WO2001014866A1 - Silicon-based multisensor microsystem - Google Patents

Silicon-based multisensor microsystem Download PDF

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Publication number
WO2001014866A1
WO2001014866A1 PCT/ES2000/000328 ES0000328W WO0114866A1 WO 2001014866 A1 WO2001014866 A1 WO 2001014866A1 ES 0000328 W ES0000328 W ES 0000328W WO 0114866 A1 WO0114866 A1 WO 0114866A1
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WIPO (PCT)
Prior art keywords
sensors
microsystem
sensor
tissue
microsystem according
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PCT/ES2000/000328
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Spanish (es)
French (fr)
Inventor
Jordi Aguilo Llobet
Rubén CORONEL
Raúl ARBUES
Joan Cinca
Eric Mcadams
Paolo Dario
Original Assignee
Consejo Superior De Investigaciones Cientificas
University Of Amsterdam
D+T Microelectronica, A.I.E.
Hospital Universitari Vall D'hebron
Northern Ireland Bio Engineering Center
Scuola Superiore Santa Anna
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Application filed by Consejo Superior De Investigaciones Cientificas, University Of Amsterdam, D+T Microelectronica, A.I.E., Hospital Universitari Vall D'hebron, Northern Ireland Bio Engineering Center, Scuola Superiore Santa Anna filed Critical Consejo Superior De Investigaciones Cientificas
Priority to AU68432/00A priority Critical patent/AU6843200A/en
Publication of WO2001014866A1 publication Critical patent/WO2001014866A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14542—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring blood gases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/053—Measuring electrical impedance or conductance of a portion of the body
    • A61B5/0538—Measuring electrical impedance or conductance of a portion of the body invasively, e.g. using a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14539—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring pH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6848—Needles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/413—Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant

Abstract

The invention relates to a compact, millimeter-size silicon-based multisensor microsystem having the shape of a needle and comprising a series of sensors (to measure pH, analytes such K+, sensors to measure impedance, temperature, etc.). Said microsystem also comprises pre-processing and signal amplification circuitry and telemetric circuitry of more than 3 megabits for short-distance data transmission. Said system is designed and optimized for applications in the field of medicine, more particularly, it can be used in tissue characterization and monitoring by inserting the system into a tissue, organ or body fluid.

Description

1. Título.1. Title.
Microsistema multisensor basado en silicio.Multisensor microsystem based on silicon.
2. Sector de la Técnica. Esta invención se encuadra en el sector de tecnología de semiconductores en lo que al proceso de fabricación se refiere y en el sector médico en cuanto a la aplicación.2. Technical Sector. This invention falls within the semiconductor technology sector as regards the manufacturing process and in the medical sector as regards the application.
3. Estado de la Técnica3. State of the Art
En los últimos años se han desarrollado gran número de sensores basados en tecnologías microelectrónicas. De entre estos desarrollos es ampliamente conocido el sensor ISFET (ion sensitive field transistor). Dicho dispositivo es básicamente un transistor MOS (Metal-Oxido-Semiconductor) al que se le ha sustituido el metal de la puerta por una solución iónica que contiene el ion a analizar. Patentes como US 4020830 utilizan uno de estos transductores (chemical sensitive field-effect transistor), para detectar y medir las propiedades químicas de las sustancias a las cuales el transductor está expuesto.In recent years, a large number of sensors based on microelectronic technologies have been developed. Among these developments, the ISFET (ion sensitive field transistor) sensor is widely known. Said device is basically an MOS transistor (Metal-Oxide-Semiconductor) to which the metal of the door has been replaced by an ionic solution containing the ion to be analyzed. Patents such as US 4020830 use one of these transducers (chemical sensitive field-effect transistor), to detect and measure the chemical properties of the substances to which the transducer is exposed.
