (17).
- the figure shows the connection of said sources (15) and measuring circuits (16) with the electrodes (17).
- the impedance transducers allow a row-column type connection. This makes practical the realization of matrices of large number of elements. For example, for a matrix of 1024 elements, 32 sources of alternating excitation (15) and 32 measuring circuits (16) of the current would suffice.
- the current measurement circuits (16) have been implemented in the example with AD8674 operational amplifiers, with a precision feedback resistance of 100 k ⁇ .
- the recording of the voltage values at the output of the operational amplifiers has been carried out by means of the analog inputs of the same card.
- a program in LabView is used to control the acquisition process, process the acquired signals and obtain the impedance values presented by the transducers (5) over the reading time.
- the acquisition process is developed according to the following sequence: First it excites a row of transducers (5) with an alternating voltage of 50 mV amplitude and 2 kHz frequency for 25 ms. The remaining sources (15) of excitation are maintained at OV. During this time the signal is acquired with the analog inputs connected to each of the transducer columns (5). Then we would proceed in the same way with the next row and so on until all rows of transducers had been read.
- Ureasa in the presence of urea (neutral) produces ammonia and carbon dioxide.
- the ammonia is rapidly protonated giving rise to the ammonium ion (positively charged), while the carbon dioxide will partially become bicarbonate (negatively charged). Therefore, the enzymatic reaction increases the conductivity of the original buffer.
- the original buffer is formed by an aqueous solution of 0.1 M urea and 0.25 M glycine, with an approximate conductivity of 16 ⁇ S / cm.
- the 1 ⁇ l volume buffer drops were deposited onto the transducers (5) manually using a micropipette.
- a rabbit analyte G was used as a model analyte and a reverse phase type assay was applied. This consisted of making successive dilutions of a stock solution of said model analyte. Micro-drops of 1 ⁇ l_ volume were deposited, of each of the dilutions prepared in the support (9) of the microarray (6) (previously silanized glass slides). Once the analyte was immobilized, the microarray (6) was incubated with a solution of a goat antibody, rabbit anti-immunoglobulin G labeled with urease for one hour, during which time the specific interaction between the analyte and labeled antibody. After washing the microarray (6) with deionized water and drying in a stream of nitrogen, the reading was carried out with the matrix of impedance transducers (5).
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- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Immunology (AREA)
- Electrochemistry (AREA)
- General Physics & Mathematics (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
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- Hematology (AREA)
- Molecular Biology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/737,438 US20110152124A1 (en) | 2008-07-11 | 2009-07-08 | Electrical and reusable device for reading microarrays |
CN2009801269807A CN102089648A (zh) | 2008-07-11 | 2009-07-08 | 用于读取微阵列的电气可重用设备 |
JP2011517182A JP2011527427A (ja) | 2008-07-11 | 2009-07-08 | マイクロアレイ読み取りのための再利用可能な電気装置 |
CA2730644A CA2730644A1 (en) | 2008-07-11 | 2009-07-08 | Electrical and reusable device for reading microarrays |
EP09793983A EP2302370A1 (en) | 2008-07-11 | 2009-07-08 | Electrical and reusable device for reading microarrays |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ESP200802068 | 2008-07-11 | ||
ES200802068A ES2334745B1 (es) | 2008-07-11 | 2008-07-11 | Dispositivo de lectura de microarrays de tipo electrico y reutilizable. |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2010004075A1 true WO2010004075A1 (es) | 2010-01-14 |
