Portable Diagnostic Device and Method Thereof

Abstract

A method and a portable diagnostic device (20) for detecting at least one analyte from a sample using a microfluidic cartridge (22). The portable diagnostic device (20) includes a cartridge receiving unit, a cartridge driving unit (30), and an optical unit (32). A method and a device for obtaining prevalence information, which includes at least one of the portable diagnostic devices (20). A method and a system for managing a network of portable diagnostic devices and obtaining prevalence information, which includes at least one of the portable diagnostic devices (20). A diagnostic system having a plurality of automated features and capable of providing a one-step solution for near-patient clinical assessment and diagnosis.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62722174, filed on Aug. 23, 2018, which is hereby incorporated by reference in its entirety.

[0003] This application relates to PCT Application No. PCT / CN2015 / 0700567, filed on Aug. 5, 2015, the content of which is hereby incorporated by reference in its entirety. Technical Field

[0004] The present invention relates to a system for detecting an analyte and a method of using the same. More specifically, the present invention relates to a microfluidic cartridge and an apparatus for such a microfluidic cartridge. Background Art

[0005] Traditional diagnosis, screening, disease staging, veterinary, drug testing, etc. are typically performed in a laboratory and the tests are often time-consuming, expensive and require many resources, supplies and support. Current systems require multiple steps between initial sample collection and receipt of a diagnostic result. They require a high degree of human involvement and are thus prone to human error. In some models, reagents are added manually by the user, which means that potential reagent spills can pose health and safety risks to the user. In certain models, diagnostic tests involve multiple manual steps, such as loading reagents. Finally, in some models, the results are interpreted by the user, which can lead to discrepancies and even potential misunderstandings. Summary of the Invention

[0006] In view of the foregoing background art, an object of the present invention is to provide an improved diagnostic system for detecting one or more analytes.

[0007] According to one aspect, the diagnostic system comprises two parts: an apparatus for detecting at least one or more analytes and a microfluidic cartridge.

[0008] In some embodiments, the diagnostic system is a portable and stand-alone system for detecting an analyte. In some embodiments, the diagnostic system performs at least one immunoassay. In some embodiments, the diagnostic system performs at least one immunofluorescence assay. In some embodiments, the device includes a microfluidic cartridge drive unit, an optical inspection unit, as well as a control unit and a power supply unit. In some embodiments, the device can run the binding and detection of the analyte without any fluid interface with an instrument. In some embodiments, the microfluidic cartridge holding unit holds a microfluidic cartridge that holds a microarray and an integrated microfluidic chip. In some embodiments, the microfluidic cartridge holds a sample containing the analyte and performs different process steps in the detection of the analyte. In some embodiments, all process steps, including the reaction of the analyte on the microarray, the detection of the signal, the analysis of the data, and the display of the results, are automatically performed by the device on a single tray without any user intervention. It only takes a few minutes to completely detect the analyte using the present invention.

[0009] On the one hand, a portable diagnostic device is provided for detecting at least one analyte from a sample using a microfluidic cartridge. The microfluidic cartridge has a plurality of micropumps, a plurality of reservoirs connected via microchannels to at least one diagnostic section, and a plurality of microvalves for sealing the fluid in the reservoirs to prevent it from flowing into the reaction site. The portable diagnostic device includes a cartridge holding unit, a cartridge drive unit, and an optical unit. The cartridge holding unit is configured to hold the microfluidic cartridge. The cartridge drive unit includes: a) a microvalve controller configured to control the microvalves, and b) a micropump controller configured to actuate the micropumps. When the microfluidic cartridge is placed in the cartridge holding unit, the micropump controller and the microvalve controller can cooperate to actuate the fluid to flow from the reservoirs to the diagnostic section in a predetermined order. When the microfluidic cartridge is placed in the cartridge holding unit, the optical unit is aligned with the diagnostic section. The portable diagnostic device can control and monitor the reaction within the microfluidic cartridge.

[0010] In some embodiments, the microvalve controller includes at least one heating element configured to apply thermal energy to a thermally deformable surface of the at least one microvalve to open the microvalve.

[0011] In some embodiments, when the cartridge is placed in the cartridge holding unit, the at least one heating element is juxtaposed with at least one microvalve of the microfluidic cartridge.

[0012] In some embodiments, the heating element is an infrared emitter.

[0013] In some embodiments, the micropump controller includes at least one electrical connector for electrically connecting to the at least one micropump of the microfluidic cartridge and is configured to supply current to the at least one micropump.

[0014] In some embodiments, the optical unit includes an illumination assembly and a sensor assembly. The illumination assembly is configured to transmit light to a diagnostic portion of the microfluidic cartridge. The sensor assembly is configured to detect at least one signal generated by the diagnostic portion due to the presence of an analyte when the microfluidic cartridge is inserted and operated under predetermined conditions.

[0015] In some embodiments, the illumination assembly includes a light source having a wavelength in the range of 600 nm to 650 nm, and the at least one data signal is a fluorescence signal.