La patente US 5387328 (SENSOR TECHNOLOGY RESEARCH CENTER OF KYUNGPOOK NATIONAL UNIVERSITY - Bio-Sensor Using Ion Sensitive field effect transistor with platinium electrode) utiliza nuevamente el sensor ISFET, esta vez para la obtención de un biosensor capaz de medir glucosa y añadiendo un electrodo de Pt para aumentar la sensibilidad y reducir el tiempo de reacción del sensor. Existen igualmente otras patentes que proponen el uso de un dispositivo multisensor, como la patente número US 4874500 ( SRI International - Microelectrochemical sensor and sensor array) . En esta patente se usa una serie de electrodos amperométricos para la medida de CO , O2, K+, H+ . El método de medida utilizado en esta patente, difiere pues del propuesto en la presente patente en el método de medida, ya que usa un método amperométrico, electrodos amperométricos, en lugar de sensores conductimétricos basados en ISFETs. En la columna 1, líneas 27-50 de esta patente se explica el número de problemas que tienen los sensores ISFETs para la estabilidad, fabricación y obtención del electrodo de referencia. Dichos problemas están resueltos en nuestra invención. Otra diferencia encontrada es el tipo de aplicación , pues no es posible hacer medidas dinámicas. En esta patente se sugiere que el sistema podría estar provisto de un circuito integrado para la amplificación o tratamiento de la señal, pero dicho circuito no figura descrito.US 5387328 (SENSOR TECHNOLOGY RESEARCH CENTER OF KYUNGPOOK NATIONAL UNIVERSITY - Bio-Sensor Using Ion Sensitive field effect transistor with platinium electrode) uses the ISFET sensor again, this time to obtain a biosensor capable of measuring glucose and adding an electrode Pt to increase sensitivity and reduce sensor reaction time. There are also other patents that propose the use of a multi-sensor device, such as US Patent No. 4874500 (SRI International - Microelectrochemical sensor and sensor array). In this patent a series of amperometric electrodes is used for the measurement of CO, O 2 , K + , H + . The measurement method used in this patent thus differs from that proposed in the present patent in the measurement method, since it uses an amperometric method, amperometric electrodes, instead of conductivity sensors based on ISFETs. In column 1, lines 27-50 of this patent the number of problems that ISFETs sensors have for the stability, manufacture and obtaining of the reference electrode is explained. These problems are solved in our invention. Another difference found is the type of application, as it is not possible to make dynamic measurements In this patent it is suggested that the system could be provided with an integrated circuit for amplification or signal processing, but said circuit is not described.
Otra de las patentes referidas por el informe sobre el estado de la técnica es la número US 5394883 (CASE WESTERN RESERVE UNIVERSITY-Multiple Thin Film Sensor System). Esta patente se refiere a un sensor de flujo de aire que utiliza termoresistencias. Determina el flujo por la diferencia de temperatura entre el aire inyectado y la del aire ambiente. Los sensores utilizados son termoresistencias y la aplicación pretende monitorizar el flujo de aire de la respiración de una persona. Utilizan diversos termoresistencias (a veces necesitan calentar el aire para proceder a la medida del flujo) pero para realizar una única clase de medida, la del flujo del aire, luego no es un sistema multisensor. Esta invención tiene pues aplicación, tecnología y sensores totalmente diferentes a lo propuesto en la presente patente.Another of the patents referred to in the state of the art report is number US 5394883 (CASE WESTERN RESERVE UNIVERSITY-Multiple Thin Film Sensor System). This patent refers to an air flow sensor that uses heat resistance. Determine the flow by the temperature difference between the injected air and that of the ambient air. The sensors used are thermoresistances and the application aims to monitor the air flow of a person's breathing. They use various thermoresistances (sometimes they need to heat the air to proceed with the measurement of the flow) but to perform a single measurement class, that of the air flow, then it is not a multi-sensor system. This invention therefore has application, technology and sensors totally different from what is proposed in this patent.
