WO2019103743A1 - Dispositifs microfluidiques pour coagulation sanguine - Google Patents
Dispositifs microfluidiques pour coagulation sanguine Download PDFInfo
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- WO2019103743A1 WO2019103743A1 PCT/US2017/063102 US2017063102W WO2019103743A1 WO 2019103743 A1 WO2019103743 A1 WO 2019103743A1 US 2017063102 W US2017063102 W US 2017063102W WO 2019103743 A1 WO2019103743 A1 WO 2019103743A1
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- lid
- microchip
- discrete
- microfluidic
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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
- B01L3/502—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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/4905—Determining clotting time of blood
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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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
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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
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0825—Test strips
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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
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
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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
- 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
- Coagulation testing can be used to monitor patients taking oral anticoagulants in response to a variety of medical conditions (e.g. stroke, pulmonary embolism, etc.). Coagulation testing can also be generally performed in clinical diagnostics of the hemostasis system. While there are a number of different coagulation tests that can be performed, the coagulation testing is generally categorized into global and local tests. Global tests are intended to characterize the general state of the blood coagulation system. Local tests are intended to characterize separate components of the blood coagulation system cascade.
- FIG. 1A is a side cross-sectional view of an example microfluidic device in accordance with the present disclosure.
- FIG. 1 B is a top cross-sectional view of an example microfluidic device in accordance with the present disclosure.
- FIG. 1 C is a top plan view of an example microfluidic device in accordance with the present disclosure.
- FIG. 2 is a top cross-sectional view of an example microfluidic device in accordance with the present disclosure.
- Microfluidic devices can be used for a variety of applications, including biotechnology, drug screening, clinical diagnostic testing, etc.
- One such application of a microfluidic device can be blood coagulation testing.
- coagulation testing can be used to monitor patients taking oral anticoagulants in response to a variety of medical conditions (e.g. stroke, pulmonary embolism, etc.), for example, and can be used as an indicator of patient health.
- medical conditions e.g. stroke, pulmonary embolism, etc.
- patients on these medications generally participate in routine clinical testing, which can be expensive and inconvenient if performed in a centralized lab.
- it can be advantageous to provide an at-home test kit that can be relatively inexpensive and user friendly.
- a microfluidic device can include a substrate, a lid mounted to the substrate, and a microchip mounted to the substrate.
- the lid and substrate can form a discrete microfluidic chamber between structures including an interior surface of the lid and a portion of the substrate.
- the lid can also include an inlet and a vent positioned relative to one another to facilitate loading of a fluid to the discrete microfluidic chamber via capillary action.
- a portion of the microchip can include a blood coagulation component positioned within the discrete microfluidic chamber.
- a microfluidic device can include a substrate, a lid mounted to the substrate, and a microchip mounted to the substrate.
- the lid and substrate can form a discrete microfluidic chamber between structures including an interior surface of the lid and a portion of the substrate.
- the lid can also include an inlet and a vent positioned relative to one another to facilitate loading of a fluid to the discrete microfluidic chamber via capillary action.
- a portion of the microchip can include a blood coagulation component positioned within the discrete microfluidic chamber.
- the microchip can include a temperature regulator.
- a microfluidic device can include a substrate, a lid mounted to the substrate, and a microchip mounted to the substrate.
- the lid and substrate can form a discrete microfluidic chamber between structures including an interior surface of the lid and a portion of the substrate.
- the lid can also include an inlet and a vent positioned relative to one another to facilitate loading of a fluid to the discrete microfluidic chamber via capillary action.
- the discrete microfluidic chamber can have a volume from 1 nl to 100 pi.
- a portion of the microchip can include a blood coagulation component positioned within the discrete microfluidic chamber.
- the microchip can be an elongated microchip having a width to length aspect ratio from 1 :10 to 1 :150.
- the blood coagulation component can include a sensor, a temperature regulator, or a combination thereof.
- the sensor can include an optical sensor, a temperature sensor, or a combination thereof.