[0016] In some embodiments, the portable diagnostic device further includes a control unit configured to perform one or more of the following: a. providing a predetermined sequence to a cartridge drive unit to direct the movement of at least one fluid within the microfluidic cartridge; b. providing predetermined conditions to the optical unit to perform quantitative and / or qualitative analysis of the analyte; c. storing the data signal obtained from the optical unit; and d. controlling and monitoring the operation of the portable diagnostic device.

[0017] In some embodiments, the control unit is configured to provide a predetermined sequence to the cartridge drive unit and predetermined conditions to the optical unit based on the identification of the microfluidic cartridge.

[0018] In some embodiments, the portable diagnostic device further includes a housing for anchoring the cartridge receiving unit, the cartridge drive unit, and the optical unit therein.

[0019] The cartridge receiving unit further includes a track assembly and a tray. The track assembly includes a pair of slidable tracks. The tray is configured to receive the microfluidic cartridge and is anchored on the pair of tracks. The tracks may slide the tray into and out of the housing such that the microfluidic cartridge can be inserted into the housing.

[0020] In some embodiments, the track assembly of the cartridge receiving unit, the cartridge drive unit, and the optical unit are mounted within the housing in a configuration such that when the microfluidic cartridge is inserted into the portable diagnostic device, there is a space for receiving the microfluidic cartridge, the space including one or more microvalve positions, one or more micropump positions, and reaction positions corresponding respectively to the positions of one or more microvalves, one or more micropumps, and reaction sites when the microfluidic cartridge is inserted into the space. The heating element of the microvalve controller is mounted near the microvalve position, where heat can be directed to the microvalve on the microfluidic cartridge when the microfluidic cartridge is inserted. One or more electrical connectors of the micropump controller are mounted side by side with one or more micropumps to be electrically connected to the at least one micropump when the microfluidic cartridge is inserted into the portable diagnostic device.

[0021] In some embodiments, the optical unit includes an illumination assembly, the illumination assembly including a light source and a sensor assembly, the sensor assembly including a light sensor. The light source and the light sensor are mounted to point at the diagnostic portion of the microfluidic cartridge.

[0022] In some embodiments, the portable diagnostic device further includes a built-in or removable rechargeable battery.

[0023] In some embodiments, the portable diagnostic device further includes a switch to trigger the identification unit to read the identification of the microfluidic cartridge when the microfluidic cartridge is positioned in a designated area.

[0024] In some embodiments, the portable diagnostic device does not include any means for actuating fluids external to the microfluidic cartridge, and wherein the portable diagnostic device does not provide any reagents.

[0025] In some embodiments, the portable diagnostic device further includes a user interface unit configured to display a quantitative and / or qualitative analysis of the analyte, wherein the user interface unit is connected to the control unit.

[0026] In some embodiments, the cartridge receiving unit and the cartridge driving unit are configured to connect to the microfluidic cartridge when the microfluidic cartridge is fixed at a designated area. The cartridge receiving unit receives and fixes the microfluidic cartridge at the designated area. The microvalve controller is juxtaposed with at least one microvalve. The micropump controller is electrically connected to at least one micropump. Fluid actuation and analyte detection are performed within the designated area during operation.

[0027] In some embodiments, the cartridge receiving unit includes a rail assembly and a tray. The rail assembly includes a cavity for slidably receiving the tray. The tray includes a cartridge chamber for receiving the microfluidic cartridge such that the microfluidic cartridge is positioned at the designated area.

[0028] In some embodiments, the portable diagnostic device further includes at least one of the following sensors controlled by a controller: a. a humidity sensor; b. a temperature sensor; such that one or more environmental data can be collected when the microfluidic cartridge is used in the device.

[0029] In some embodiments, the portable diagnostic device further includes a data storage module for storing one or more of environmental data and diagnostic data; and a transmitter for transmitting environmental data and diagnostic data to a remote server.

[0030] In some embodiments, the portable diagnostic device further includes a smart device, wherein the smart device includes: a. an environmental measurement module for acquiring environmental data, wherein the environmental data includes at least one environmental parameter at the location; b. a data storage module for storing raw data, wherein the raw data includes one or more of environmental data and diagnostic data; and c. a transmitter for transmitting the raw data to a remote server.

[0031] In some embodiments, the environmental data is selected from location data, humidity, temperature, and time.

[0032] In some embodiments, the intelligent device may optionally be connected to and communicate with a portable diagnostic device and a remote server.

[0033] In some embodiments, the intelligent device further includes a battery, wherein the battery is rechargeable and can operate for 30 days without being charged.

[0034] According to another aspect, a microfluidic cartridge is provided, which includes a microfluidic section and a diagnostic section. The microfluidic section includes: i. a plurality of reservoirs capable of holding fluids therein; ii. a plurality of microchannels connecting one or more reservoirs to the diagnostic section; iii. a plurality of microvalves operable between a closed state and an open state to seal and open the microchannel connections respectively; and iv. a plurality of micropumps coupled to one or more reservoirs. The microvalves in the closed state allow the fluids to be stored and sealed within the reservoirs, while the microvalves in the open state allow the fluids to flow between the reservoirs and the diagnostic section. The micropumps can be actuated to move the fluids from the reservoirs to the diagnostic section, such that a variety of reagents can be pre-loaded and stored in the microfluidic cartridge in a sealed manner until use.

