The application claims priority to Chinese patent application No. 201710797437.6 filed on Sep. 6, 2017, the entire disclosure of which is incorporated herein by reference as part of the present application.
At least one embodiment of the present disclosure relates to a micro-total analysis system and a method thereof.
A micro-total analysis system (μTAS) aims to maximize the transfer of functions of an analytical laboratory to a portable analytical apparatus and even into a square-inch-sized chip through miniaturization and integration of a chemical analysis apparatus. An ultimate goal of the micro-total analysis system is to realize the “personalization” and “home-use” of the analytical laboratory, which frees analytical science and analytical instruments from the chemical laboratory and enters thousands of households.
At least an example of the present disclosure relates a micro-total analysis system (μTAS) and a method thereof. The micro-total analysis system has a high degree of integration and can realize operation and detection of the liquid to be detected and/or components of the liquid.
At least an example of the present disclosure provides a micro-total analysis system, comprising: a microfluidic device, configured to accommodate a liquid to be detected; an optical unit, configured to form a first light irradiated to the microfluidic device; and a detection unit, configured to detect the liquid to be detected and output a detection signal to obtain detection information.
According to a micro-total analysis system provided by some examples of the present disclosure, the microfluidic device comprises a first base substrate and a second base substrate opposite to each other, the detection unit is located on a side of the first base substrate close to the second base substrate or on a side of the first base substrate away from the second base substrate, and the optical unit is located on a side of the second base substrate away from the first base substrate.
According to a micro-total analysis system provided by some examples of the present disclosure, the microfluidic device comprises a first electrode located on the side of the first base substrate close to the second base substrate, and a second electrode located on a side of the second base substrate close to the first base substrate, the first electrode comprises a plurality of first sub-electrodes insulated from each other, each of the plurality of first sub-electrodes is connected with a first thin film transistor, and a space between the first base substrate and second base substrate is configured to accommodate the liquid to be detected.
According to a micro-total analysis system provided by some examples of the present disclosure, the optical unit comprises a light source, a light guide plate, and a grating, the light guide plate is disposed opposite to the second base substrate, the light source is located on a side surface of the light guide plate, the grating is located on a side of the light guide plate close to the first base substrate, the light source is configured to emit a second light, the light guide plate is configured to transmit the second light, and the grating is configured to adjust the second light transmitted from the light guide plate to the first light, and emit the first light toward the microfluidic device.
According to a micro-total analysis system provided by some examples of the present disclosure, the light source comprises a laser light source.
According to a micro-total analysis system provided by some examples of the present disclosure, the grating comprises a first grating portion and a second grating portion, the first grating portion and the second grating portion are configured to form the first light being different in feature, and the feature comprises at least one of wavelength and intensity.
According to a micro-total analysis system provided by some examples of the present disclosure, the second base substrate is also taken as the light guide plate.
According to a micro-total analysis system provided by some examples of the present disclosure, the detection unit is located on a side of the first base substrate close to the second base substrate.
According to a micro-total analysis system provided by some examples of the present disclosure, the detection unit comprises a sensor group.
According to a micro-total analysis system provided by some examples of the present disclosure, the sensor group comprises an optical sensor, the optical sensor is configured to detect a third light, and the third light is a light transmitted to the optical sensor after the first light passing through the liquid to be detected.
According to a micro-total analysis system provided by some examples of the present disclosure, the third light is a fluorescence emitted by the liquid to be detected under the excitation of the first light.
According to a micro-total analysis system provided by some examples of the present disclosure, the sensor group comprises a plurality of second thin film transistors and a plurality of photosensitive diodes, each of the plurality of photosensitive diodes is respectively connected with one of the plurality of second thin film transistors, the plurality of second thin film transistors are arranged in an array, second thin film transistors in a same row are connected to a same gate line, and second thin film transistors in a same column are connected to a same data line.
