ABSTRACT
Abstract
The present disclosure relates to a fluid analyzing device that includes a sensing device for analyzing a fluid sample. The sensing device includes a microchip configured for sensing the fluid sample, and a closed micro-fluidic component for propagating the fluid sample to the microchip. The fluid sample can be provided to the micro-fluidic component via an inlet of the fluid analyzing device. And a vacuum compartment, which is air-tight connected to the sensing device, can create in the micro-fluidic component a suction force suitable for propagating the fluid sample through the micro-fluidic component.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application is a divisional of U.S. application Ser. No. 15/529,441, filed on May 24, 2017, which is a 35 U.S.C. 371 National Application of PCT/EP2015/077412 filed Nov. 24, 2015, which claims priority to European Patent Application No. 14194854.7 filed on Nov. 26, 2014, the contents of each of which are hereby incorporated by reference.
TECHNICAL FIELD
The present disclosure relates to medical devices for fluid analysis. In particular, the present disclosure is related to compact devices, e.g., medical devices, for the analysis of a fluid sample. In particular, the present disclosure is related to fully integrated devices, such as lab-on-a-chip devices, for the analysis of bodily fluid samples.
BACKGROUND
A disadvantage of conventional point-of-care devices for the analysis of blood is their size which depends on the different components needed to perform analysis of blood. In these devices, external pumps are part of the point of care instrument. In some devices, miniature scale pumps are used to propagate a sample through the fluidic channels of the device. The use of pumps increases the size and cost of the device which makes them less suitable for usage as a disposable device. Current disposable devices are typically inserted in expensive read-out instruments, with many non-disposable electronic or optical components to detect the biochemical reactions taking place in the disposable device. Another disadvantage of state of the art point of care devices is their fabrication cost.
Other state of the art devices are lateral flow test strips. These test strips are usually fabricated from cellulose which does not allow precise control of the flow of a fluid sample propagating through the test strips, which can limit the applicability of these devices.
There is a need for a low-cost, easy to use, disposable, compact device for the fully integrated analysis of a fluid sample.
SUMMARY
It is an object of embodiments of the present disclosure to provide an easy to use device and method for analyzing a fluid sample.
It is an advantage of embodiments of the present disclosure that, at least for some actions, connecting the device to a separate fluid propagating element such as a pumping means can be avoided.
It is an advantage of embodiments of the present disclosure to provide compact devices for analyzing fluid samples as well as corresponding methods for analyzing fluid samples.
It is an advantage of embodiments of the present disclosure that low-cost devices for analyzing fluid samples can be provided, whereby such low-cost devices can, for example, be disposable.
This objective is accomplished by a method and device according to embodiments of the present disclosure.
According to an aspect of the disclosure, a fluid analyzing device is presented. The fluid analyzing device comprises: a sensing device for analyzing a fluid sample, the sensing device comprising: a microchip configured for sensing the fluid sample and a closed micro-fluidic component for propagating the fluid sample to the microchip. The fluid analyzing device also includes a vacuum compartment air-tight connected to the sensing device and adapted for creating a suction force in the micro-fluidic component by opening the vacuum compartment, the suction force being suitable for propagating the fluid sample through the micro-fluidic component. Further the fluid analyzing device includes an inlet for providing the fluid sample to the micro-fluidic component. Hence, the micro-fluidic component is closed off from the inlet for providing the fluid sample. The sensing device may be defined as a medical device suitable for performing an analysis of a fluid sample, e.g., bodily fluid samples.
According to an embodiment of the disclosure, the vacuum compartment encloses a volume at lower pressure than atmospheric pressure, hence creating the suction force in the micro-fluidic component by opening the vacuum compartment. Vacuum thereby means that the pressure is lower than atmospheric pressure.
According to an embodiment of the disclosure, the fluid analyzing device further comprises a package comprising: the sensing device, the vacuum compartment, and the inlet. The sensing device and the vacuum compartment are encapsulated by the package. The inlet is located in the package, e.g., in a wall of the package, and is connected to the micro-fluidic component such that a fluid sample may be provided to the micro-fluidic component.
According to an embodiment of the disclosure, the vacuum compartment comprises a sacrificial element adapted to open the vacuum compartment towards the micro-fluidic component when the element is destructed.
According to an embodiment of the disclosure, the fluid analyzing device further comprises a movable structure for destructing the sacrificial element. The movable structure may be located in the package. Alternatively, the movable structure may be part of the vacuum compartment.
According to an embodiment of the disclosure, the movable structure is a movable puncture device adapted to destruct the sacrificial element when actuated from outside the package.
According to an embodiment of the disclosure, the sacrificial element comprises a heating resistor positioned such that the sacrificial element is destructed by heating.
According to an embodiment of the disclosure, the heating resistor is positioned in or on the sacrificial element. According to an embodiment of the disclosure, the heating resistor is positioned on a substrate comprising the micro-fluidic component. The heating resistor may be in contact with the sacrificial element.
According to an embodiment of the disclosure, the sacrificial element is solvent-dissolvable. The fluid analyzing device further comprises a solvent compartment containing a solvent. The solvent compartment is configured to release the solvent to the sacrificial element when the fluid sample is provided in the micro-fluidic component. By dissolving the sacrificial element by the released solvent, the vacuum compartment is opened.
According to an embodiment of the disclosure, the fluid analyzing device further comprises a fluid detector positioned to detect the fluid sample when provided in the micro-fluidic component. When the fluid sample is detected, the vacuum compartment is configured to open.
Additionally, the fluid analyzing device also may comprise features of the sensing device described below.
According to an aspect of the disclosure, a method for sensing a fluid sample is presented, comprising: providing a fluid analyzing device; providing a fluid sample to the micro-fluidic component via the inlet for providing the fluid sample to the micro-fluidic component; thereafter propagating the fluid sample through the micro-fluidic component by opening the vacuum compartment to create a pressure difference between the vacuum compartment and the micro-fluidic component; and performing sensing on the fluid sample using the sensing device.
According to an embodiment of the disclosure, the method for sensing a fluid sample further comprises detecting a fluid sample provided to the micro-fluidic component, and wherein the vacuum compartment is opened when the fluid sample is detected.
