WO2015063540A1 - Microdevice of the lab-on-a-chip type, for identifying antibiotic sensitivity in the care point of the patient - Google Patents

Microdevice of the lab-on-a-chip type, for identifying antibiotic sensitivity in the care point of the patient Download PDF

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Publication number
WO2015063540A1
WO2015063540A1 PCT/IB2013/059726 IB2013059726W WO2015063540A1 WO 2015063540 A1 WO2015063540 A1 WO 2015063540A1 IB 2013059726 W IB2013059726 W IB 2013059726W WO 2015063540 A1 WO2015063540 A1 WO 2015063540A1
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Prior art keywords
micro
sample
antibiotic sensitivity
microdevice
micro device
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PCT/IB2013/059726
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Spanish (es)
French (fr)
Inventor
Sara DROGUETT BIZET
Mario SOTO AGUILERA
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Droguett Bizet Sara
Soto Aguilera Mario
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Priority to PCT/IB2013/059726 priority Critical patent/WO2015063540A1/en
Publication of WO2015063540A1 publication Critical patent/WO2015063540A1/en

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Classifications

    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • 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
    • B01L2300/0803—Disc shape
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces

Definitions

  • the present invention relates to the clinical diagnostic industry, in particular with the use of micro fluidic devices to carry out such diagnoses, such as blood gas analysis, molecular biology based tests, use of point immunoassay. of patient care.
  • lab-on-chips consist of self-sufficient diagnostic platforms in which, in principle, all diagnostic actions can be carried out by mixing between the different reagents, which run through the device and react in suitable cameras, to provide simple readings, usually by visual inspection, about the diagnosis.
  • the concept of lab-on-chip, today in most situations corresponds actually to chip-on-lab devices, that is, a simple microsystem, but that needs a set of machines, pumps , readers, pre-existing support structures in the analysis laboratory, for proper operation.
  • Current trends are aimed at achieving greater autonomy of these fluidic micro devices so that they can be used easily at the point of patient care.
  • microsystems for total analysis are the so-called microsystems for total analysis or " ⁇ -TAS" ("micro total analysis systems"), which can be conceived as advanced labs-on-chips or with greater integration of functions, thanks to the use of thermo-opto-electro-mechanical components with which a greater number of physical-chemical domains is controlled and more precise answers or with more information are obtained.
  • ⁇ -TAS micro total analysis systems
  • Diagnostic Strips consist of microfluidic devices for diagnosis at the point of extended and simpler patient care, generally oriented towards “all / nothing" diagnoses of the type "the patient has an infection”, “pregnancy tests” and similar ones. They are usually made of paper or very economical materials (polymers) and act by immersion of one of its ends in the sample under study, which by diffusion or by capillarity reaches different areas of the test strip and activates a color change, in case of positive diagnosis. Recently it is being investigated in the step of the traditional qualitative diagnosis using diagnostic strips to diagnoses with certain quantification.
  • micro devices described by the prior art corresponds to the so-called fluidic cartridges and integrated platforms, which correspond to complex systems composed of a hardware (desktop machine) with its own software for control of the analysis process in which cartridges are introduced fluids prepared with all reagents (as if it were a printer ink cartridge) and with the sample to be processed. They have communication ports for integration into hospital information systems and are often used for complex diagnoses, usually in the fields of genetics, molecular biology and the like.
  • a circular type device is available, preferably made of medical grade polymer, cyclic olefin or other material which has a microcamera to deposit the sample to be treated.
  • microcamera there is a plurality of microchannels, through which the sample will spread to at least one microwell, in which the process of identifying antibiotic sensitivity is developed.
  • Each of the microwells contains an antibiotic, a culture medium and a chromophore substance.
  • the antibiotics to be used would be those of routine use in medical practice, within which you can preferably use Pipedimic acid, Cephalotoxin, Ciprofloxacin, Cotrimozaxol, Gentamicin, Nitrofurantoin, Ampicillin, which does not exclude the use of other antibiotics
  • Each microchannel and each microwell are independent of the others to avoid cross contamination, so that the sample that diffuses from the microcamera has a unidirectional flow.
  • micro device of the invention allows to identify antibiotic sensitivity at the point of care of patients in areas, regions, medical facilities without attention 24 / 7, or in other types of facilities where there is a low level of equipment.