La patente US 5393401 (Knoll, M.- Method of manufacturing miniaturized components of chemical and biological detection sensors that employ ion-selective membranes, and supports for such components)describe un método de fabricación de componentes miniaturizados de sensores de detección biológica y química y los soportes para dichos componentes.US 5393401 (Knoll, M.- Method of manufacturing miniaturized components of chemical and biological detection sensors that employ ion-selective membranes, and supports for such components) describes a method of manufacturing miniaturized components of biological and chemical detection sensors and the supports for said components.
La patente US 5846392 (Knoll, M.- Miniaturized circulatory measuring chamber with integrated chemo-and/or biosensors elements) describe un trabajo de microfluídica. La estructura presentada contrariamente a la que se pretende patentar no es superficial sino que es una cámara circulatoria con una serie de conductos. La aplicación, proceso de fabricación de estas dos invenciones son consecuentemente distintas.US Patent 5846392 (Knoll, M.- Miniaturized circulatory measuring chamber with integrated chemo-and / or biosensors elements) describes a microfluidic work. The structure presented contrary to the one intended to be patented is not superficial but is a circulatory chamber with a series of ducts. The application, manufacturing process of these two inventions are consequently different.
Por último, la patente US 5385659 (SIEMENS - reference electrode) describe un electrodo de referencia plano para sensores químicos. Es ampliamente conocido que el sensor ISFET necesita un electrodo de referencia para polarizar la puerta del dispositivo y poder desempeñar su función de sensor. En esta patente proponen un electrodo de referencia que puede ser un metal o un sensor, preferiblemente un sensor ISFET y recubierto por un polímero. Las diferencias observadas es que en la patente presente se pretende utilizar un electrodo de referencia ( ya que es necesario para la utilización del ISFET como sensor) metálico y utilizando pues procesos de fabricación distintos para integrarlo con el resto de los elementos del sistema. Además de no utilizar el sistema de difusión mediante capas de polímeros descrito en la patente US 5385659.Finally, US 5385659 (SIEMENS - reference electrode) describes a flat reference electrode for chemical sensors. It is widely known that the ISFET sensor needs a reference electrode to polarize the device door and be able to perform its sensor function. In this patent they propose an electrode of reference that can be a metal or a sensor, preferably an ISFET sensor and coated by a polymer. The differences observed is that in the present patent it is intended to use a reference electrode (since it is necessary for the use of the metallic ISFET) and using different manufacturing processes to integrate it with the rest of the system elements. In addition to not using the diffusion system using polymer layers described in US 5385659.
Se citan a continuación una serie de grupos que trabajan en el desarrollo de sistemas con cierta similitud a la invención del presente documento. A series of groups that work on the development of systems with some similarity to the invention of this document are cited below.
Figure imgf000006_0001
4. Descripción de la invención.
Figure imgf000006_0001
4. Description of the invention.
4.1. Breve descripción de la invención.4.1. Brief description of the invention.
La novedad que se presenta es la realización de un microsistema multisensor basado en silicio de reducidas dimensiones del orden de milímetros (un ejemplo de realización podría ser de estas dimensiones aproximadas, 8 x 1.1 x 0.5 mm) de forma es similar a una aguja y con un extremo o cabeza de mayor grosor. En la parte estrecha se disponen una serie de sensores. Una posible realización de incluir un sensor de K+, un sensor de pH y un sensor de temperatura, y cuatro electrodos de platino. La forma facilita su inserción en tejidos u órganos así como el anclaje del dispositivo en el tejido. En la parte proximal o más ancha se conectan circuitos de baja potencia/bajo ruido para tratamiento y condicionamiento de las señales así como la circuitera de telemetría para transmisión de estos datos. El sistema también es aplicable para la medición de otros tipos de iones Na+, Ca2+, etc.The novelty presented is the realization of a multisensor microsystem based on silicon of small dimensions of the order of millimeters (an example of embodiment could be of these approximate dimensions, 8 x 1.1 x 0.5 mm) so it is similar to a needle and with one end or head of greater thickness. In the narrow part a series of sensors are arranged. A possible embodiment of including a K + sensor, a pH sensor and a temperature sensor, and four platinum electrodes. The shape facilitates its insertion into tissues or organs as well as the anchoring of the device in the tissue. In the proximal or wider part, low power / low noise circuits are connected for signal processing and conditioning as well as the telemetry circuitry for transmission of this data. The system is also applicable for the measurement of other types of Na +, Ca2 + ions, etc.