According to an aspect of the invention, the present disclosure relates to a sensing device for analyzing a fluid sample. The sensing device comprises: a fluidic substrate comprising a micro-fluidic component embedded in the fluidic substrate, where the fluidic substrate is configured to propagate a fluid sample via capillary force through the micro-fluidic component. The sensing device also includes a means connected to the micro-fluidic component for providing a fluid sample; a lid attached to the fluidic substrate thereby at least partly covering the fluidic substrate and at least partly closing the micro-fluidic component. The fluidic substrate is a silicon fluidic substrate and the lid is a microchip (e.g., a CMOS chip).
According to embodiments of the present disclosure, at least a part of the lid is in contact with the fluid sample when the fluid sample is present in the sensing device.
According to embodiments of the present disclosure, the lid comprises a transistor layer, the transistor layer being electrically connected at least one electrical component, the electrical component being at least one of the following: biosensing circuitry, electrodes for sensing purposes, electrodes for fluid manipulation purposes, circuitry for data communication purposes, circuitry for wireless data communication purposes, temperature sensors, heater electrodes for temperature control and fluid sensors and electrodes for fluidic viscosity control, imaging components, e.g., lensfree imaging components. These electrical components may be present on the lid, hence on the microchip. In an embodiment, the transistor layer and the electrical components are integrated in a single microchip.
According to embodiments of the present disclosure, the means for providing a fluid sample is a needle fabricated from a semiconductor, e.g., silicon, and comprises an inner fluidic channel connected to the micro-fluidic component. The needle is a protruding portion of the fluidic substrate and positioned to penetrate skin tissue when pressed against the skin tissue.
According to embodiments of the present disclosure, the fluidic substrate comprises a cut-out and the needle is positioned in the cut-out.
According to embodiments of the present disclosure, the fluidic substrate comprises a protection structure for protecting the needle, the protection structure being removably attached to the fluidic substrate.
According to embodiments of the present disclosure, the means for providing a fluid sample is an inlet. A sample drop may be inserted into the microfluidic component by means of capillary suction, or by other suitable means. The microfluidic component may comprise different fluidic compartments, for instance for multi-omic analysis. The different microfluidic compartments can have the same or different depths. The different microfluidic compartments may be separated by valves that may be actuated in any suitable way, for instance by fluidic forces or by electricity. Electrodes for actuation may be contained on the fluidic substrate or on the lid.
According to embodiments of the present disclosure, the fluidic substrate or the lid may further comprise at least one optical waveguide to allow optical excitation and sensing of the fluid sample when present in the sensing device. The fluidic substrate or the lid may also comprise filters for rejecting optical excitation from emission to measure a fluorescent signal. The fluidic substrate or the lid may comprise multispectral filters for measuring fluorescent signals with multiple colors. The fluidic substrate or the lid may comprise an optical waveguide and/or a pinhole to irradiate the sample for performing lensfree microscopy.
According to embodiments of the present disclosure, the fluidic substrate or the lid comprises at least one through-hole for application of a biochemical reagent to at least one region of the micro-fluidic component or to at least one region of the lid.
According to embodiments of the present disclosure, the lid is bonded to the fluidic substrate using a lithographically patterned polymer.
According to embodiments of the present disclosure, the sensing device may further comprise metal contacts electrically connected to the microchip for detecting electrical signals generated by the fluid and captured by measurement systems in the lid. According to embodiments of the present disclosure, the lid of the sensing device may further comprise CMOS active pixels for detecting optical signals from the fluid.
According to embodiments of the present disclosure, the fluidic substrate comprises a cut-out and the needle is positioned in the cut-out.
According to embodiments of the present disclosure, the fluidic substrate comprises a protection structure for protecting the needle, the protection structure being removably attached to the fluidic substrate.
According to embodiments of the present disclosure, the means for providing a fluid sample is an inlet. A sample drop may be inserted into the microfluidic component by means of capillary suction, or by other suitable means. The microfluidic component may comprise different fluidic compartments, for instance for multi-omic analysis. The different microfluidic compartments can have the same or different depths. The different microfluidic compartments may be separated by valves that may be actuated in any suitable way, for instance by fluidic forces or by electricity. Electrodes for actuation may be contained on the fluidic substrate or on the lid.
According to embodiments of the present disclosure, the fluidic substrate or the lid may further comprise at least one optical waveguide to allow optical excitation and sensing of the fluid sample when present in the sensing device. The fluidic substrate or the lid may also comprise filters for rejecting optical excitation from emission to measure a fluorescent signal. The fluidic substrate or the lid may comprise multispectral filters for measuring fluorescent signals with multiple colors. The fluidic substrate or the lid may comprise an optical waveguide and/or a pinhole to irradiate the sample for performing lensfree microscopy.
According to embodiments of the present disclosure, the fluidic substrate or the lid comprises at least one through-hole for application of a biochemical reagent to at least one region of the micro-fluidic component or to at least one region of the lid.
According to embodiments of the present disclosure, the lid is bonded to the fluidic substrate using a lithographically patterned polymer.
According to embodiments of the present disclosure, the sensing device may further comprise metal contacts electrically connected to the microchip for read-out of electrical signals generated by the fluid and captured by measurement systems in the lid. According to embodiments of the present disclosure, the lid of the sensing device may further comprise CMOS active pixels for readout of optical signals from the fluid.
According to embodiments of the present disclosure, at least part of the fluidic substrate and/or the lid is fabricated from a transparent material to allow optical inspection of a fluid sample in the micro-fluidic component.
According to embodiments of the present disclosure, the shape of the sensing device allows insertion into a mobile communication device.
According to an aspect, embodiments of the present disclosure relate to a method for fabricating a sensing device for analyzing a fluid sample. The method comprises: providing a fluidic substrate; providing a lid; attaching the fluidic substrate to the lid thereby at least partly close the fluidic substrate. The fluidic substrate is a semiconductor fluidic substrate and the lid is CMOS chip. The fluidic substrate is attached to the lid using a CMOS compatible bonding process.
According to embodiments of the present disclosure, providing a fluidic substrate may comprise: providing a semiconductor (e.g., silicon) substrate, providing a mask layer, for instance an oxide mask, patterning the mask layer so as to create fine structures in the oxide mask layer; providing a protection layer to protect the mask layer; patterning coarse structures; etching of the coarse structures; growing oxide for protecting the coarse structures; removing the protection layer and etch the fine structures; and removing the oxide.