- the temperature regulator can include a resistive heater, a peltier heater, a thermal sense resistor, or a combination thereof.
- the temperature regulator can also act as a temperature sensor.
- the lid can form multiple discrete microfluidic chambers between portions of the interior surface of the lid and corresponding portions of the microchip and substrate.
- the discrete microfluidic chamber can have a volume of from 1 nl to 100 mI.
- the substrate can include a material selected from a metal, glass, silicon, silicon dioxide, a ceramic material, a polymer material, or a combination thereof.
- the lid on the other hand, can include a material selected from glass, quartz, polymer, amorphous polymer, or a combination thereof.
- a coagulation additive can be disposed within the discrete microfluidic chamber.
- FIGs. 1A-1 C Reference will now be made to FIGs. 1A-1 C to help describe some of the general features of the microfluidic device. It is noted that the microfluidic devices depicted in the present figures are not drawn to scale and are not intended to be interpreted as such. The representations of the microfluidic devices in the figures are merely intended to facilitate the description and presentation of the microfluidic devices disclosed herein.
- FIGs. 1A-1 C depict an example of a microfluidic device 100 having a substrate 105 with a microchip 1 10 mounted thereto.
- the microchip can include a blood coagulation component 140.
- a lid 120 can be mounted to the substrate, which can form a discrete microfluidic chamber 130 between structures including an interior surface 121 of the lid a portion of the substrate.
- the lid can include an inlet 132 and a vent 134 positioned relative to one another to facilitate loading of a fluid to the discrete microfluidic chamber via capillary action.
- the substrate can include or be made of a material such as a metal, glass, silicon, silicon dioxide, a ceramic material (e.g. alumina, aluminum borosilicate, etc.), a polymer material (e.g. polyethylene, polypropylene, polycarbonate, poly(methyl methacrylate), epoxy molding compound, polyamide, liquid crystal polymer (LCP), polyphenylene sulfide, polydimethylsiloxane, etc.), the like, or a combination thereof.
- the substrate can typically have any suitable dimensions for a given application so long as the microchip and lid structure can be effectively mounted thereto.
- the substrate and the lid can be architecturally compatible to form a complete seal at their interface.
- the microchip generally has an aspect ratio of from 1 : 10 to 1 : 150 width 1 14 to length 116.
- the elongated microchip can have an aspect ratio of from 1 :1.1 to 1 :50 width to length.
- the elongated microchip can have an aspect ratio of from 1 :2 to 1 :25 width to length.
- the microchip is not an elongated microchip such that the microchip can be substantially square, circular, or otherwise fall outside of the aspect ratio described above.
- the microchip can be made of a variety of materials.
- the microchip includes or is made of silicon.
- the microchip can include or be made of glass, quartz, or ceramic.
- the microchip can include a wire, a trace, a network of wires, a network of traces, an electrode or the like embedded in or proud of the substrate.
- the microchip can include a variety of functional components, such as heaters, sensors, electromagnetic radiation sources, fluid actuators, mixers, bubblers, fluid pumps, the like, or combinations thereof, which can vary depending on the intended application of the microfluidic device.
- the microchip 1 10 can be substantially disposed above the substrate 105. However, in some examples, the microchip, or a portion thereof, can be embedded within the substrate such that a lesser portion of the microchip extends above the substrate. In some further examples, the microchip does not extend above the substrate, but a portion (e.g. a single surface or portion of a surface) of the microchip including the blood coagulation component 140 can be exposed to interact with a fluid introduced into the discrete microfluidic chamber 130.
- a portion of the microchip 1 10 can be positioned within the discrete microfluidic chamber 130 (e.g. an internal portion) and a portion or portions of the microchip can be positioned outside of the discrete microfluidic chamber (e.g. an external portion).
- the discrete microfluidic chamber 130 e.g. an internal portion
- a portion or portions of the microchip can be positioned outside of the discrete microfluidic chamber (e.g. an external portion).