  • Another advantage is that it allows the ability to identify antibiotic sensitivity at the point of patient care without the need to refer the sample to centralized laboratories.
  • micro device is applicable to the performance of antibiogram by dilution according to customer requirements.
  • the micro device is adaptable to the epidemiological conditions of each country or region
  • the micro device also complies with ISO 13.485 certification for medical devices, which facilitates registration in destination countries.
  • Figure 1 is a view of a cover with perforations for micro wells of a two-piece model of a micro device according to an embodiment of the invention.
  • Figure 2 is a view of a substrate with micro channels of a two-piece model of a micro device according to an embodiment of the invention.
  • Figure 3 is a view of a one-piece micro device according to an embodiment of the invention.
  • Figure 4 is a view of a cover with perforations for micro wells and micro channels of a two-piece model of a micro device according to an embodiment of the invention.
  • Figure 5 is a view of a substrate with perforations for micro wells of a two-piece model of a micro device according to an embodiment of the invention.
  • Figure 6 is a pair of views of a mold for manufacturing a micro device according to an embodiment of the invention.
  • Figure 7 is a pair of mask views for manufacturing a micro device according to an embodiment of the invention. DETAILED DESCRIPTION OF THE INVENTION
  • the invention describes a micro-device or medical device (10) lab-on-chip type, capable of identifying antibiotic sensitivity at the point of care of patients, especially in rural areas, offices, hospitals that have no attention 24/7, hospitals with low level of equipment, ocean liners, among others.
  • the micro devices are used in patients with urinary tract infections and the sample to be used will be urine.
  • the device (10) has a circular type preference geometry, preferably 7 to 9 cm in diameter. Said device (10) is preferably manufactured from a medical grade polymer, cyclic olefin or other material I.
  • the micro device (10) has a microcamera (20) for depositing the sample.
  • microcamera (20) From said microcamera (20) a plurality of microchannels (30) leave, where each microchannel (30) diffuses to a respective circular microwell (40), in which the process of identifying antibiotic sensitivity is developed.
  • each of the microwells (40) of each device (10) contains an antibiotic, a culture medium and a chromophore substance.
  • the antibiotics to be used correspond to those of routine use in medical practice, within which you can preferably use Pipedimic acid, Cephalotoxin, Ciprofloxacin, Cotrimozaxol, Gentamicin, Nitrofurantoin, Ampicillin, which does not exclude use of other antibiotics
  • each microchannel (30) connects the microcamera (20) with its respective microwell (40), forming a structure preferably of radial symmetry.
  • Each microchannel (30) and each microwell (40) are independent of the others, to avoid cross contamination, so that the sample that diffuses from the microcamera must have unidirectional flow.
  • capillaries preferably between 300 and 600 microns in width and about 5 mm in length, provides reasonable values of channel travel times and allows their manufacture with the available technologies.
  • a series of manufacturing processes can be used to manufacture said micro devices (10).
  • the use of 2DV2 and 3D designs stands out, as well as the manufacturing technologies for UV photolithography and chemical attack, for laser stereolithography and for casting in silicone molds, since depending on the level of detail required, the productivity required or of the materials of interest, one can resort to the use of one or the other.
  • the designs of the micro devices (10) have a central circular zone for depositing the sample corresponding to the microcamera (20) and from which radial or microchannel rails (30) arise that connect with at least seven or eight external microwells (40) for reaction.
  • Different widths and heights have been tested for lanes, from 300 to 600 microns and, with total device diameters preferably ranging from 10 mm to 40 mm, which does not limit the use of larger diameter micro devices.
  • the first embodiment includes a lid (50) and a substrate (60), wherein said lid (50) has the perforation for the microcamera (20) and perforations for the plurality of microwells (40) as shown in Figure 1.
  • the substrate (60) incorporates the microchannels (30), as shown in Figure 2.
  • the microwells (40) have greater depth for reagent encapsulation and to produce anti-return effect once each microchannel (30) has been emptied by capillarity.
  • the micro device (10) is made up of a single piece with internal microchannels (30) that connect the microcamera (20) with each microwell (40) as shown in Figure 3, to take full advantage Additive manufacturing technologies.
  • the design of the micro device (10) is oriented to an improved encapsulation of the reagents, considering the additional use of an intermediate double-sided adhesive sheet that would be perforated at the point of previous patient care. to the use of the system.