Accor
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application is a divisional of U.S. application Ser. No. 15/529,441, filed on May 24, 2017, which is a 35 U.S.C. 371 National Application of PCT/EP2015/077412 filed Nov. 24, 2015, which claims priority to European Patent Application No. 14194854.7 filed on Nov. 26, 2014, the contents of each of which are hereby incorporated by reference.
TECHNICAL FIELD
The present disclosure relates to medical devices for fluid analysis. In particular, the present disclosure is related to compact devices, e.g., medical devices, for the analysis of a fluid sample. In particular, the present disclosure is related to fully integrated devices, such as lab-on-a-chip devices, for the analysis of bodily fluid samples.
BACKGROUND
A disadvantage of conventional point-of-care devices for the analysis of blood is their size which depends on the different components needed to perform analysis of blood. In these devices, external pumps are part of the point of care instrument. In some devices, miniature scale pumps are used to propagate a sample through the fluidic channels of the device. The use of pumps increases the size and cost of the device which makes them less suitable for usage as a disposable device. Current disposable devices are typically inserted in expensive read-out instruments, with many non-disposable electronic or optical components to detect the biochemical reactions taking place in the disposable device. Another disadvantage of state of the art point of care devices is their fabrication cost.
Other state of the art devices are lateral flow test strips. These test strips are usually fabricated from cellulose which does not allow precise control of the flow of a fluid sample propagating through the test strips, which can limit the applicability of these devices.
There is a need for a low-cost, easy to use, disposable, compact device for the fully integrated analysis of a fluid sample.
SUMMARY
It is an object of embodiments of the present disclosure to provide an easy to use device and method for analyzing a fluid sample.
It is an advantage of embodiments of the present disclosure that, at least for some actions, connecting the device to a separate fluid propagating element such as a pumping means can be avoided.
It is an advantage of embodiments of the present disclosure to provide compact devices for analyzing fluid samples as well as corresponding methods for analyzing fluid samples.
It is an advantage of embodiments of the present disclosure that low-cost devices for analyzing fluid samples can be provided, whereby such low-cost devices can, for example, be disposable.
This objective is accomplished by a method and device according to embodiments of the present disclosure.
According to an aspect of the disclosure, a fluid analyzing device is presented. The fluid analyzing device comprises: a sensing device for analyzing a fluid sample, the sensing device comprising: a microchip configured for sensing the fluid sample and a closed micro-fluidic component for propagating the fluid sample to the microchip. The fluid analyzing device also includes a vacuum compartment air-tight connected to the sensing device and adapted for creating a suction force in the micro-fluidic component by opening the vacuum compartment, the suction force being suitable for propagating the fluid sample through the micro-fluidic component. Further the fluid analyzing device includes an inlet for providing the fluid sample to the micro-fluidic component. Hence, the micro-fluidic component is closed off from the inlet for providing the fluid sample. The sensing device may be defined as a medical device suitable for performing an analysis of a fluid sample, e.g., bodily fluid samples.
According to an embodiment of the disclosure, the vacuum compartment encloses a volume at lower pressure than atmospheric pressure, hence creating the suction force in the micro-fluidic component by opening the vacuum compartment. Vacuum thereby means that the pressure is lower than atmospheric pressure.
According to an embodiment of the disclosure, the fluid analyzing device further comprises a package comprising: the sensing device, the vacuum compartment, and the inlet. The sensing device and the vacuum compartment are encapsulated by the package. The inlet is located in the package, e.g., in a wall of the package, and is connected to the micro-fluidic component such that a fluid sample may be provided to the micro-fluidic component.
According to an embodiment of the disclosure, the vacuum compartment comprises a sacrificial element adapted to open the vacuum compartment towards the micro-fluidic component when the element is destructed.
According to an embodiment of the disclosure, the fluid analyzing device further comprises a movable structure for destructing the sacrificial element. The movable structure may be located in the package. Alternatively, the movable structure may be part of the vacuum compartment.
According to an embodiment of the disclosure, the movable structure is a movable puncture device adapted to destruct the sacrificial element when actuated from outside the package.
According to an embodiment of the disclosure, the sacrificial element comprises a heating resistor positioned such that the sacrificial element is destructed by heating.
According to an embodiment of the disclosure, the heating resistor is positioned in or on the sacrificial element. According to an embodiment of the disclosure, the heating resistor is positioned on a substrate comprising the micro-fluidic component. The heating resistor may be in contact with the sacrificial element.
According to an embodiment of the disclosure, the sacrificial element is solvent-dissolvable. The fluid analyzing device further comprises a solvent compartment containing a solvent. The solvent compartment is configured to release the solvent to the sacrificial element when the fluid sample is provided in the micro-fluidic component. By dissolving the sacrificial element by the released solvent, the vacuum compartment is opened.
According to an embodiment of the disclosure, the fluid analyzing device further comprises a fluid detector positioned to detect the fluid sample when provided in the micro-fluidic component. When the fluid sample is detected, the vacuum compartment is configured to open.
Additionally, the fluid analyzing device also may comprise features of the sensing device described below.
According to an aspect of the disclosure, a method for sensing a fluid sample is presented, comprising: providing a fluid analyzing device; providing a fluid sample to the micro-fluidic component via the inlet for providing the fluid sample to the micro-fluidic component; thereafter propagating the fluid sample through the micro-fluidic component by opening the vacuum compartment to create a pressure difference between the vacuum compartment and the micro-fluidic component; and performing sensing on the fluid sample using the sensing device.
According to an embodiment of the disclosure, the method for sensing a fluid sample further comprises detecting a fluid sample provided to the micro-fluidic component, and wherein the vacuum compartment is opened when the fluid sample is detected.
According to an aspect of the invention, the present disclosure relates to a sensing device for analyzing a fluid sample. The sensing device comprises: a fluidic substrate comprising a micro-fluidic component embedded in the fluidic substrate, where the fluidic substrate is configured to propagate a fluid sample via capillary force through the micro-fluidic component. The sensing device also includes a means connected to the micro-fluidic component for providing a fluid sample; a lid attached to the fluidic substrate thereby at least partly covering the fluidic substrate and at least partly closing the micro-fluidic component. The fluidic substrate is a silicon fluidic substrate and the lid is a microchip (e.g., a CMOS chip).