- not all exposed surfaces e.g. surfaces, or portions of surfaces, not directly mounted to the substrate 105
- each of the exposed surfaces of the microchip can be disposed within the discrete
- microfluidic chamber (not shown).
- the microchip can be oriented in any suitable way so that the blood coagulation component 140 can be positioned within the discrete microfluidic chamber. This can allow a fluid introduced into the discrete microfluidic chamber to interface with, approximate, or otherwise interact with the blood coagulation component.
- the microfluidic device can include multiple microchips including respective blood coagulation components.
- the plurality of microchips, or portions thereof can be positioned within a common discrete microfluidic chamber, within respective separate microfluidic chambers, or positioned in multiples within separate microfluidic chambers.
- the discrete microfluidic chamber 130 can be formed between structures including an interior surface 121 of the lid 120 and portion of the substrate 105.
- the lid can have a variety of dimensions and geometries depending on the desired configuration of the discrete microfluidic chamber and the particular blood coagulation test intended to be performed with the device 100.
- the lid can have a rectangular shape.
- Other geometries can also be employed as desired for particular applications, such as elliptical, circular, arcuate, polygonal, trapezoidal, and other desirable geometries.
- the lid can be shaped to house a portion of the microchip 1 10 that includes the blood coagulation component for monitoring or manipulating a blood sample.
- the lid can generally form a fluid seal against the substrate 105 so that fluid can only enter and exit the discrete microfluidic chamber through designated inlets and outlets, such as inlet 132 and outlet/vent 134. In some examples, where a portion or portions of the microchip extend out of the discrete microfluidic chamber, the lid can also form a fluid seal against a segment or segments of the microchip.
- the positioning of the inlet 132 and outlet/vent 134 is not particularly limited.
- the inlet and vent can be positioned relative to one another to facilitate introduction of a fluid into the discrete microfluidic chamber 130 via capillary action.
- the inlet and vent can be positioned relative to one another to approximate a fluid to or interface a fluid with the blood coagulation component 140 to facilitate fluid monitoring and/or manipulation of a blood sample.
- the lid can be formed of a variety of different materials. Non-limiting examples can include glass, quartz, a metal, a polymer, an amorphous polymer, or other suitable materials. Non-limiting examples of polymers can include polydimethylsiloxane (PDMS), cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polyethylene terephthalate (PET), the like, or a combination thereof. In some examples, the lid can include or be made of a transparent or translucent material such as glass, quartz, polycarbonate, trivex, COC, the like, or a combination thereof.
- a transparent or translucent material such as glass, quartz, polycarbonate, trivex, COC, the like, or a combination thereof.
- the lid can include or be made of a non-translucent material, such as silicon, a metal, the like, or a combination thereof.
- the material used to manufacture the lid can be doped with a dopant to enhance thermal performance, optical performance, chemical performance, the like, or a combination thereof.
- dopants can include erbium, AIO x , TaO x , or the like.
- the lid can be formed in a variety of ways. Non-limiting examples can include injection molding, cast molding, compression molding, etching, cutting, melting, drilling, routing, the like, or a combination thereof.
- the lid can be used to form a single discrete microfluidic chamber or multiple discrete microfluidic chambers.
- FIG. 2 illustrates a microfluidic device 200 having a substrate 205 with a microchip 210 mounted thereto.
- a lid 220 can also be mounted to the substrate.
- the lid has been shaped to form multiple discrete microfluidic chambers 230A, 230B, 230C between respective portions of the interior surface of the lid and corresponding portions of the substrate.
- Individual blood coagulation components 240A, 240B, 240C can be associated with respective discrete microfluidic chambers.
- the discrete microfluidic chambers can be oriented in a direction transverse to the microchip.
- the discrete microfluidic chambers can be oriented in any suitable orientation relative to the microchip.
- the same number and orientation of discrete microfluidic chambers can be formed by mounting multiple lids to the substrate. Individual lids can form a single discrete microfluidic chamber or multiple microfluidic chambers.