  • the micro device (10) comprises a cover (70) and a substrate (80), wherein said cover (70) comprises perforations for the microcamera (20), for the plurality of microchannels (30) and for the microwells (40) as shown in Figure 4, and said substrate (80) comprises perforations for microwells (40), as shown in Figure 5.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention relates to a microdevice of the lab-on-a-chip type, which can identify the antibiotic sensitivity in the care point of the patient, especially in rural areas, practices, hospitals lacking round-the-clock care, hospitals with a poor level of equipment, inter alia, where said microdevice (10) has a preferably circular-type geometry and comprises a microchamber (20) in the centre of the microdevice (10), for storing the sample, where a plurality of microchannels (30)extend from said microchamber (20), and where each microchannel (30) distributes the sample to a respective microdish (40) wherein the process of identifying the antibiotic sensitivity is carried out.

Description

MEMORIA DESCIPTIVA  DESCIPTIVE MEMORY
CAMPO DE APLICACIÓN SCOPE
La presente invención se relaciona con la industria de diagnóstico clínico, en particular con el empleo de micro dispositivos fluídicos para llevar a cabo dicho tipo de diagnósticos, tales como análisis de gases en sangre, ensayos basados en Biología molecular, empleo de inmunoanálisis en el punto de atención del paciente. The present invention relates to the clinical diagnostic industry, in particular with the use of micro fluidic devices to carry out such diagnoses, such as blood gas analysis, molecular biology based tests, use of point immunoassay. of patient care.
ANTECEDENTES BACKGROUND
En la actualidad se conocen diferentes tipos de micro dispositivos fluídicos. Los laboratorios en un chip o "labs-on-chips" consisten de plataformas para diagnóstico autosuficientes en las que, en principio, todas las actuaciones del diagnóstico se pueden llevar a cabo mediante mezcla entre los distintos reactivos, que recorren el dispositivo y reaccionan en cámaras adecuadas, para aportar lecturas sencillas, generalmente por inspección visual, acerca del diagnóstico. Sin embargo, el concepto de lab-on-chip, a día de hoy, en la mayoría de las situaciones corresponde en realidad a dispositivos chip-on-lab, esto es, un microsistema sencillo, pero que necesita un conjunto de máquinas, bombas, lectores, estructuras de soporte preexistentes en el laboratorio de análisis, para su correcto funcionamiento. Las tendencias actuales van orientadas a conseguir una mayor autonomía de estos micro dispositivos fluídicos para que puedan emplearse de forma sencilla en el punto de atención al paciente. El documento US2009297403 describe un sistema del tipo lab-on-a-chip o biorreactor, además del método para elaborarlo. El sistema es complejo y tiene componentes cerámicos, sin embargo, a diferencia de otros documentos, éste sistema lab-on-a-chip permitiría el análisis de crecimiento celular bajo condiciones definidas o podría ser usado como un reactor microbiológico. At present, different types of fluidic micro devices are known. The laboratories on a chip or "labs-on-chips" consist of self-sufficient diagnostic platforms in which, in principle, all diagnostic actions can be carried out by mixing between the different reagents, which run through the device and react in suitable cameras, to provide simple readings, usually by visual inspection, about the diagnosis. However, the concept of lab-on-chip, today, in most situations corresponds actually to chip-on-lab devices, that is, a simple microsystem, but that needs a set of machines, pumps , readers, pre-existing support structures in the analysis laboratory, for proper operation. Current trends are aimed at achieving greater autonomy of these fluidic micro devices so that they can be used easily at the point of patient care. Document US2009297403 describes a system of the lab-on-a-chip or bioreactor type, in addition to the method for making it. The system is complex and has ceramic components, however, unlike others documents, this lab-on-a-chip system would allow the analysis of cell growth under defined conditions or could be used as a microbiological reactor.
Otro tipo de micro dispositivos son los denominados microsistemas para análisis total o "μ-TAS" ("micro total analysis systems"), los cuales se pueden concebir como labs-on-chips avanzados o con una mayor integración de funciones, gracias al empleo de componentes termo-opto-electro-mecánicos con los que se controla un mayor número de dominios físico-químicos y se obtienen respuestas más precisas o con más información. Another type of micro devices are the so-called microsystems for total analysis or "μ-TAS" ("micro total analysis systems"), which can be conceived as advanced labs-on-chips or with greater integration of functions, thanks to the use of thermo-opto-electro-mechanical components with which a greater number of physical-chemical domains is controlled and more precise answers or with more information are obtained.