According to embodiments of the present disclosure, at least a part of the lid is in contact with the fluid sample when the fluid sample is present in the sensing device.
According to embodiments of the present disclosure, the lid comprises a transistor layer, the transistor layer being electrically connected at least one electrical component, the electrical component being at least one of the following: biosensing circuitry, electrodes for sensing purposes, electrodes for fluid manipulation purposes, circuitry for data communication purposes, circuitry for wireless data communication purposes, temperature sensors, heater electrodes for temperature control and fluid sensors and electrodes for fluidic viscosity control, imaging components, e.g., lensfree imaging components. These electrical components may be present on the lid, hence on the microchip. In an embodiment, the transistor layer and the electrical components are integrated in a single microchip.
According to embodiments of the present disclosure, the means for providing a fluid sample is a needle fabricated from a semiconductor, e.g., silicon, and comprises an inner fluidic channel connected to the micro-fluidic component. The needle is a protruding portion of the fluidic substrate and positioned to penetrate skin tissue when pressed against the skin tissue.
According to embodiments of the present disclosure, the fluidic substrate comprises a cut-out and the needle is positioned in the cut-out.
According to embodiments of the present disclosure, the fluidic substrate comprises a protection structure for protecting the needle, the protection structure being removably attached to the fluidic substrate.
According to embodiments of the present disclosure, the means for providing a fluid sample is an inlet. A sample drop may be inserted into the microfluidic component by means of capillary suction, or by other suitable means. The microfluidic component may comprise different fluidic compartments, for instance for multi-omic analysis. The different microfluidic compartments can have the same or different depths. The different microfluidic compartments may be separated by valves that may be actuated in any suitable way, for instance by fluidic forces or by electricity. Electrodes for actuation may be contained on the fluidic substrate or on the lid.
According to embodiments of the present disclosure, the fluidic substrate or the lid may further comprise at least one optical waveguide to allow optical excitation and sensing of the fluid sample when present in the sensing device. The fluidic substrate or the lid may also comprise filters for rejecting optical excitation from emission to measure a fluorescent signal. The fluidic substrate or the lid may comprise multispectral filters for measuring fluorescent signals with multiple colors. The fluidic substrate or the lid may comprise an optical waveguide and/or a pinhole to irradiate the sample for performing lensfree microscopy.
According to embodiments of the present disclosure, the fluidic substrate or the lid comprises at least one through-hole for application of a biochemical reagent to at least one region of the micro-fluidic component or to at least one region of the lid.
According to embodiments of the present disclosure, the lid is bonded to the fluidic substrate using a lithographically patterned polymer.
According to embodiments of the present disclosure, the sensing device may further comprise metal contacts electrically connected to the microchip for detecting electrical signals generated by the fluid and captured by measurement systems in the lid. According to embodiments of the present disclosure, the lid of the sensing device may further comprise CMOS active pixels for detecting optical signals from the fluid.
According to embodiments of the present disclosure, the fluidic substrate comprises a cut-out and the needle is positioned in the cut-out.
According to embodiments of the present disclosure, the fluidic substrate comprises a protection structure for protecting the needle, the protection structure being removably attached to the fluidic substrate.
According to embodiments of the present disclosure, the means for providing a fluid sample is an inlet. A sample drop may be inserted into the microfluidic component by means of capillary suction, or by other suitable means. The microfluidic component may comprise different fluidic compartments, for instance for multi-omic analysis. The different microfluidic compartments can have the same or different depths. The different microfluidic compartments may be separated by valves that may be actuated in any suitable way, for instance by fluidic forces or by electricity. Electrodes for actuation may be contained on the fluidic substrate or on the lid.
According to embodiments of the present disclosure, the fluidic substrate or the lid may further comprise at least one optical waveguide to allow optical excitation and sensing of the fluid sample when present in the sensing device. The fluidic substrate or the lid may also comprise filters for rejecting optical excitation from emission to measure a fluorescent signal. The fluidic substrate or the lid may comprise multispectral filters for measuring fluorescent signals with multiple colors. The fluidic substrate or the lid may comprise an optical waveguide and/or a pinhole to irradiate the sample for performing lensfree microscopy.
According to embodiments of the present disclosure, the fluidic substrate or the lid comprises at least one through-hole for application of a biochemical reagent to at least one region of the micro-fluidic component or to at least one region of the lid.
According to embodiments of the present disclosure, the lid is bonded to the fluidic substrate using a lithographically patterned polymer.
According to embodiments of the present disclosure, the sensing device may further comprise metal contacts electrically connected to the microchip for read-out of electrical signals generated by the fluid and captured by measurement systems in the lid. According to embodiments of the present disclosure, the lid of the sensing device may further comprise CMOS active pixels for readout of optical signals from the fluid.
According to embodiments of the present disclosure, at least part of the fluidic substrate and/or the lid is fabricated from a transparent material to allow optical inspection of a fluid sample in the micro-fluidic component.
According to embodiments of the present disclosure, the shape of the sensing device allows insertion into a mobile communication device.
According to an aspect, embodiments of the present disclosure relate to a method for fabricating a sensing device for analyzing a fluid sample. The method comprises: providing a fluidic substrate; providing a lid; attaching the fluidic substrate to the lid thereby at least partly close the fluidic substrate. The fluidic substrate is a semiconductor fluidic substrate and the lid is CMOS chip. The fluidic substrate is attached to the lid using a CMOS compatible bonding process.
According to embodiments of the present disclosure, providing a fluidic substrate may comprise: providing a semiconductor (e.g., silicon) substrate, providing a mask layer, for instance an oxide mask, patterning the mask layer so as to create fine structures in the oxide mask layer; providing a protection layer to protect the mask layer; patterning coarse structures; etching of the coarse structures; growing oxide for protecting the coarse structures; removing the protection layer and etch the fine structures; and removing the oxide.
According to embodiments of the present disclosure, providing a fluidic substrate may comprise providing a semiconductor substrate, providing a plurality of masks on top of one another, and using each mask for creating microfluidic structures of different depths.