- the internal volume of the discrete microfluidic chamber can vary somewhat.
- the discrete microfluidic chamber can typically have a volume of from about 1 nl to about 100 pi.
- the discrete microfluidic chamber can have a volume of from 100 nl to 1 mI.
- the discrete microfluidic chamber can have a volume of from about 1 mI to about 10 mI.
- the discrete microfluidic chamber can have a volume of from about 500 nl to about 6 mI.
- the combined volume of each of the discrete microfluidic chambers can typically fall within the ranges recited above. Individual chamber volumes can be calculated based on the proportion of the combined volume provided by any given chamber. However, for some
- the internal volume of the discrete microfluidic chamber(s) may vary somewhat outside of the ranges disclosed herein.
- the blood coagulation component 140 is illustrated as positioned at an upper surface of the microchip 1 10.
- the blood coagulation component can be positioned at any suitable location of the microchip, or portion of the microchip disposed within the discrete microfluidic chamber 130.
- FIGs. 1A-1 C illustrate, for example, a single blood coagulation component.
- the microchip can include any suitable number of blood coagulation components, which can be positioned in any suitable location, orientation, pattern, or configuration.
- the blood coagulation component can include a sensor, a temperature regulator, or a combination thereof.
- sensors can be used, such as an optical sensor, a thermal sensor, or a combination thereof.
- Optical sensors can include a photodiode, a phototransistor, the like, or a combination thereof.
- Thermal sensors can include a thermocouple, a thermistor, a thermal sense resistor, the like, or a combination thereof.
- a variety of temperature regulators can likewise be used. Non-limiting examples can include a resistive heater, a peltier heater, the like, or a combination thereof.
- the blood coagulation component can include a temperature regulator that can also function as a sensor, such as in the case of a thermal sense resistor (TSR), for example.
- TSR thermal sense resistor
- a TSR can both add heat to the discrete microfluidic chamber and measure a temperature within the microfluidic chamber.
- a microfluidic device can be prepared by mounting a silicon microchip to a substrate.
- a glass lid structure can be mounted to the substrate to cover a majority of the silicon microchip and form a discrete microfluidic channel about the silicon microchip.
- the silicon microchip can include a thermal sense resistor for both temperature regulation and temperature sensing of a fluid sample.
- An inlet and vent can be formed at opposite ends of the lid structure to facilitate loading of the discrete microfluidic channel via capillary action.
- the outer dimensions of the lid can be from about 1 mm to about 3 mm (e.g. about 2mm) in width, from about 0.5 mm to about 1 .5 mm (e.g.
- the inner dimensions of the lid can be from about 0.1 mm to about 1 .5 mm (e.g. about 0.6 mm) in width, from 0.1 mm to about 1.0 mm (e.g. about 0.4 mm) in height, and from about 10 mm to about 30 mm (e.g. about 20 mm) in length.
- the lid can form a single chamber having an internal volume of about 1 pi to about 6 pi (e.g. about 4 mI).
- the present disclosure also describes a method of detecting blood coagulation.
- the method can include loading a volume of a blood sample into a discrete microfluidic chamber of a microfluidic device via capillary action.
- the microfluidic device can include a substrate and a microchip mounted to the substrate.
- the microchip can include a blood coagulation component.
- a lid can be mounted to the substrate and form the discrete microfluidic chamber between structures including an interior surface of the lid and a portion of the substrate.
- the lid can also include an inlet and a vent positioned relative to one another to facilitate loading of a fluid to the discrete microfluidic chamber via capillary action.
- a portion of the microchip including the blood coagulation component can be positioned within the discrete microfluidic chamber.
- the method can also include detecting coagulation of the blood sample introduced to the discrete microfluidic chamber.
- the blood sample can be whole blood.
- the plasma can be platelet-free plasma, platelet-poor plasma, platelet-rich plasma, the like, or a combination thereof.
- the blood sample can include both whole blood and plasma.