Su utilidad es para efectuar una monitorización continua y simultanea de cambios en la impedancia , concentración de iones tales como el K+ extracelular, y también de pH y temperatura de tejidos , órganos o líquidos corporalesIts usefulness is to carry out a continuous and simultaneous monitoring of changes in impedance, concentration of ions such as extracellular K +, and also of pH and temperature of tissues, organs or body fluids
La innovación inventiva esta en la compatibilizazión de tecnologías y desarrollo de procesos tecnológicos en silicio que permita la incorporación simultanea en el mismo microsistema de diferentes elementos captadores de señales, así como su adecuación para uso biomédico.The inventive innovation is in the compatibilization of technologies and development of technological processes in silicon that allows the simultaneous incorporation in the same microsystem of different signal capture elements, as well as their adaptation for biomedical use.
4.2. Descripción detallada de la invención. Tal como se muestra esquemáticamente en la figural , la lanceta está constituida por una fina aguja de silicio en la que se sitúan cuatro pares de electrodos de platino para la medida de impedancias junto con cuatro dispositivos ISFET sensibles a la concentración de iones hidrógeno (H+), puesto que el aislante de puerta es el material inorgánico nitruro de silicio (Si3N4). Estos materiales depositados en forma de capas delgadas pueden servir, también, como substratos para la deposición de membranas poliméricas sensibles a determinado tipo de iones. Los dispositivos obtenidos con la incorporación de estas membranas se denominan MEMFETs (Membrane Field-Effect Transistor). Por tanto, se va depositar en uno de los ISFET una membrana selectiva al ion potasio y en otro una membrana insensible al pH y al pK con el objetivo de realizar medidas diferenciales de las concentraciones de H+ y K+. Una o dos de estas lancetas, según el modelo, serán encapsuladas en silicona junto con la 'circuitería adecuada de preamplificación y acondicionamiento de señal, de multiplexación y de telemetría para la transmisión de las medidas efectuadas a un sistema receptor multicanal situado a una distancia entre 1 y 5 metros.4.2. Detailed description of the invention. As shown schematically in the figural, the lancet is constituted by a thin silicon needle in which four pairs of platinum electrodes are placed for the measurement of impedances together with four ISFET devices sensitive to the concentration of hydrogen ions (H + ), since the door insulator is the inorganic silicon nitride material (Si 3 N 4 ). These materials deposited in the form of thin layers can also serve as substrates for the deposition of polymer membranes sensitive to certain types of ions. The devices obtained with the Incorporation of these membranes are called MEMFETs (Membrane Field-Effect Transistor). Therefore, a potassium ion selective membrane is deposited in one of the ISFETs and a pH and pK insensitive membrane in another with the objective of making differential measurements of the H + and K + concentrations. One or two of these lancets, depending on the model, will be encapsulated in silicone together with the appropriate signal preamplification and conditioning circuitry, multiplexing and telemetry circuitry for the transmission of the measurements made to a multichannel receiver system located at a distance between 1 and 5 meters.