According to a micro-total analysis system provided by some examples of the present disclosure, the sensor group comprises a capacitive sensor; the microfluidic device comprises a first electrode disposed on the first base substrate, and a second electrode disposed on the second base substrate, the second electrode is insulated from the first electrode, the first electrode and the second electrode are configured to drive the liquid to be detected in a first period, and configured to output a capacitance signal between the first electrode and the second electrode in a second period, and the first electrode and the second electrode constitute the capacitive sensor.
According to a micro-total analysis system provided by some examples of the present disclosure, the first electrode comprises a plurality of sub-potions insulated from each other, each of the plurality of sub-portions comprises a plurality of first sub-electrodes insulated from each other, each of the plurality of first sub-electrodes is connected with a first thin film transistor, the second electrode comprises a plurality of second sub-electrodes insulated from each other, and each of the second sub-electrodes and a corresponding one of the sub-portions have an overlapping portion in a direction perpendicular to the first base substrate.
According to a micro-total analysis system provided by some examples of the present disclosure, the sensor group comprises at least two different types of sensors, a same type of sensors comprises a plurality of sensors, and the plurality of sensors of the same type are arranged uniformly.
At least an example of the present disclosure provides a micro-total analysis method, comprising: accommodating a liquid to be detected in a microfluidic device; forming a first light irradiated to the microfluidic device; and detecting the liquid to be detected and outputting a detection signal to obtain detection information.
According to a micro-total analysis method provided by some examples of the present disclosure, the liquid to be detected generates fluorescence under excitation of the first light, and the detection unit is irradiated with the fluorescence and outputs the detection signal according to the fluorescence.
According to a micro-total analysis method provided by some examples of the present disclosure, the microfluidic device comprises a first electrode on a side of a first base substrate close to a second base substrate and a second electrode disposed on a side of the second base substrate close to the first base substrate, the second electrode is insulated from the first electrode, the first base substrate and the second base substrate are opposite to each other, driving and capacitance detection are performed in a time-division mode, and the micro-total analysis method comprises: driving the liquid to move by using the first electrode and the second electrode in a first period; and outputting a capacitance signal between the first electrode and the second electrode in a second period.
According to a micro-total analysis method provided by some examples of the present disclosure, in the first period, a common signal is input to the second electrode and a first driving signal is input to the first electrode, and the micro-total analysis method further comprises adjusting the first driving signal in real time based on a result of the capacitance detection.
A micro-total analysis method provided by some examples of the present disclosure comprises a plurality of time spans, each of the plurality of time spans comprises the first period and the second period, and the first driving signal input to the first electrode in a subsequent time span is adjusted in real time according to the result of the capacitance detection in a previous time span that before the subsequent time span.
In order to clearly illustrate the technical solution of the embodiments of the present disclosure, the drawings of the embodiments will be briefly described in the following. It is obvious that the described drawings in the following are only related to some embodiments of the present disclosure and thus are not limitative of the present disclosure.
In order to make objects, technical details and advantages of the embodiments of the disclosure apparent, the technical solutions of the embodiments will be described in a clearly and fully understandable way in connection with the drawings related to the embodiments of the disclosure. Apparently, the described embodiments are just a part but not all of the embodiments of the disclosure. Based on the described embodiments herein, those skilled in the art can obtain other embodiment(s), without any inventive work, which should be within the scope of the disclosure.
Unless otherwise defined, all the technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. The terms “first,” “second,” etc., which are used in the description and the claims of the present application for disclosure, are not intended to indicate any sequence, amount or importance, but distinguish various components. Also, the terms such as “a,” “an,” etc., are not intended to limit the amount, but indicate the existence of at least one. The terms “comprise,” “comprising,” “include,” “including,” etc., are intended to specify that the elements or the objects stated before these terms encompass the elements or the objects and equivalents thereof listed after these terms, but do not preclude the other elements or objects. The phrases “connect”, “connected”, “coupled”, etc., are not intended to define a physical connection or mechanical connection, but may include an electrical connection, directly or indirectly. “On,” “under,” “right,” “left” and the like are only used to indicate relative position relationship, and when the position of the object which is described is changed, the relative position relationship may be changed accordingly.