- the microfluidic device can include multiple discrete microfluidic chambers, which can be used to evaluate a common blood sample, or multiple different blood samples, such as blood samples from different sources, whole blood and plasma samples from a common source, or the like.
- the volume the blood sample introduced into a discrete microfluidic chamber can vary depending on the size of the discrete microfluidic chamber, the number of microfluidic chambers employed, the specific blood coagulation test being employed, etc. In some specific examples, the volume of the blood sample can be an amount from about 1 nl to about 100 pi. In other examples, the volume of the blood sample can be an amount from about 100 nl to about 5 mI. In some examples, the volume of blood introduced into the discrete microfluidic chamber can be obtained from a lancet puncture, a finger prick, or the like, without a venous draw, or equivalent.
- coagulation of the blood sample can be detected in a variety of ways.
- blood coagulation can be optically detected This can be done in a number of ways.
- the blood sample can be loaded to the discrete microfluidic chamber via capillary action, which can allow the blood sample to continue progression through the discrete microfluidic chamber from the inlet toward the vent via capillary action.
- the viscosity of the blood sample can increase and impede the flow of the blood sample through the discrete microfluidic chamber.
- the progress of the blood sample through the discrete microfluidic chamber can be optically monitored using an optical sensor. Accordingly, blood coagulation of the blood sample can be measured as a function of time, a function of distance travelled through the discrete microfluidic chamber during the testing period, etc., or a combination thereof.
- the sensor employed to optically detect blood coagulation can be an external sensor (e.g. a sensor not included on the microchip), an internal sensor (e.g. a sensor included on the microchip), or a combination thereof.
- the optical sensor can be or include an external sensor.
- the optical sensor can be or include an internal sensor.
- the internal sensor can include multiple optical sensors spaced along a portion of the microchip positioned within the discrete microfluidic chamber.
- blood coagulation can be detected thermally.
- a blood sample can be loaded into a discrete microfluidic chamber via capillary action.
- the blood sample can progress through the discrete microfluidic chamber from the inlet toward the vent via capillary action.
- TSR thermal sense resistor
- a voltage can be applied to the TSR to pulse the sample with heat.
- the increase and decrease in temperature in the microchip and/or the blood sample can be measured to generate a thermal profile.
- the thermal profile can change as coagulation proceeds and can be used to determine when clotting occurs.
- a temperature ramp can be initiated when testing begins and the amount of input heat used to maintain the temperature ramp can be monitored as blood coagulation proceeds to generate a thermal profile. This thermal profile can then be used to determine when clotting occurs.
- Other similar methods can be used to thermally detect blood coagulation.
- the sensor employed to thermally detect blood coagulation can be an external sensor (e.g. a sensor not included on the microchip), an internal sensor (e.g. a sensor included on the microchip), or a combination thereof.
- the thermal sensor can be or include an external sensor.
- the thermal sensor can be or include an internal sensor.
- the internal sensor can include multiple thermal sensors spaced along a portion of the microchip positioned within the discrete microfluidic chamber.
- the internal thermal sensor can be a thermal sensor that extends along a length (e.g.
- blood coagulation can be detected using a combination of optical and thermal sensing.
- both optical and thermal sensors can be included on the microchip.
- an optical sensor can be an external sensor and the thermal sensor can be an internal sensor.
- the optical sensor can be an internal sensor and the thermal sensor can be an external sensor.
- the optical sensor and the thermal sensor can be external sensors.
- the optical sensor can include a combination of internal and external sensors.
- the thermal sensor can include a combination of internal and external sensors.
- detecting blood coagulation can also include regulating a temperature of the blood sample.
- the temperature of the blood sample can be regulated using an external temperature regulator (e.g. a temperature regulator not included on the microchip), an internal temperature regulator (e.g. a temperature regulator included on the microchip), or a combination thereof.
- Temperature regulators can include heat transfer fluids, convective heating, resistive heating, peltier heaters, the like, or a combination thereof.
- detecting blood coagulation can include regulating a temperature of the blood sample using an external temperature regulator.