Tecnología de los biosensoresBiosensor Technology
Sensor de pHPH sensor
Se utilizan transistores de efecto de campo selectivo a iones (ISFET), es decir sensores químicos de estado sólido sensibles al pH donde el potencial de la interfase óxido- electrolito ( Ψ0) se utiliza, para modular una resistencia que junto con el potencial aplicado al drenador respecto a la fuente (Vus) determina el valor de la corriente Iαs que circula entre drenador y la fuente y por tanto Ius variará con la concentración de la solución. Se utiliza la tecnología NMOS compatible con la tecnología CMOS del Centro Nacional de Microelectrónica. Los niveles de máscara son 7.Ion-selective field effect transistors (ISFET) are used, ie pH sensitive solid state chemical sensors where the potential of the oxide-electrolyte interface (Ψ 0 ) is used, to modulate a resistance that together with the applied potential the drain relative to the source (V us ) determines the value of the current I αs flowing between the drain and the source and therefore I us will vary with the concentration of the solution. The NMOS technology compatible with the CMOS technology of the National Microelectronics Center is used. The mask levels are 7.
Se parte de obleas de silicio <100>, tipo p dopados con impurezas de boro. En este substrato se forman dos regiones de dopaje diferente a la propia del silicio, fuente y drenador. En primer lugar se realiza la oxidación del campo como capa protectora para la difusión selectiva de fuente y drenador. Implantación de fósforo para formar las regiones de fuente y drenador (n+). Fotolitografía y grabado del óxido, definiendo la puerta del ISFET (canal). Crecimiento del óxido delgado de puerta. Deposición de una capa de nitruro de silicio (membrana inorgánica sensible al pH, SÍ3N4), fotolitografía y grabado. Deposición del platino (Lift-Off) par constituir el electrodo de referencia que polarizará el dispositivo.It starts from silicon wafers <100>, type p doped with boron impurities. In this substrate, two different doping regions are formed than that of the silicon, source and drain. First, the oxidation of the field is carried out as a protective layer for the selective diffusion of source and drain. Phosphorus implantation to form the source and drain regions (n +). Photolithography and engraving of rust, defining the door of the ISFET (channel). Growth of thin gate rust. Deposition of a silicon nitride layer (pH sensitive inorganic membrane, SÍ3N4), photolithography and etching. Platinum deposition (Lift-Off) to constitute the reference electrode that will polarize the device.
Pasivación para protección del dispositivo y apertura de la puerta y contactos. Definición de la lanceta empleando una capa de aluminio como máscara.Passivation for protection of the device and opening of the door and contacts. Definition of the lancet using an aluminum layer as a mask.
Decapado del aluminio.Pickling of aluminum.
Sensor de K+K + sensor
Se utiliza un dispositivo MEMFET. El MEMFET resulta al modificar la estructura del ISFET. Esta modificación consiste en depositar una membrana polimérica en la región activa de la puerta del ISFET, a fin de obtener un dispositivo sensible a un ion determinado. En nuestro caso el dispositivo es sensible al K+.A MEMFET device is used. MEMFET results when the structure of the ISFET is modified. This modification consists in depositing a polymeric membrane in the active region of the ISFET door, in order to obtain a device sensitive to a specific ion. In our case the device is sensitive to K +.
Electrodo de platinoPlatinum electrode
El electrodo de Pt para medir la impedancia y el electrodo de Pt que actúa como electrodo de referencia se realizan en el mismo proceso tal como indicado en el caso del sensor de pH.The Pt electrode for measuring the impedance and the Pt electrode that acts as the reference electrode are performed in the same process as indicated in the case of the pH sensor.
Circuito integrado para la adquisición de datos y telemetríaIntegrated circuit for data acquisition and telemetry
El circuito integrado se encarga de generar las señales necesarias para la excitación de los electrodos y biosensores, registrar las medidas adquiridas y acondicionar las respuestas de los electrodos y biosensores.The integrated circuit is responsible for generating the necessary signals for the excitation of the electrodes and biosensors, recording the acquired measurements and conditioning the responses of the electrodes and biosensors.