In accordance with particular embodiments of the present disclosure, providing a fluidic substrate may comprise providing a semiconductor (e.g., silicon) substrate, providing a first oxide mask, patterning microfluidic structures, etching the substrate to single depth, providing a second oxide mask, patterning microfluidic structures, etching the substrate to a second depth, and, if required, repeating these steps for creating multiple depths of microfluidic structures.
According to particular embodiments, the fluidic substrate and the lid of a sensing device according to embodiments of the present disclosure may be integrated in a larger fluidic package, which may be made from different materials such as polymers, and which may contain larger fluidic structures, reagents, fluidic and electrical interfaces. The advantage thereof is that such system becomes more cost efficient.
According to embodiments of the present disclosure, surfaces of the fluidic substrate and the lid may be partially or fully coated to modify surface interactions of the substrate with the fluid sample.
According to an aspect of the disclosure, the present invention provides the use of the sensing device as described in the foregoing aspects to perform microscopy. Microscopy may be implemented by using the lid for detecting lensfree images according to the principles of digital holography.
The use of the sensing device as described may perform multi-omic analysis in which the fluidic substrate is used for performing multiple assays in multiple channels and chambers, and the CMOS lid is used to detect multiple signals from all assays. Those signals can combine multiple DNA, RNA, small molecule, cell signals from a same analyte.
In particular embodiments, the sensing device is used as a single use disposable device for analysis of a small amount of fluid.
According to an aspect of the disclosure, the data from the microchip may be sent to a smart handheld device, for instance using a wireless connection. The smart device can be used for processing, visualizing and/or transferring the data.
In embodiments of the present disclosure, the combined data gathered from a single same sample may be used in a software algorithm for calculating a parameter indicative of disease or of the wellbeing of an individual.
Example aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims.
These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 illustrates a 3D view of an embodiment of a fluidic substrate, according to an example embodiment.
FIG. 2 illustrates a top view of a first embodiment of a sensing device for analyzing a fluid sample, according to an example embodiment.
FIG. 3 illustrates a top view of a fluidic substrate used in the sensing device of FIG. 2 , according to an example embodiment.
FIG. 4 illustrates a side view of the sensing device of FIG. 2 , according to an example embodiment.
FIG. 5 illustrates a top view of a sensing device, for analyzing a fluid, featuring a cut-out for a needle, according to an example embodiment.
FIG. 6 illustrates a top view of an embodiment of a fluidic substrate featuring a cut-out for a needle, for use in the sensing device of FIG. 5 , according to an example embodiment.
FIG. 7 illustrates a side view of the sensing device of FIG. 5 , according to an example embodiment.
FIG. 8 illustrates a top view of a sensing device, for analyzing a fluid sample, featuring a protection structure for a needle, according to an example embodiment.
FIG. 9 illustrates a top view of an embodiment of a fluidic substrate featuring a protection structure for a needle, for use in the sensing device of FIG. 8 , according to an example embodiment.
FIG. 10 illustrates a side view of the sensing device of FIG. 8 , according to an example embodiment.
FIG. 11 , FIG. 12 , FIG. 13 , FIG. 14 , FIG. 15 , FIG. 16 , and FIG. 17 illustrate a method to fabricate a fluidic substrate for use in a sensing device, according to example embodiments.
FIG. 18 illustrates an embodiment of a CMOS chip for use in a sensing device, according to an example embodiment.
FIG. 19 illustrates the bonding of a CMOS chip with a fluidic substrate, according to an example embodiment.
FIG. 20 illustrates the bonding of a CMOS chip with a fluidic substrate, where the CMOS chip comprises a silicon I/O interconnect, according to an example embodiment.
FIG. 21 illustrates an embodiment of a CMOS chip for use in a sensing device, the CMOS chip comprising an I/O pad, according to an example embodiment.
FIG. 22 illustrates an embodiment of a CMOS chip for use in a sensing device, the CMOS chip comprising an I/O pad bonded to a fluidic substrate, according to an example embodiment.
FIG. 23 illustrates the bonding of a CMOS chip with a fluidic substrate, according to an example embodiment.
FIG. 24 illustrates the bonding of a CMOS chip with a fluidic substrate, according to an example embodiment.
FIG. 25 illustrates a 3D view of a sensing device, according to an example embodiment.
FIG. 26 illustrates a 3D view of a wireless stand-alone sensing device, according to an example embodiment.
FIG. 27 illustrates a top view of a part of a micro-fluidic component for use in a sensing device, the micro-fluidic component comprising micro-pillars, according to an example embodiment.
FIG. 28 illustrates a 3D view of a part of the micro-fluidic component of FIG. 27 , according to an example embodiment.
FIG. 29 illustrates a top view of a part of a second embodiment of a micro-fluidic component for use in a sensing device, the micro-fluidic component comprising micro-pillars, according to an example embodiment.
FIG. 30 illustrates a 3D view of a part of the micro-fluidic component of FIG. 29 , according to an example embodiment.
FIG. 31 illustrates a sensing device in the shape of an SD card, according to an example embodiment.
FIG. 32 illustrates another sensing device in the shape of an SD card, according to an example embodiment.
FIG. 33 is a cross-sectional view of a sensing device, according to an example embodiment.
FIG. 34 illustrates a fluid analyzing device, according to an example embodiment.
FIG. 35 illustrates another fluid analyzing device, according to an example embodiment.
The drawings are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes.
Any reference signs in the claims shall not be construed as limiting the scope.
In the different drawings, the same reference signs refer to the same or analogous elements.
DETAILED DESCRIPTION
The present disclosure will be described with respect to particular embodiments and with reference to certain drawings but the invention is not limited thereto. The drawings described are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes. The dimensions and the relative dimensions do not correspond to actual reductions to practice of the disclosure.
Furthermore, the terms first, second and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequence, either temporally, spatially, in ranking or in any other manner. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.
Moreover, the terms top, under and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the disclosure described herein are capable of operation in other orientations than described or illustrated herein.
It is to be noticed that the term âcomprisingâ, used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. It is thus to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. Thus, the scope of the expression âa device comprising means A and Bâ should not be limited to devices consisting only of components A and B. It means that with respect to the present disclosure, the only relevant components of the device are A and B.
Reference throughout this specification to âone embodimentâ or âan embodimentâ means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, appearances of the phrases âin one embodimentâ or âin an embodimentâ in various places throughout this specification are not necessarily all referring to the same embodiment, but may be doing so. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments.