A microfluidic device or a microfluidic chip is the current hotspot in a micro-total analysis system (μTAS), and the microfluidic device or the microfluidic chip best embodies the idea of transferring functions of an analytical laboratory to a chip.
The conventional microfluidic chip is designed for a specific application, with a single function, thus only used for transporting, separating and combining droplets or other operations. A complete test system may be constituted together with a microscope system, a light source system, an operating environment detection system, or the like.
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The micro-total analysis system/detection platform provided by at least an example of the present disclosure has a high degree of integration and intelligence, can not only perform operations such as movement (transportation), separation and combination, and reaction of liquid/liquid 131 to be detected, but also to implement the detection of the liquid 131 to be detected, and has a small size and is operated flexibly and conveniently. For example, the liquid can be passed into the microfluidic device, and the liquid 131 to be detected may be a liquid obtained after the liquid passed into the microfluidic device and reacted therein, and the examples of the present disclosure are not limited thereto.
For example, the first light L1 is irradiated to the liquid 131 to be detected in the microfluidic device 10, a third light L3 is obtained after the first light L1 transmits through the liquid 131 to be detected, and the third light L3 is irradiated to the detection unit 30. For example, the detection information of the liquid to be detected can be obtained by the information of the third light L3 detected by the detection unit 30, such as a light intensity, brightness, or the like. For example, the detection information includes at least one of whether the liquid 131 to be detected reacts, a degree of reaction, a substance to be detected therein, a content of the substance to be detected, or the like. For example, a light passing through the portion where there is a droplet and a light passing through the portion without a droplet have different intensities and/or brightness, so that the detection information such as the size and position of the droplet can be obtained.
For example, the micro-total analysis system provided by at least one example of the present disclosure can be applied to fields of biology, medicine, chemistry, or the like to complete parallel experiments and detections, for example, a droplet of blood to be detected is separated into several sub-droplets, and then transported to different positions for simultaneous reaction, different items detected at a same time. The system avoids the construction of a large and complicated experimental system, has a high experiment reproducibility and reduces experiment difficulties. The micro-total analysis system provided by the example of the present disclosure can be used for detection and calibration in physical, biological and chemical fields, such as spectral detection, substance analysis, calibration, molecular diagnostics, food quarantine, bacteria classification, or the like.
For example, the liquid passing through the microfluidic device 10 may be a droplet, a fluid, or the like. Hereinafter, a droplet will be described as an example.
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For example, with the gratings designed differently, the optical unit 20 adjusts light with different wavelengths and different intensities to irradiate the liquid/droplet in the middle microfluidic device or the lower detection unit (for example, a photosensitive sensor of a sensor group). Different gratings can form different light, such that droplets react differently. The grating may be designed as an optical path collimator to improve an irradiation accuracy of the light. The optical unit is integrated to achieve the functions of a spectrometer, a spectrograph, detection light source, or the like.
For example, the light source on one side of the optical unit may be a laser light source, the laser is emitted to the light guide plate, and then lasers of different wavelengths are emitted from the corresponding positions through the gratings which are designed differently at different positions on the light guide plate. The advantage is that using only one laser light source implements the requirements of different laser light sources, and reduces the power consumption. Different sub-droplets are used in different detection items to correspond to different fluorescence detections, saving a light filter which detects one droplet using multiple fluorescences.
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For example, the light source 201 may be a point light source, a surface light source, or a combination of a plurality of point light sources. The light guide plate 202 may be made of glass or other materials. For example, the grating may adopt a holographic grating/micro/nano lens, and may include a horizontal structure and a vertical structure, which can adjust the irradiation direction of the light and control the wavelength of transmitted light. For example, the grating may also be of a planar microstructure, which mainly adjusts the optical path. For example, the grating may be made of a holographic material by an exposure process. The grating structure is not limited in the example of the present disclosure, as long as it may function to adjust the light path and/or the wavelength of the light.