El estado del arte también describe las denominadas Tiras Diagnósticas, que consisten en dispositivos microfluídicos para diagnóstico en el punto de atención al paciente más extendidos y más sencillos, generalmente orientados a diagnósticos "todo / nada" del tipo "el paciente tiene una infección", "tests de embarazo" y otros similares. Suelen estar fabricados en papel o en materiales muy económicos (polímeros) y actúan por inmersión de uno de sus extremos en la muestra objeto de estudio, que por difusión o por capilaridad llega a diferentes zonas de la tira reactiva y activa un cambio de color, en caso de diagnóstico positivo. Recientemente se está investigando en el paso del tradicional diagnóstico cualitativo empleando tiras diagnósticas a diagnósticos con cierta cuantificación. The state of the art also describes the so-called Diagnostic Strips, which consist of microfluidic devices for diagnosis at the point of extended and simpler patient care, generally oriented towards "all / nothing" diagnoses of the type "the patient has an infection", "pregnancy tests" and similar ones. They are usually made of paper or very economical materials (polymers) and act by immersion of one of its ends in the sample under study, which by diffusion or by capillarity reaches different areas of the test strip and activates a color change, in case of positive diagnosis. Recently it is being investigated in the step of the traditional qualitative diagnosis using diagnostic strips to diagnoses with certain quantification.
Otro tipo de micro dispositivos descrito por el arte previo corresponde a los denominados cartuchos fluídicos y plataformas integradas, los cuales corresponden a sistemas complejos compuestos por un hardware (máquina de sobremesa) con software propio para control del proceso de análisis en los que se introducen cartuchos fluídicos preparados con todos los reactivos (como si se tratara de un cartucho de tinta para impresora) y con la propia muestra a procesar. Tienen puertos de comunicación para su integración en los sistemas de información de los hospitales y suelen emplearse para diagnósticos complejos, generalmente en los campos de la genética, la Biología molecular y similares. Another type of micro devices described by the prior art corresponds to the so-called fluidic cartridges and integrated platforms, which correspond to complex systems composed of a hardware (desktop machine) with its own software for control of the analysis process in which cartridges are introduced fluids prepared with all reagents (as if it were a printer ink cartridge) and with the sample to be processed. They have communication ports for integration into hospital information systems and are often used for complex diagnoses, usually in the fields of genetics, molecular biology and the like.
PROBLEMA TÉCNICO TECHNICAL PROBLEM
Existe la necesidad de contar con un dispositivo que permita identificar la sensibilidad antibiótica en el punto de atención de los pacientes, especialmente en zonas rurales, consultorios, hospitales que no tiene atención 24 / 7, hospitales con escaso nivel del equipamiento, entre otros. There is a need for a device to identify antibiotic sensitivity at the point of patient care, especially in rural areas, offices, hospitals that do not have 24/7 care, hospitals with low level of equipment, among others.
SOLUCIÓN TÉCNICA TECHNICAL SOLUTION
Para solucionar dicha problemática, se dispone de un dispositivo de tipo circular, de preferencia fabricado en polímero de grado médico, olefina cíclica u otro material el cual cuenta con una microcámara para depositar la muestra a ser tratada. To solve this problem, a circular type device is available, preferably made of medical grade polymer, cyclic olefin or other material which has a microcamera to deposit the sample to be treated.
Desde dicha microcámara sale una pluralidad de microcanales, por los cuales difundirá la muestra hasta al menos un micropocillo, en el cual se desarrolla el proceso de identificación de la sensibilidad antibiótica. Cada uno de los micropocillos contiene un antibiótico, un medio de cultivo y una sustancia cromófora. Para el caso de las infecciones urinarias los antibióticos a emplear serían los de uso rutinario en la práctica médica, dentro de los cuales se pueden utilizar preferentemente Acido pipedimico, Cefalotoxina, Ciprofloxacino, Cotrimozaxol, Gentamicina, Nitrofurantoína, Ampicilina, lo cual no excluye el uso de otros antibióticos Cada microcanal y cada micropocillo son independientes de los otros para evitar contaminación cruzada, de modo la muestra que difunde desde la microcámara tiene un flujo unidireccional. From said microcamera there is a plurality of microchannels, through which the sample will spread to at least one microwell, in which the process of identifying antibiotic sensitivity is developed. Each of the microwells contains an antibiotic, a culture medium and a chromophore substance. In the case of urinary infections, the antibiotics to be used would be those of routine use in medical practice, within which you can preferably use Pipedimic acid, Cephalotoxin, Ciprofloxacin, Cotrimozaxol, Gentamicin, Nitrofurantoin, Ampicillin, which does not exclude the use of other antibiotics Each microchannel and each microwell are independent of the others to avoid cross contamination, so that the sample that diffuses from the microcamera has a unidirectional flow.