Similarly it should be appreciated that in the description of exemplary embodiments of the disclosure, various features of the disclosure are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the disclosure requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this disclosure.
Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the disclosure, and form different embodiments, as would be understood by those in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.
In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the disclosure may be practiced without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.
Where in embodiments of the present disclosure reference is made to an âI/O padâ or an âI/O contactâ, reference is made to a contact such as a metal contact allowing input and output of electrical signals of a micro-chip.
Where in embodiments of the present disclosure reference is made to âCMOSâ, reference is made to a Complementary Metal-Oxide Semiconductor.
Throughout the description reference is made to âfluid sampleâ. This may refer to biological fluids including but not limited to blood, serum, urine, gastric and digestive juices, tears, saliva, stool, semen, and interstitial fluids derived from tumorous tissues.
According to an aspect of the disclosure, a fluid analyzing device 1 is presented (shown in FIG. 34 ). The fluid analyzing device 1 comprises a sensing device 100 which is adapted for analyzing a fluid sample. The sensing device 100 comprises a closed micro-fluidic component 4 for propagating the fluid sample to a microchip 103 which is disposed in the sensing device 100 . The fluid analyzing device 1 further comprises an inlet for providing the fluid sample to the micro-fluidic component 4 . Further, the fluid analyzing device 1 comprises a vacuum compartment 6 which is air-tight connected or attached to the micro-fluidic device 4 . The micro-fluidic component 4 is embedded in a substrate (e.g., glass or silicon substrate) and thus is closed off from the inlet, and apart from the location where the vacuum compartment 6 is air tight connected to the sensing device 100 . By opening the vacuum compartment 6 at the side attached to the sensing device 100 , a suction force is created in the micro-fluidic component 4 which allows a fluid sample present in part of the micro-fluidic component 4 to propagate through the micro-fluidic component 4 . By using a vacuum compartment to create the suction force, a cheap, power-free and reliable way of propagating the fluid sample is devised which makes it extremely suitable for use in single usage, disposable medical devices. (In this text and accompanying figures, the micro-fluidic component may be referred to with reference number â4â or with reference number â102â).
According to an embodiment of the disclosure, the fluid analyzing device 1 further comprises a package 2 comprising the sensing device 100 , the vacuum compartment 6 and the inlet 7 . The package 2 encapsulates the sensing device 100 , the vacuum compartment 6 and protects the fluid analyzing device 1 from the environment. For example, the package may be dust, water or shock proof. The package may be fabricated from a resilient material, e.g., a plastic. The inlet 7 in the package 2 is fluidically connected to the inlet of the micro-fluidic component 4 . A fluid sample can be provided to the micro-fluidic component 4 via the inlet 7 of the package 2 . If the micro-fluidic component 4 comprises multiple inlets, the package 2 may also comprise multiple corresponding inlets.
According to an embodiment of the disclosure, the micro-fluidic component 4 is fluidically connected on one end with the inlet 7 and fluidically connectable on the other end with the vacuum compartment 6 , by opening the vacuum compartment 6 . In some embodiments of the present invention, the vacuum compartment pressure is lower than atmospheric pressure. When the vacuum compartment 6 is opened, the pressure difference between the micro-fluidic component 4 and the vacuum compartment 6 forces a fluid sample which is provided at the inlet for the micro-fluidic component 4 to propagate through the micro-fluidic component 4 , at least until the fluid sample reaches the microchip 103 .
According to an embodiment of the disclosure, the vacuum compartment 6 is part of the sensing device. For example, the vacuum compartment may be a compartment located in the substrate that also comprises the micro-fluidic component 4 . In such an embodiment, the compartment 6 may be a sealed cavity in the substrate which can be connected to the micro-fluidic component 4 by breaking the seal which seals the cavity. The seal may be a sacrificial element 8 , such as a membrane, which can be destructed by suitable means, such as dissolution, by heating or by applying a force, for example an external pushing pressure.
According to an embodiment of the disclosure, to reduce cost and to minimize the usage of substrate material, the vacuum compartment 6 may be a separate component which is attached to the sensing device 100 .
According to an embodiment of the disclosure, the vacuum compartment 6 may also be a part of the package 2 , e.g., attached to the inside the package. For example, the vacuum compartment is attached to or is part of an inner wall of the package.
Different embodiments for the sacrificial element 8 may be provided. According to embodiments of the disclosure, the vacuum compartment 6 comprises a sacrificial element 8 which is adapted to open the vacuum compartment 6 towards the micro-fluidic component 102 when the element 8 is broken. The sacrificial element 8 is located such that when the element is broken, a suction force in the micro-fluidic component 102 can be created while maintaining the air-tight connection between the vacuum compartment 6 and the sensing device 100 . The sacrificial element 8 may be a membrane, e.g., a sealing foil. The material and thickness of the sacrificial element is selected such that its resistance is sufficiently high thereby making it suitable for sealing the vacuum compartment 6 .
According to an embodiment of the disclosure, the sacrificial element 8 comprises a heating element, such as for example a heating resistor, positioned such that the sacrificial element 8 is broken by heating when the heating element is electrically driven, thereby opening the vacuum compartment 6 . Other variations of this method describing different method steps for breaking the sacrificial element 8 also correspond with embodiments of the present invention.
According to an embodiment of the disclosure, the heating element is positioned in or on the sacrificial element 8 . According to an embodiment of the disclosure, the heating resistor is positioned on the sensing device 100 , for example on the substrate which comprises the micro-fluidic component 4 . The heating element may be in direct contact with the sacrificial element 8 . In such an embodiment, the heating element is isolated from other parts of the substrate to minimize heat transfer to other components on the substrate. For example, the sensing device 100 , e.g., the substrate comprising the micro-fluidic component 102 , may comprise trenches located around the heating element to isolate the element from the rest of the sensing device 100 .