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For example, the optical unit 20 may be separated or integrally fabricated on the microfluidic device 10. For example, as shown in
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For example, for the experiments which may pollute the microfluidic device, the micro-total analysis system may be modularly designed to replace only the middle microfluidic device, further reducing costs.
An electrowetting on dielectric (EWOD) microfluidic device will be described as an example. A digital microfluidic technology based on EWOD refers to such a technology that a contact angle of the droplet on an insulating medium may be changed by applying a voltage signal on the chip with the insulating medium, causing the droplet to deform asymmetrically, thereby generating an internal force to operate the droplet. Due to many advantages of simple implementation, convenient operation, good controllability, and high driving capability, this technology is receiving more and more attention and is considered to be the most promising technology in the field of microfluidics. It should be noted that the type of the microfluidic device 10 is not limited in the example of the present disclosure.
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For example, in a case where the optical unit 20 is integrated in the microfluidic device 10, the grating 203 and the second electrode 122 may be disposed on the second base substrate 121. The grating 203 and the second electrode 122 may be disposed on a same surface of the second base substrate 121 or two opposite surfaces of the second base substrate 121.
For example, in the microfluidic device 10, the first electrode 111 and the second electrode 122 may be made of a transparent conductive material, such as indium tin oxide (ITO), to avoid shielding light. A liquid driving and detection circuit may be fabricated in the microfluidic device 10 or the detection unit 30.
For example, a second hydrophobic layer 123 may be formed on the second electrode 122, and an insulating layer 112 and a first hydrophobic layer 113 may be formed on the first electrode 111.
For example, the electrowetting microfluidic device may be fabricated as follows.
(1) The entire surface of the second electrode 122 is deposited on the second base substrate 121. It may be deposited by plasma enhanced chemical vapor deposition, and the second electrode is a transparent electrode, such as an ITO electrode.
(2) The second hydrophobic layer 123 is fabricated on the second electrode 122.
(3) The first TFT 151 and the first electrode 111 (a driving electrode array) are formed on the first base substrate 101.
(4) The entire surface of the dielectric insulating layer 112 is deposited on the first electrode 111. The dielectric insulating layer may be, for example, SiNx, SiOx or the like.
(5) The first hydrophobic layer 113 is fabricated on the insulating layer 112. The first hydrophobic layer 113 may be a hydrophobic material for the entire surface.
For example, the first hydrophobic layer 113 and the second hydrophobic layer 123 may be applied by a spin-coating process, or a layer of substance, e.g. SiF, is deposited firstly, and then is bombarded by a plasma to generate a low surface energy hydrophobic material. The material and fabricating process of the hydrophobic layer are not limited in the examples of the present disclosure.
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In one example, the detection unit 30 includes a sensor group, but not limited thereto. For example, the sensor group includes at least one of an optical sensor, a capacitive sensor, a temperature sensor, and an ultrasonic sensor. For example, the detection unit 30 (the sensor group) may be separated or integrated. To facilitate the detection, some sensors of the detection unit 30 may be integrated in the base substrate of the microfluidic device. Similarly, a control circuit of the microfluidic device may also be integrally fabricated in the detection unit. For example, the sensor group may perform various detections, such as position detection, temperature detection, optical detection, or the like. For example, the detection unit 30 may also perform detection using technologies such as CCD/CMOS/photomultiplier, or the like.
The optical sensor performs detection by irradiating a photosensitive diode with the light having different light intensities to generate different light currents. The position, shape, volume, or the like of the droplet can be detected by irradiating the photosensitive diode using the light path confined by the light guide plate. The content of different test items may be detected by irradiating the photosensitive diode using fluorescence emitted from a marker in a target cell. For example, the information of the liquid to be detected may be detected, such as composition, content, position, shape, or the like.