VENTAJAS TÉCNICAS TECHNICAL ADVANTAGES
Las ventajas técnicas que presenta el micro dispositivo de la invención es que, a diferencia de los micro dispositivos del estado del arte, su estructura permite identificar la sensibilidad antibiótica en el punto de atención de pacientes en zonas, regiones, establecimientos médicos sin atención 24/7, o en otros tipos de instalaciones donde existe escaso nivel de equipamiento. The technical advantages of the micro device of the invention is that, unlike the micro devices of the state of the art, its structure allows to identify antibiotic sensitivity at the point of care of patients in areas, regions, medical facilities without attention 24 / 7, or in other types of facilities where there is a low level of equipment.
Otra ventaja es que permite la capacidad de identificar la sensibilidad antibiótica en el punto de atención del paciente sin necesidad de derivar la muestra a laboratorios centralizados. Another advantage is that it allows the ability to identify antibiotic sensitivity at the point of patient care without the need to refer the sample to centralized laboratories.
Además, el micro dispositivo es aplicable a la realización de antibiograma por dilución según requerimientos del cliente. In addition, the micro device is applicable to the performance of antibiogram by dilution according to customer requirements.
El micro dispositivo es adaptable a las condiciones epidemiológicas de cada país o región The micro device is adaptable to the epidemiological conditions of each country or region
Es un producto listo para usar - Ready to Use - lo cual facilita su empleo en zonas rurales o donde no existe personal ni equipamiento médico en forma permanente. It is a ready-to-use product - Ready to Use - which facilitates its use in rural areas or where there is no permanent staff or medical equipment.
Los resultados precisos y confiables obtenidos con mayor rapidez que el antibiograma convencional. Posee una mayor facilidad de lectura para interpretación de resultados. Accurate and reliable results obtained faster than the conventional antibiogram. It has a greater ease of reading for interpretation of results.
El micro dispositivo cumple además con certificación ISO 13.485 para dispositivos médicos, lo cual facilita el registro en los países de destino. The micro device also complies with ISO 13.485 certification for medical devices, which facilitates registration in destination countries.
BREVE DESCRIPCIÓN DE LAS FIGURAS BRIEF DESCRIPTION OF THE FIGURES
La figura 1 es una vista de una tapa con perforaciones para micro pocilios de un modelo de dos piezas de un micro dispositivo de acuerdo a una modalidad de la invención. Figure 1 is a view of a cover with perforations for micro wells of a two-piece model of a micro device according to an embodiment of the invention.
La figura 2 es una vista de un sustrato con micro canales de un modelo de dos piezas de un micro dispositivo de acuerdo a una modalidad de la invención. Figure 2 is a view of a substrate with micro channels of a two-piece model of a micro device according to an embodiment of the invention.
La figura 3 es una vista de un micro dispositivo de una pieza de acuerdo a una modalidad de la invención. Figure 3 is a view of a one-piece micro device according to an embodiment of the invention.
La figura 4 es una vista de una tapa con perforaciones para micro pocilios y micro canales de un modelo de dos piezas de un micro dispositivo de acuerdo a una modalidad de la invención. Figure 4 is a view of a cover with perforations for micro wells and micro channels of a two-piece model of a micro device according to an embodiment of the invention.
La figura 5 es una vista de un sustrato con perforaciones para micro pocilios de un modelo de dos piezas de un micro dispositivo de acuerdo a una modalidad de la invención. Figure 5 is a view of a substrate with perforations for micro wells of a two-piece model of a micro device according to an embodiment of the invention.
La figura 6 es un par de vistas de un molde para fabricación de un micro dispositivo de acuerdo a una modalidad de la invención. Figure 6 is a pair of views of a mold for manufacturing a micro device according to an embodiment of the invention.