The cross-section of a device according to an embodiment of the disclosure is illustrated in FIG. 34 . A package 2 encapsulates a sensing device 100 . This package is not essential. The sensing device 100 is fixed inside the package 2 , e.g., via clamps. The sensing device 100 is positioned inside the package 2 such that a fluid sample introduced in the inlet 7 can enter the micro-fluidic component 4 , e.g., via an inlet of the micro-fluidic component 4 . A vacuum compartment 6 is attached to the sensing device 100 . A microchip 103 is part of the sensing device 100 and is positioned such that it may perform direct sensing on a fluid sample inside the micro-fluidic component 4 . The inlet 7 is connected to one end of the <figure-callout id="4" label="micro-fluidic component" filenames="US11684915-20230627-D00016.png,US11684
CLAIMS
Claims ( 12 )
What is claimed is:
1. A fluid analyzing device comprising:
a sensing device for analyzing a fluid sample, the sensing device comprising:
a microchip configured for sensing the fluid sample; and
a micro-fluidic component for propagating the fluid sample to the microchip;
an inlet coupled to the micro-fluidic component, wherein the inlet is configured for providing the fluid sample to the micro-fluidic component;
a switch electrically coupled to an on-board energy source; and
a vacuum compartment air-tight connected to the sensing device, wherein the vacuum compartment comprises a sacrificial element separating the vacuum compartment from the sensing device, wherein the on-board energy source electrically drives the sacrificial element to cause the vacuum compartment to open when the switch is actuated, and wherein opening the vacuum compartment creates a suction force in the micro-fluidic component suitable for propagating the fluid sample through the micro-fluidic component when the sacrificial element is broken.
2. The fluid analyzing device of claim 1 , further comprising:
a package comprising the sensing device, the inlet, and the vacuum compartment.
3. The fluid analyzing device of claim 1 , further comprising a movable structure for breaking the sacrificial element.
4. The fluid analyzing device of claim 3 , wherein the movable structure comprises a mechanical structure coupled to a needle inside the vacuum compartment, wherein the mechanical structure comprises a spring configured to actuate the needle, and wherein the needle is configured to break the sacrificial element when actuated.
5. The fluid analyzing device of claim 1 , further comprising a heating element positioned such that the sacrificial element is broken by way of heat from the heating element.
6. The fluid analyzing device of claim 5 , wherein the heating element is positioned in or on the sacrificial element.
7. The fluid analyzing device of claim 5 , wherein the heating element is positioned on a substrate comprising the micro-fluidic component.
8. The fluid analyzing device of claim 1 , wherein the microchip is a CMOS chip, and wherein the sensing device further comprises:
a silicon fluidic substrate comprising the micro-fluidic component embedded in the silicon fluidic substrate, wherein the silicon fluidic substrate is fluidically connected to the inlet.
9. The fluid analyzing device of claim 8 , wherein the CMOS chip comprises a transistor layer, the transistor layer being electrically connected to at least one electrical component, the electrical component being at least one of: biosensing circuitry, electrodes for sensing purposes, electrodes for fluid manipulation purposes, circuitry for data communication purposes, circuitry for wireless data communication purposes, temperature sensors, heater electrodes for temperature control, and fluid sensors and electrodes for fluidic viscosity control.
10. The fluid analyzing device of claim 8 , wherein the CMOS chip is a lid attached to the silicon fluidic substrate, and wherein the CMOS chip at least partly covers the silicon fluidic substrate and at least partly closes the micro-fluidic component.
11. The fluid analyzing device of claim 1 , further comprising:
a sealing layer disposed between the sensing device and the vacuum compartment, wherein the sealing layer bonds the vacuum compartment to the sensing device.
12. A method for sensing a fluid sample, comprising:
providing a fluid analyzing device comprising:
a sensing device comprising:
a microchip configured for sensing the fluid sample; and
a micro-fluidic component for propagating the fluid sample to the microchip;
an inlet coupled to the micro-fluidic component, wherein the inlet is configured for providing the fluid sample to the micro-fluidic component;
a switch electrically coupled to an on-board energy source; and
a vacuum compartment air-tight connected to the sensing device, wherein the vacuum compartment comprises a sacrificial element, separating the vacuum compartment from the sensing device, wherein the on-board energy source electrically drives the sacrificial element to cause the vacuum compartment to open when the switch is activated, and wherein opening the vacuum compartment creates a suction force in the micro-fluidic component suitable for propagating a fluid sample through the micro-fluidic component when the sacrificial element is broken; and
providing a fluid sample to the micro-fluidic component;
detecting the fluid sample being provided to the micro-fluidic component;
opening the vacuum compartment when the fluid sample is detected;
propagating the fluid sample through the micro-fluidic component by opening the vacuum compartment thereby creating a pressure difference between the vacuum compartment and the micro-fluidic component; and
sensing the fluid sample using the sensing device.
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ì ëë²ìí° ì¤ë¸ ì í 리ì¨ì¹ íì´ë°ì´ì
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Citations (23)
* Cited by examiner, â Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
US5006202A
( en )
1990-06-04
1991-04-09
Xerox Corporation
Fabricating method for silicon devices using a two step silicon etching process
US5055203A
( en )
*
1990-05-22
1991-10-08
Eastman Kodak Company
Blood collection device with reduced serum dispensing volume and integral needle
US5385635A
( en )
1993-11-01
1995-01-31
Xerox Corporation
Process for fabricating silicon channel structures with variable cross-sectional areas
WO1998050154A1
( en )
1997-05-08
1998-11-12
University Of Minnesota
Integrated microchip genetic testing system
US5919712A
( en )
1993-05-18
1999-07-06
University Of Utah Research Foundation
Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays
US6123820A
( en )
1998-06-05
2000-09-26
Grupo Ch-Werfen, S.A.
Sensor cartridges
US20020022261A1
( en )
1995-06-29
2002-02-21
Anderson Rolfe C.
Miniaturized genetic analysis systems and methods
US20020142471A1
( en )
*
2001-03-28
2002-10-03
Kalyan Handique
Methods and systems for moving fluid in a microfluidic device
US20030019522A1
( en )
*
2001-07-26
2003-01-30
Gene Parunak
Methods and systems for fluid control in microfluidic devices
US20060078475A1
( en )
2004-07-29
2006-04-13
Yu-Chong Tai
Modular microfluidic packaging system
US20060153736A1
( en )
*
2003-09-09
2006-07-13
Kalra Krishan L
Sample processing system
US20070172388A1
( en )
2004-05-14
2007-07-26
Honeywell International Inc.