- detecting blood coagulation can include regulating a temperature of the blood sample using an internal temperature regulator.
- detecting blood coagulation can include introducing a coagulation additive to the discrete microfluidic chamber.
- the coagulation additive can be added prior to loading the blood sample.
- the coagulation additive can be added after the blood sample.
- the coagulation additive can include a reagent, a tissue factor, silica, or a combination thereof.
- one or more surfaces within the discrete microfluidic chamber can include or be made of glass, silica, or other coagulation initiating surfaces. In some examples, where a coagulation initiating surface can be employed, other coagulation additives may not be needed.
- the present disclosure also describes a method of manufacturing a microfluidic device.
- the method can include mounting a microchip to a substrate.
- the microchip can include a blood coagulation component.
- a lid can also be mounted to the substrate to form a discrete microfluidic chamber between structures including an interior surface of the lid and a portion of the substrate.
- the lid can include an inlet and a vent positioned relative to one another to facilitate loading of a fluid to the discrete microfluidic chamber via capillary action.
- a portion of the microchip including the blood coagulation component can be positioned within the discrete microfluidic chamber.
- the microchip can be mounted to the substrate in any suitable way, such as using wire bonding, die bonding, flip chip mounting, surface mount interconnects, the like, or a combination thereof.
- the lid can also be mounted to the substrate in a variety of ways. Generally, any mounting process that can form a fluid seal between the lid and the substrate can be used. This can prepare a discrete microfluidic chamber that only permits a fluid to enter and exit the chamber at designated inlet and outlet sites.
- the mounting the lid to the substrate can be performed by adhering the lid to the substrate via an adhesive.
- the adhesive can be a curable adhesive.
- mounting can include curing the adhesive via electromagnetic radiation, heat, chemical agents, the like, or a combination thereof.
- suitable adhesives can include epoxy adhesives, acrylic adhesives, the like, or a combination thereof.
- the lid can be mounted to the substrate via laser welding, ultrasonic welding, thermosonic welding, the like, or a combination thereof to mount the lid directly to the substrate.
- a coagulation additive can be loaded into the discrete microfluidic chamber during the manufacturing process. In some examples, this can be done by coating, drying, freeze-drying, or otherwise loading the coagulation additive to the discrete microfluidic chamber during manufacturing. Where this is the case, additional coagulation additives may not need to be added later. However, in some cases, it can be desirable to pre-load the discrete microfluidic chamber with specific coagulation additives, while separately adding others at a later time, such as the time of coagulation testing.
- the term“about” is used to provide flexibility to a numerical range endpoint by providing that a given value may be“a little above” or“a little below” the endpoint.
- the degree of flexibility of this term can be dictated by the particular variable and can be determined based on experience and the associated description herein.
- a weight ratio range of about 1 wt% to about 20 wt% should be interpreted to include not only the explicitly recited limits of 1 wt% and about 20 wt%, but also to include individual weights such as 2 wt%, 1 1 wt%, 14 wt%, and sub-ranges such as 10 wt% to 20 wt%, 5 wt% to 15 wt%, etc.
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Abstract
La présente invention concerne des dispositifs microfluidiques pour la coagulation sanguine. Le dispositif microfluidique peut comprendre un substrat, un couvercle monté sur le substrat, et une micropuce montée sur le substrat. Le couvercle et le substrat peuvent former une chambre microfluidique discrète entre des structures comprenant une surface intérieure du couvercle et une partie du substrat. Le couvercle peut également comprendre une entrée et un évent positionnés l'un par rapport à l'autre pour faciliter le chargement d'un fluide dans la chambre microfluidique discrète par action capillaire. Une partie de la micropuce peut comprendre un composant de coagulation sanguine positionné à l'intérieur de la chambre microfluidique discrète.
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CN114054109B (zh) * | 2021-11-08 | 2022-12-27 | 北京化工大学 | 基于导电弹性体材料的血液凝固检测微流控芯片 |
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