La figura 7 es un par de vistas de máscara para fabricación de un micro dispositivo de acuerdo a una modalidad de la invención. DESCRIPCIÓN DETALLADA DE LA INVENCIÓN Figure 7 is a pair of mask views for manufacturing a micro device according to an embodiment of the invention. DETAILED DESCRIPTION OF THE INVENTION
La invención describe un micro dispositivo o dispositivo médico (10) tipo lab-on-chip, capaz de identificar la sensibilidad antibiótica en el punto de atención de los pacientes, especialmente en zonas rurales, consultorios, hospitales que no tienen atención 24 / 7, hospitales con escaso nivel del equipamiento, trasatlánticos, entre otros. The invention describes a micro-device or medical device (10) lab-on-chip type, capable of identifying antibiotic sensitivity at the point of care of patients, especially in rural areas, offices, hospitals that have no attention 24/7, hospitals with low level of equipment, ocean liners, among others.
Los micro dispositivos se emplean en pacientes con infecciones del tracto urinario y la muestra a emplear será orina. The micro devices are used in patients with urinary tract infections and the sample to be used will be urine.
El dispositivo (10) tiene geometría de preferencia de tipo circular, de preferencia de 7 a 9 cm de diámetro. Dicho dispositivo (10) es fabricado de preferencia de un polímero de grado médico, olefina cíclica u otro material I. El micro dispositivo (10) cuenta con una microcámara (20) para depositar la muestra. The device (10) has a circular type preference geometry, preferably 7 to 9 cm in diameter. Said device (10) is preferably manufactured from a medical grade polymer, cyclic olefin or other material I. The micro device (10) has a microcamera (20) for depositing the sample.
Desde dicha microcámara (20) salen una pluralidad de microcanales (30), donde cada microcanal (30) difunde a un respectivo micropocillo (40) de preferencia circulares, en el cual se desarrolla el proceso de identificación de la sensibilidad antibiótica. From said microcamera (20) a plurality of microchannels (30) leave, where each microchannel (30) diffuses to a respective circular microwell (40), in which the process of identifying antibiotic sensitivity is developed.
Cada uno de los micropocillos (40) de cada dispositivo (10) contiene un antibiótico, un medio de cultivo y una sustancia cromófora. Para el caso de las infecciones urinarias los antibióticos a emplear corresponden a los de uso rutinario en la práctica médica, dentro de los cuales se pueden utilizar preferentemente Acido pipedimico, Cefalotoxina, Ciprofloxacino, Cotrimozaxol, Gentamicina, Nitrofurantoína, Ampicilina, lo cual no excluye el uso de otros antibióticos De acuerdo a la modalidad preferida de la invención, cada microcanal (30) conecta la microcámara (20) con su respectivo micropocillo (40), configurando una estructura preferentemente de simetría radial. Cada microcanal (30) y cada micropocillo (40) son independientes de los otros, para evitar contaminación cruzada, de modo que la muestra que difunde desde la microcámara debe tener flujo unidireccional. Each of the microwells (40) of each device (10) contains an antibiotic, a culture medium and a chromophore substance. In the case of urinary infections, the antibiotics to be used correspond to those of routine use in medical practice, within which you can preferably use Pipedimic acid, Cephalotoxin, Ciprofloxacin, Cotrimozaxol, Gentamicin, Nitrofurantoin, Ampicillin, which does not exclude use of other antibiotics According to the preferred embodiment of the invention, each microchannel (30) connects the microcamera (20) with its respective microwell (40), forming a structure preferably of radial symmetry. Each microchannel (30) and each microwell (40) are independent of the others, to avoid cross contamination, so that the sample that diffuses from the microcamera must have unidirectional flow.
De acuerdo al diseño de la modalidad preferida de la invención, se considera actuación del flujo basada en capilaridad, con incorporación de pozos a distintos niveles como apoyo al flujo unidireccional. El empleo de capilares, de preferencia entre 300 y 600 micrones de ancho y unos 5 mm de longitud, aporta valores razonables de tiempos de recorrido de los canales y permite su fabricación con las tecnologías disponibles. According to the design of the preferred embodiment of the invention, flow performance based on capillarity is considered, with incorporation of wells at different levels in support of the unidirectional flow. The use of capillaries, preferably between 300 and 600 microns in width and about 5 mm in length, provides reasonable values of channel travel times and allows their manufacture with the available technologies.