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For example, taking a genetic testing as an example, the micro-total analysis system according to one example works as follows. The droplet to be detected in the microfluidic device 10 is divided into several sub-droplets to be transported to different positions. The target cells in the sub-droplets react with the marked cells at the corresponding positions, carrying the marker, such as luciferase or the like. The marker emits different fluorescent photons under the excitation of lasers with different wavelengths. The fluorescence is irradiated on the photoelectric sensor (e.g., a photosensitive diode) to generate a voltage/current signal with a corresponding magnitude, thereby meeting different detection requirements at different positions. The detections with different requirements may be performed in parallel.
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For example, the first gate lines GL are scanned row by row, and data signals are input column by column, thereby individually controlling each photosensitive diode. For example, as shown in
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An example of the present disclosure provides a micro-total analysis system which can drive liquid and detect capacitance in a time-division manner, and can obtain capacitance detection results in real time. As not only electrodes for driving the liquid 131 to be detected, but also the electrodes for capacitance detection, the first electrode 111 and the second electrode 122 are easy to manufacture, and are driven and detected simply.
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For example, the first gate electrodes 1513 of the first TFTs 151 in a same row may be electrically connected, and the first source electrodes 1512 of the first TFTs 151 in a same column may be electrically connected. For example, each of the second gate lines GT is scanned row by row, and the data signals are input column by column, thereby individually controlling each of the first sub-electrodes. For example, as shown in
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For example, the TFTs 151 in a same row are connected to a same second gate line (GT), and the TFTs 151 in a same column are connected to a same second data line (DT).
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An example of the present disclosure provides a micro-total analysis/microfluidic method in which a common signal is input to the second electrode 122 and a first driving signal is input to the first electrode 111 in the first period. For example, the first driving signal may be a direct current signal or an alternating current signal (e.g., a square wave signal).
An example of the present disclosure provides a micro-total analysis/microfluidic method in which a second driving signal is input to the second electrode 122 and the first electrode 111 is floated in the second period. For example, the second driving signal may be a direct current signal or an alternating current signal (e.g., a square wave signal).
An example of the present disclosure provides a microfluidic method, and in order to control the liquid/droplet to be detected in real time, the microfluidic method further includes a step of adjusting the driving signal in real time based on a result of the capacitance detection.
For example, in a droplet driving phase (the first period T1), the second electrode 122 (all of the second sub-electrodes 1221) is provided with a common ground signal V1 (a reference voltage terminal), and the first sub-electrode 1111 is selected by the TFT as needed to provide the first driving signal V2 selectively. The function of the first driving signal V2 is to control the operations of moving, separating and combining droplets, or the like. The first driving signal V2 may be a DC signal or an AC square wave signal. For example, if the first driving signal V2 is a DC signal, the DC signal is required to be always supplied in the driving phase, and the power consumption is higher. For example, if the first driving signal V2 is an AC square wave, the voltage will be stored on CL (CL is an equivalent total capacitance of a dielectric layer between a upper sub-electrode and a lower sub-electrode, and the droplet) in a high-level phase, and the first TFT is turned off in a low-level phase. However, due to the leakage current of the first TFT, the stored voltage will leak bit by bit, resulting in a decrease in driving capability. Therefore, the adoption of the driving mode of the AC square wave not only saves power consumption but also ensure the driving effect. In addition, the AC signal driving helps to reduce contact angle hysteresis and surface ion adsorption, etc., and to achieve a better EWOD effect. For example, the first driving signal V2 (AC driving signal) has a frequency greater than a resonance frequency of the droplet and less than a charging frequency of the device, thereby obtaining a good electrowetting effect.