Family
ID=41506719
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/ES2009/070278 WO2010004075A1 (es) | 2008-07-11 | 2009-07-08 | Dispositivo de lectura de microarrays de tipo eléctrico y reutilizable |
Country Status (8)
Country | Link |
---|---|
US (1) | US20110152124A1 (es) |
EP (1) | EP2302370A1 (es) |
JP (1) | JP2011527427A (es) |
KR (1) | KR20110034661A (es) |
CN (1) | CN102089648A (es) |
CA (1) | CA2730644A1 (es) |
ES (1) | ES2334745B1 (es) |
WO (1) | WO2010004075A1 (es) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2017092875A1 (en) | 2015-12-02 | 2017-06-08 | Boehringer Ingelheim Vetmedica Gmbh | Method for producing a plurality of measurement regions on a chip and chip having a plurality of measurement regions |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US20050106742A1 (en) * | 2003-08-30 | 2005-05-19 | Hans-Peter Wahl | Method and device for determining analytes in a liquid |
WO2006026796A1 (de) | 2004-09-08 | 2006-03-16 | Nanoident Technologies Ag | Vorrichtung zum auswerten biochemischer proben |
WO2008051196A2 (en) | 2005-09-21 | 2008-05-02 | Combimatrix Corporation | Process to detect binding events on an electrode microarray using enzymes |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
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JP4320069B2 (ja) * | 1998-09-28 | 2009-08-26 | セイコーエプソン株式会社 | センサーデバイス作成方法 |
JP2001083158A (ja) * | 1999-09-17 | 2001-03-30 | Fuji Photo Film Co Ltd | マクロアレイと支持具を用いた分析方法とその為の用具 |
WO2003012147A1 (en) * | 2001-02-20 | 2003-02-13 | Datascope Investment Corp. | Method for reusing standard blots and microarrays utilizing dna dendrimer technology |
CN1605861A (zh) * | 2004-11-15 | 2005-04-13 | 东南大学 | 电化学定量聚合酶链式反应检测芯片的制备和检测方法 |
JP3930517B2 (ja) * | 2005-03-23 | 2007-06-13 | 株式会社東芝 | 生体分子の定量分析チップ、及び、定量分析方法、定量分析装置及びシステム |
US7453916B2 (en) * | 2005-09-08 | 2008-11-18 | Intel Corporation | High throughput optical micro-array reader capable of variable pitch and spot size array processing for genomics and proteomics |
-
2008
- 2008-07-11 ES ES200802068A patent/ES2334745B1/es not_active Expired - Fee Related
-
2009
- 2009-07-08 US US12/737,438 patent/US20110152124A1/en not_active Abandoned
- 2009-07-08 WO PCT/ES2009/070278 patent/WO2010004075A1/es active Application Filing
- 2009-07-08 EP EP09793983A patent/EP2302370A1/en not_active Withdrawn
- 2009-07-08 KR KR1020117002956A patent/KR20110034661A/ko not_active Application Discontinuation
- 2009-07-08 JP JP2011517182A patent/JP2011527427A/ja active Pending
- 2009-07-08 CA CA2730644A patent/CA2730644A1/en not_active Abandoned
- 2009-07-08 CN CN2009801269807A patent/CN102089648A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050106742A1 (en) * | 2003-08-30 | 2005-05-19 | Hans-Peter Wahl | Method and device for determining analytes in a liquid |
WO2006026796A1 (de) | 2004-09-08 | 2006-03-16 | Nanoident Technologies Ag | Vorrichtung zum auswerten biochemischer proben |
WO2008051196A2 (en) | 2005-09-21 | 2008-05-02 | Combimatrix Corporation | Process to detect binding events on an electrode microarray using enzymes |
Non-Patent Citations (1)
Title |
---|
DE THE RICA, R ET AL.: "Local detection of enzymatic ion generatiom with polycrystalline silicon interdigitated elctrodes and its application to biosensing.", APPLIED PHYSICS LETTERS, vol. 90, 2007, XP012096094 * |
Also Published As
Publication number | Publication date |
---|---|
EP2302370A1 (en) | 2011-03-30 |
CN102089648A (zh) | 2011-06-08 |
JP2011527427A (ja) | 2011-10-27 |
KR20110034661A (ko) | 2011-04-05 |
ES2334745A1 (es) | 2010-03-15 |
ES2334745B1 (es) | 2011-02-14 |
CA2730644A1 (en) | 2010-01-14 |
US20110152124A1 (en) | 2011-06-23 |
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