Portable sample analyzer system
US20070281288A1
( en )
*
2004-01-27
2007-12-06
Shimshon Belkin
Method and System for Detecting Analytes
EP2011574A1
( en )
2007-07-02
2009-01-07
STMicroelectronics (Research & Development) Limited
Assaying device and method of transporting a fluid in an assaying device
US20090169427A1
( en )
2007-12-28
2009-07-02
Lakshmi Supriya
Controlled fluid delivery in a microelectronic package
US20090317302A1
( en )
2008-06-20
2009-12-24
Silverbrook Research Pty Ltd
Microfluidic System Comprising MEMS Integrated Circuit
US20110201099A1
( en )
2009-12-07
2011-08-18
Meso Scale Technologies, Llc.
Assay Cartridges and Methods of Using the Same
WO2012054904A2
( en )
2010-10-21
2012-04-26
The Regents Of The University Of California
Microfluidics with wirelessly powered electronic circuits
US20130189796A1
( en )
2012-01-20
2013-07-25
Ortho-Clinical Diagnostics, Inc.
Assay Device Having Uniform Flow Around Corners
US20140322706A1
( en )
*
2012-10-24
2014-10-30
Jon Faiz Kayyem
Integrated multipelx target analysis
WO2014187926A1
( en )
2013-05-22
2014-11-27
Imec Vzw
Compact fluid analysis device and method to fabricate
US20150320349A1
( en )
*
2011-04-29
2015-11-12
Seventh Sense Biosystems, Inc.
Plasma or serum production and removal of fluids under reduced pressure
US20160199834A1
( en )
*
2015-01-14
2016-07-14
Pixcell Medical Technologies Ltd
Disposable cartridge for sample fluid analysis
2015
2015-11-24
US
US15/529,441
patent/US20170326552A1/en
not_active
Abandoned
2015-11-24
EP
EP15801735.0A
patent/EP3223946B1/en
active
Active
2015-11-24
WO
PCT/EP2015/077412
patent/WO2016083329A1/en
not_active
Ceased
2018
2018-08-08
US
US16/058,828
patent/US11684915B2/en
active
Active
Patent Citations (24)
* Cited by examiner, â Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
US5055203A
( en )
*
1990-05-22
1991-10-08
Eastman Kodak Company
Blood collection device with reduced serum dispensing volume and integral needle
US5006202A
( en )
1990-06-04
1991-04-09
Xerox Corporation
Fabricating method for silicon devices using a two step silicon etching process
US5919712A
( en )
1993-05-18
1999-07-06
University Of Utah Research Foundation
Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays
US5385635A
( en )
1993-11-01
1995-01-31
Xerox Corporation
Process for fabricating silicon channel structures with variable cross-sectional areas
US20020022261A1
( en )
1995-06-29
2002-02-21
Anderson Rolfe C.
Miniaturized genetic analysis systems and methods
WO1998050154A1
( en )
1997-05-08
1998-11-12
University Of Minnesota
Integrated microchip genetic testing system
US6123820A
( en )
1998-06-05
2000-09-26
Grupo Ch-Werfen, S.A.
Sensor cartridges
US20020142471A1
( en )
*
2001-03-28
2002-10-03
Kalyan Handique
Methods and systems for moving fluid in a microfluidic device
US20030019522A1
( en )
*
2001-07-26
2003-01-30
Gene Parunak
Methods and systems for fluid control in microfluidic devices
US20060153736A1
( en )
*
2003-09-09
2006-07-13
Kalra Krishan L
Sample processing system
US20070281288A1
( en )
*
2004-01-27
2007-12-06
Shimshon Belkin
Method and System for Detecting Analytes
US20070172388A1
( en )
2004-05-14
2007-07-26
Honeywell International Inc.
Portable sample analyzer system
US20060078475A1
( en )
2004-07-29
2006-04-13
Yu-Chong Tai
Modular microfluidic packaging system
EP2011574A1
( en )
2007-07-02
2009-01-07
STMicroelectronics (Research & Development) Limited
Assaying device and method of transporting a fluid in an assaying device
US20090169427A1
( en )
2007-12-28
2009-07-02
Lakshmi Supriya
Controlled fluid delivery in a microelectronic package
US20090317302A1
( en )
2008-06-20
2009-12-24
Silverbrook Research Pty Ltd
Microfluidic System Comprising MEMS Integrated Circuit
US20110201099A1
( en )
2009-12-07
2011-08-18
Meso Scale Technologies, Llc.
Assay Cartridges and Methods of Using the Same
WO2012054904A2
( en )
2010-10-21
2012-04-26
The Regents Of The University Of California
Microfluidics with wirelessly powered electronic circuits
US20150320349A1
( en )
*
2011-04-29
2015-11-12
Seventh Sense Biosystems, Inc.
Plasma or serum production and removal of fluids under reduced pressure
US20130189796A1
( en )
2012-01-20
2013-07-25
Ortho-Clinical Diagnostics, Inc.
Assay Device Having Uniform Flow Around Corners
US20140322706A1
( en )
*
2012-10-24
2014-10-30
Jon Faiz Kayyem
Integrated multipelx target analysis
WO2014187926A1
( en )
2013-05-22
2014-11-27
Imec Vzw
Compact fluid analysis device and method to fabricate
US20150093816A1
( en )
2013-05-22
2015-04-02
Imec Vzw
Compact Fluid Analysis Device and Method to Fabricate
US20160199834A1
( en )
*
2015-01-14
2016-07-14
Pixcell Medical Technologies Ltd
Disposable cartridge for sample fluid analysis
Non-Patent Citations (4)
* Cited by examiner, â Cited by third party
Title
Lee, Hakho et al., " IC/Microfuidic Hybrid System for Magnetic Manipulation of Biological Cells ", IEEE Journal of Solid-State Circuits, vol. 41, No. 6, Jun. 6, 2006, pp. 1471-1480.
PCT International Search Report and Written Opinion, PCT International Application No. PCT/EP2015/077412, dated Mar. 1, 2016, 8 pages.
PCT International Search Report and Written Opinion, PCT International Application No. PCT/EP2015/077439, dated Feb. 15, 2016, 8 pages.
Tanaka, Hiroyuki et al., " Electrochemical Sensor with Dry Reagents Implemented in Lab-on-Chip for Single Nucleotide Polymorphism Detection, " Japanese Journal of Applied Physics, vol. 53, Apr. 17, 2014, pp. 1-5.
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