Para la realización de medidas de impedancia se aplica una corriente alterna a través de los electrodos externos y se determina los componentes de fase y de cuadratura de la caída de tensión de los electrodos internos. Un ejemplo de realización de este circuito se detalla en las figuras 16-22, entendiéndose que la topología del circuito puede variar y no tiene que ser la expuesta en este ejemplo.For the realization of impedance measurements an alternating current is applied through the external electrodes and the phase and quadrature components of the voltage drop of the internal electrodes are determined. An exemplary embodiment of this circuit is detailed in Figures 16-22, it being understood that the topology of the circuit may vary and does not have to be set forth in this example.
De una forma muy similar, señales específicas son aplicadas al ISFET a fin de obtener lecturas de concentración de pH, K+ u otra especie que se quiera medir. Las señales de salida serán digitalizadas por un conversor A/D y enviadas a la instrumentación externa. Cuando la aplicación lo permita, se podrá evitar el uso del sistema de telemetría, y en su lugar se utilizará una conexión física entre el microsistema y la instrumentación externa. 5. Descripción detallada de los dibujos.In a very similar way, specific signals are applied to the ISFET in order to obtain concentration readings of pH, K + or other species to be measured. The output signals will be digitized by an A / D converter and sent to the external instrumentation. When the application allows it, the use of the telemetry system can be avoided, and instead a physical connection between the microsystem and external instrumentation will be used. 5. Detailed description of the drawings.
La figura 1 muestra la aguja con los sensores.Figure 1 shows the needle with the sensors.
Las figuras 2-15 ilustran las principales etapas del proceso de fabricación de los sensores químicos en las lancetas. La figura 16 muestra un esquema de una posible realización del circuito de medida de impedancia incluyendo excitación y medida. La figura 17 es una realización del circuito de excitación sinuosidal. La figura 18 muestra el detalle del generador AC de la figura 17. La figura 19 muestra el detalle del BPF y del Output-Buffer de la figura 17. La figura 20 es un ejemplo de realización del circuito de medida. La figura 21 es el detalle de la medida de módulo y fase de la figura 20. La figura 22 es el detalle de la figura 20 de conversor AD.Figures 2-15 illustrate the main stages of the manufacturing process of the chemical sensors in the lancets. Figure 16 shows a diagram of a possible embodiment of the impedance measurement circuit including excitation and measurement. Figure 17 is an embodiment of the sinuous excitation circuit. Figure 18 shows the detail of the AC generator of Figure 17. Figure 19 shows the detail of the BPF and the Output-Buffer of Figure 17. Figure 20 is an exemplary embodiment of the measuring circuit. Figure 21 is the detail of the module and phase measurement of Figure 20. Figure 22 is the detail of Figure 20 of AD converter.
6. Ejemplo de realización de la invención.6. Example of embodiment of the invention.
El sistema esta diseñado y optimizado para aplicaciones en el campo médico. En concreto su utilidad es para la caracterización y monitorización tisular mediante la inserción del sistema en un tejido u órgano o fluido corporal. Los parámetros físico- químicos a registrar pueden variar dependiendo de la aplicación en concreto. Parámetros iniciales, que se consideran standard, son temperatura; pH, K e impedancia tisular.The system is designed and optimized for applications in the medical field. Specifically, its usefulness is for tissue characterization and monitoring by inserting the system into a tissue or organ or body fluid. The physical-chemical parameters to be recorded may vary depending on the specific application. Initial parameters, which are considered standard, are temperature; pH, K and tissue impedance.