Para fabricación de dichos micro dispositivos (10) se puede utilizar una serie de procesos de fabricación. En dichos procesos destaca la utilización de diseños 2DV2 y 3D, así como las tecnologías de fabricación por fotolitografía UV y ataque químico, por estereolitografía láser y por colada en moldes de silicona, puesto que en función del nivel de detalle requerido, de la productividad necesaria o de los materiales de interés, se puede recurrir al empleo de unas u otras. A series of manufacturing processes can be used to manufacture said micro devices (10). In these processes, the use of 2DV2 and 3D designs stands out, as well as the manufacturing technologies for UV photolithography and chemical attack, for laser stereolithography and for casting in silicone molds, since depending on the level of detail required, the productivity required or of the materials of interest, one can resort to the use of one or the other.
En una de las modalidades preferidas de la invención, los diseños de los micro dispositivos (10) presentan una zona circular central para depositar la muestra correspondiente a la microcámara (20) y de la cual surgen carriles radiales o microcanales (30) que conectan con al menos siete u ocho micropocillos (40) externos para reacción. Se han probado diferentes anchos y alturas para los carriles, desde los 300 hasta los 600 micrones y, con diámetros totales de los dispositivos que van de preferencia desde los 10 mm hasta los 40 mm, lo que no limita el us de micro dispositivos de mayor diámetro. In one of the preferred embodiments of the invention, the designs of the micro devices (10) have a central circular zone for depositing the sample corresponding to the microcamera (20) and from which radial or microchannel rails (30) arise that connect with at least seven or eight external microwells (40) for reaction. Different widths and heights have been tested for lanes, from 300 to 600 microns and, with total device diameters preferably ranging from 10 mm to 40 mm, which does not limit the use of larger diameter micro devices.
Existen al menos tres tipos de modalidades de micro dispositivos (10). La primera modalidad incluye una tapa (50) y un sustrato (60), donde dicha tapa (50) posee la perforación para la microcámara (20) y perforaciones para la pluralidad de micropocillos (40) tal como se muestra en la Figura 1 . El sustrato (60) incorpora los microcanales (30), tal como lo muestra la Figura 2. Los micropocillos (40) tienen mayor profundidad para el encapsulamiento de reactivos y para producir efecto anti retorno una vez que cada microcanal (30) se haya vaciado por capilaridad. There are at least three types of micro device modalities (10). The first embodiment includes a lid (50) and a substrate (60), wherein said lid (50) has the perforation for the microcamera (20) and perforations for the plurality of microwells (40) as shown in Figure 1. The substrate (60) incorporates the microchannels (30), as shown in Figure 2. The microwells (40) have greater depth for reagent encapsulation and to produce anti-return effect once each microchannel (30) has been emptied by capillarity.
En una segunda modalidad, el micro dispositivo (10) se conforma de una única pieza con microcanales (30) internos que conectan la microcámara (20) con cada micropocillo (40) tal como lo muestra la Figura 3, para aprovechar en toda su potencia las tecnologías de fabricación aditiva. In a second embodiment, the micro device (10) is made up of a single piece with internal microchannels (30) that connect the microcamera (20) with each microwell (40) as shown in Figure 3, to take full advantage Additive manufacturing technologies.
En una tercera modalidad de la invención, el diseño del micro dispositivo (10) está orientado a un encapsulamiento mejorado de los reactivos, pensando en el empleo adicional de una lámina adhesiva de doble cara intermedia que se perforaría en el punto de atención al paciente previo al uso del sistema. En esta modalidad, el micro dispositivo (10) comprende una tapa (70) y un sustrato (80), donde dicha tapa (70) comprende las perforaciones para la microcámara (20), para la pluralidad de microcanales (30) y para los micropocillos (40) tal como se muestra en la Figura 4, y dicho sustrato (80) comprende perforaciones para los micropocillos (40), tal como se muestra en la Figura 5. In a third embodiment of the invention, the design of the micro device (10) is oriented to an improved encapsulation of the reagents, considering the additional use of an intermediate double-sided adhesive sheet that would be perforated at the point of previous patient care. to the use of the system. In this embodiment, the micro device (10) comprises a cover (70) and a substrate (80), wherein said cover (70) comprises perforations for the microcamera (20), for the plurality of microchannels (30) and for the microwells (40) as shown in Figure 4, and said substrate (80) comprises perforations for microwells (40), as shown in Figure 5.