For example, in the droplet detecting phase (the second period T2), the second driving signal (for example, a square wave signal) may be input to the second electrode 122/second sub-electrode 1221, and the first sub-electrode 1111 is floating (Vf). The sensing capacitance is generated, and the magnitudes of the sensing capacitances at locations with the droplet and without the droplet are different. The sensing capacitance of the first sub-electrode 1111 is read out one by one through gating of the first TFT. For example, a positional shape diagram of the droplet can be obtained by the read-out sensing capacitance, and the information of the droplet, such as volume, size, or the like, may be calculated by a corresponding algorithm.
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For example, the thermistor 161 may replace the third TFT 153 to sense the temperature when the driving signal is a high-voltage signal. For example, when the temperature sensed by the thermistor 161 decreases, the resistance of the thermistor increases, and a sensing current output by the third TFT 153 decreases; and when the temperature sensed by the thermistor 161 increases, the resistance of the thermistor decreases, and the sensing current output by the third TFT 153 increases.
For example, the genetic testing is required to be performed in a stable temperature environment, and the temperature sensor can detect and regulate the temperature of an operating environment in real time.
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An example of the present disclosure provides a micro-total analysis method, including: accommodating a liquid to be detected in a microfluidic device, forming a first light irradiated to the microfluidic device, and detecting the liquid to be detected and outputting a detection signal to obtain detection information.
An example of the present disclosure provides a micro-total analysis method. The microfluidic device includes a first electrode disposed on a first base substrate and a second electrode disposed on a second base substrate, the second electrode is insulated from the first electrode, driving and capacitance detection performed in a time-division mode, and the micro-total analysis method includes: driving the liquid with the first electrode and the second electrode in a first period; and outputting a capacitance signal between the first electrode and the second electrode in a second period.
In the micro-analysis method according to an example of the present disclosure, in the first period, a common signal is input to the second electrode and a first driving signal is input to the first electrode. The micro-total analysis method further includes a step of adjusting the first driving signal in real time based on the result of the capacitance detection.
For example, the micro-total analysis method includes a plurality of time spans TE, each of which includes the first period T1 and the second period T2, and the first period T1 is a driving phase and the second period T2 is a detecting phase. The first driving signal input to the first electrode in a subsequent time span TE may be adjusted in real time according to the result of the capacitance detection in a previous time span TE that before the subsequent time span TE, thereby realizing a real-time adjustment and detection.
For example, the liquid to be detected generates fluorescence under excitation of the first light, and the detection unit is irradiated with the fluorescence and outputs the detection signal according to the fluorescence. Certainly, the detection unit is not limited to detecting the fluorescence. For example, the detection unit may also detect transmitted light transmitting through the liquid to be detected to achieve the detection purpose.
The two above-mentioned examples provide the micro-total analysis method. For details, please refer to the driving method of the capacitive sensor described above, and details are not described herein again.
In the examples of the present disclosure, the optical sensor, the capacitance sensor, and the temperature sensor may be provided with respective TFTs, gate lines, and data lines to reduce the number of leading wires of each type of sensors, but not limited thereto. The detection method may be optical, capacitive, impedance, or the like.
It should be noted that, in order to clearly illustrate, a layer or an area may be amplified in the drawings of the examples of the present disclosure. It is to be understood that, when a member such as a layer, a film, an area or a substrate is located or disposed on or below another member, the member can be located or disposed on or below the another member directly, or an intermediate member or intermediate member(s) can be disposed.
In addition, the features in different examples or different features in the same examples can be combined without conflict.
What have been described above are only specific implementations of the present disclosure, the protection scope of the present disclosure is not limited thereto. Any modifications or substitutions easily occur to those skilled in the art within the technical scope of the present disclosure should be within the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be based on the protection scope of the claims.
Number | Date | Country | Kind |
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201710797437.6 | Sep 2017 | CN | national |
Filing Document | Filing Date | Country | Kind |
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PCT/CN2018/100834 | 8/16/2018 | WO |
Publishing Document | Publishing Date | Country | Kind |
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WO2019/047702 | 3/14/2019 | WO | A |
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