Uno de los usos de esta invención es la implantación de la lanceta para la medida de la impedancia del tejido del miocardio así como la medida de la concentración de iones H+ y K+ para su aplicación durante operaciones quirúrgica a corazón abierto durante las cuales el electrocardiograma no puede proporcionar información alguna sobre el estado del tejido ni de su evoluciónOne of the uses of this invention is the implantation of the lancet for the measurement of the impedance of the myocardial tissue as well as the measurement of the concentration of H + and K + ions for its application during open heart surgical operations during which the electrocardiogram does not can provide any information about the state of the tissue or its evolution
Otras Aplicaciones concretas identificadas:Other specific applications identified:
Monitorización tisular cardiaca durante la isquemia cardiaca provocada experimentalmente - Monitorización tisular cardiaca -on line- durante la cirugía extracorporea - Monitorización tisular de cualquier órgano durante la cirugía convencionalCardiac tissue monitoring during experimentally caused cardiac ischemia - Cardiac tissue monitoring -online- during extracorporeal surgery - Tissue monitoring of any organ during conventional surgery
Monitorización tisular de cualquier órgano durante la cirugía mínimamente invasiva. Monitorización y caracterización del metabolismo muscular esquelético Monitorización on line durante el transporte de órganos para transplante Monitorización on line de la evolución del rechazo de órganos transplantados. Monitorización y caracterización tisular on line de otros tejidos: cerebro, hígado. Monitorización y caracterización on line de tejidos tumorales. Monitorización y caracterización on line de fluidos corporales. Monitorización y caracterización del estado de conservación de alimentos. Monitorización y caracterización del medio ambiente. Tissue monitoring of any organ during minimally invasive surgery. Monitoring and characterization of skeletal muscle metabolism Online monitoring during transport of organs for transplantation Online monitoring of the evolution of rejection of transplanted organs. On-line tissue monitoring and characterization of other tissues: brain, liver. Online monitoring and characterization of tumor tissues. Online monitoring and characterization of body fluids. Monitoring and characterization of the state of food preservation. Monitoring and characterization of the environment.

Claims

7. Reivindicaciones. 7. Claims.
1.- Microsistema caracterizado por integrar en un substrato de silicio uno o más sensores, teniendo unas reducidas dimensiones, del orden de milímetros, y forma de aguja, incluyéndose además una circuitería de pre-procesamiento y amplificación de señales y una circuitería de telemetría para transmisión de datos a corta distancia.1.- Microsystem characterized by integrating in one silicon substrate one or more sensors, having reduced dimensions, of the order of millimeters, and needle shape, also including a pre-processing and signal amplification circuitry and a telemetry circuitry for short distance data transmission
2.- Microsistema según la reivindicación 1 en el que uno o más de los sensores son de tipo ISFET para la medida de analitos.2. Microsystem according to claim 1 wherein one or more of the sensors are of the ISFET type for analyte measurement.
3- Microsistema según la reivindicación 1 en el que uno o más de los sensores son conjuntos de electrodos para la medida de impedancias a cuatro hilos.3- Microsystem according to claim 1 wherein one or more of the sensors are sets of electrodes for measuring four wire impedances.
4.- Microsistema según la reivindicación 1 en el que uno o más de los sensores son resistencias metálicas para la medida de temperatura.4. Microsystem according to claim 1 wherein one or more of the sensors are metal resistors for temperature measurement.
5.- Microsistema según la reivindicación 1 caracterizado por tener una forma de aguja adecuada para facilitar su inserción y extracción de tejidos biológicos u otros materiales. Los sensores están localizados en el área que va a ser insertada en el tejido o material a analizar.5. Microsystem according to claim 1 characterized by having a needle shape suitable for easy insertion and removal of biological tissues or other materials. The sensors are located in the area that will be inserted into the tissue or material to be analyzed.
6.- Microsistema según la reivindicación 1 caracterizado por estar realizado con materiales biocompatibles o sistemas de revestimiento biocompatibles para ciertos componentes. 6. Microsystem according to claim 1 characterized in that it is made of biocompatible materials or biocompatible coating systems for certain components.
PCT/ES2000/000328 1999-08-23 2000-08-22 Silicon-based multisensor microsystem WO2001014866A1 (en)

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ESP9901923 1999-08-23
ES009901923A ES2154241B1 (en) 1999-08-23 1999-08-23 SILICON-BASED MULTISENSOR MICROSYSTEM.

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ES2154241A1 (en) 2001-03-16
ES2154241B1 (en) 2001-10-01

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