Claims

REIVINDICACIONES
1 . - Micro dispositivo (10) tipo lab-on-chip, capaz de identificar la sensibilidad antibiótica en el punto de atención de los pacientes, especialmente en zonas rurales, consultorios, hospitales que no tiene atención 24 / 7, hospitales con escaso nivel del equipamiento, entre otros, CARACTERIZADO porque dicho micro dispositivo (10) tiene geometría de preferencia de tipo circular, y comprende una microcámara (20) en el centro del micro dispositivo (10) para depositar la muestra, donde desde dicha microcámara (20) salen una pluralidad de microcanales (30), y en donde cada microcanal (30) difunde la muestra a un respectivo micropocillo (40), en el cual se desarrolla el proceso de identificación de la sensibilidad antibiótica. one . - Micro-device (10) lab-on-chip type, capable of identifying antibiotic sensitivity at the point of care of patients, especially in rural areas, offices, hospitals that do not have 24/7 care, hospitals with low level of equipment , among others, CHARACTERIZED because said micro device (10) has circular geometry of preference, and comprises a micro camera (20) in the center of the micro device (10) for depositing the sample, where from said micro camera (20) a plurality of microchannels (30), and wherein each microchannel (30) broadcasts the sample to a respective microwell (40), in which the process of identifying antibiotic sensitivity is developed.
2. - Micro dispositivo (10) de acuerdo a la reivindicación 1 CARACTERIZADO porque tiene preferentemente un diámetro de 7 a 9 cm. 2. - Micro device (10) according to claim 1 CHARACTERIZED because it preferably has a diameter of 7 to 9 cm.
3. - Micro dispositivo (10) de acuerdo a cualquiera de las reivindicaciones anteriores CARACTERIZADO porque es fabricado de preferencia de polímero de grado médico, olefina cíclica u otro material similar. 3. - Micro device (10) according to any of the preceding claims CHARACTERIZED because it is preferably manufactured from medical grade polymer, cyclic olefin or other similar material.
4. - Micro dispositivo (10) de acuerdo a cualquiera de las reivindicaciones anteriores CARACTERIZADO porque cada microcanal (30) conecta dicha microcámara (20) con su respectivo micropocillo (40), configurando una estructura preferentemente de simetría radial 4. - Micro device (10) according to any of the preceding claims CHARACTERIZED because each microchannel (30) connects said microcamera (20) with its respective microwell (40), forming a structure preferably of radial symmetry
5. - Micro dispositivo (10) de acuerdo a cualquiera de las reivindicaciones anteriores CARACTERIZADO porque cada microcanal (30) y cada micropocillo (40) son independientes de los otros, para evitar contaminación cruzada, de modo que la muestra que difunde desde la microcámara tiene un flujo unidireccional. 5. - Micro device (10) according to any of the preceding claims CHARACTERIZED because each microchannel (30) and each microwell (40) are independent of the others, to avoid cross contamination, so that the sample that diffuses from the microcamera It has a unidirectional flow.
PCT/IB2013/059726 2013-10-28 2013-10-28 Microdevice of the lab-on-a-chip type, for identifying antibiotic sensitivity in the care point of the patient WO2015063540A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002010713A2 (en) * 2000-08-02 2002-02-07 Honeywell International Inc. Portable flow cytometer
US20050136685A1 (en) * 2003-12-19 2005-06-23 Kei Takenaka Chips, and apparatus and method for reaction analysis
WO2007005973A2 (en) * 2005-07-01 2007-01-11 Honeywell International, Inc. A microfluidic card for rbc analysis
WO2012011810A1 (en) * 2010-07-22 2012-01-26 Stichting Voor De Technische Wetenschappen Lab-on-a-chip device, for instance for use of the analysis of semen

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002010713A2 (en) * 2000-08-02 2002-02-07 Honeywell International Inc. Portable flow cytometer
US20050136685A1 (en) * 2003-12-19 2005-06-23 Kei Takenaka Chips, and apparatus and method for reaction analysis
WO2007005973A2 (en) * 2005-07-01 2007-01-11 Honeywell International, Inc. A microfluidic card for rbc analysis
WO2012011810A1 (en) * 2010-07-22 2012-01-26 Stichting Voor De Technische Wetenschappen Lab-on-a-chip device, for instance for use of the analysis of semen

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