[0035] In some embodiments, the diagnostic section includes a diagnostic chamber for receiving at least one fluid from the microfluidic section.

[0036] In some embodiments, the microfluidic cartridge further includes a waste reservoir connected to the diagnostic section via an outlet to receive the waste fluid ejected from the diagnostic chamber.

[0037] In some embodiments, the diagnostic section is at least partially transparent for optical detection.

[0038] In some embodiments, the microfluidic cartridge further includes a microporous membrane configured to remove gases in the sample and / or reagent.

[0039] In some embodiments, the waste reservoir is connected to the microporous membrane to remove gases from the waste.

[0040] In some embodiments, at least one reservoir is filled with at least one fluid, wherein the fluid is a reagent and is sealed shut with a microvalve.

[0041] In some embodiments, the microfluidic cartridge further includes a variety of reagents pre-loaded, sealed, and stored in the reservoirs respectively; and at least one reactant pre-supplied at the diagnostic section.

[0042] In some embodiments, at least one reservoir for holding at least one sample further includes a sample inlet with a detachable cap.

[0043] According to another aspect, there is provided a portable diagnostic system that includes a portable diagnostic device as described herein and optionally includes a microfluidic cartridge as described herein.

[0044] According to another aspect, there is provided a method of detecting at least one analyte from a sample using a portable diagnostic device as described above. The sample is loaded onto a microfluidic cartridge that has a diagnostic portion and a microfluidic portion, the diagnostic portion including at least one pre-supplied reactant, and the microfluidic portion including a plurality of microvalves, a plurality of micropumps, and a plurality of reservoirs including at least one pre-supplied reagent. The microfluidic cartridge is positioned at a diagnostic designated area of a cartridge receiving unit. The method includes the steps of: a) guiding the sample and at least one reagent from the microfluidic portion to the diagnostic portion in a predetermined order within the microfluidic cartridge by opening at least one microvalve that seals at least one reservoir of the microfluidic cartridge and actuating at least one micropump in the microfluidic cartridge; b) providing a predetermined condition to the diagnostic portion of the microfluidic cartridge to generate at least one signal; c) detecting the at least one data signal using an optical sensor and collecting diagnostic data; and d) analyzing the diagnostic data to quantitatively and / or qualitatively determine the presence of the analyte.

[0045] In some embodiments, it further includes the steps of: a) reading the identification of the microfluidic cartridge; b) providing a predetermined order to a cartridge drive unit based on the identification of the microfluidic cartridge and providing a predetermined condition to an optical unit.

[0046] According to another aspect, there is provided a method of obtaining prevalence information, which includes: a. obtaining diagnostic data or a sample at a certain location using the portable diagnostic device according to claim 20, wherein the diagnostic data includes at least one biochemical or pathological measurement value of a subject; b. obtaining environmental data at the location; c. transmitting the diagnostic data and the environmental data to a server; d. in the server, collecting and storing the diagnostic data and the environmental data of a plurality of subjects at a plurality of locations to form a database; and e. analyzing the prevalence information of the subjects at the plurality of locations in the database.

[0047] According to another aspect, a system for managing a network of portable diagnostic devices includes at least one portable diagnostic device as described herein, at least one user terminal, and a server. The server includes a data module for collecting and storing raw data, wherein the raw data includes one or more of the following: (1) diagnostic data obtained at a certain location using a portable diagnostic device, wherein the diagnostic data includes at least one biochemical or pathological measurement value of a subject, (2) environmental data obtained at the location using an environmental measurement module, wherein the environmental data includes at least one environmental parameter, and (3) device data obtained from the portable diagnostic device, and (4) a data module for analyzing the raw data. The server is connected to the user terminal and the portable diagnostic device.

[0048] In some embodiments, the system further includes a plurality of portable diagnostic devices, wherein the server is a cloud-based platform wirelessly connected to the user terminal and the portable diagnostic devices.

[0049] In some embodiments, the data module performs one or more of the following steps: (1) collecting raw data; (2) analyzing the raw data to provide results; and (3) transmitting the results to the user terminal. The data module also provides one or more of the following results: (1) prevalence rates at different locations shown on a map; (2) prevalence rates over a period of time; and (3) severity of a disease in a specific location; and (4) correlation between environmental conditions and device status.

[0050] In some embodiments, the data module further includes one or more access controls for the raw data and the results.

[0051] In some embodiments, the server remotely provides technical support or one or more software updates. For example, the server can transmit an updated version of the device software via a network. The server can also provide information on how to resolve specific machine errors of the device. In some embodiments, the data module can evaluate information on environmental parameters of the device, such as temperature, humidity, time, and location data (e.g., position), and compare it with the error code received by the device to determine whether one or more environmental parameters caused the error code. The data module can provide a solution in the form of remote technical support to the user, instructions on how to solve the problem, or other forms of technical support. The data module can also remotely send software updates to the smart device.

[0052] In some embodiments, the data module further provides a correlation between environmental conditions and prevalence rates. In some embodiments, the environmental conditions include temperature, humidity, or time. In some embodiments, the environmental conditions are determined by a third-party source rather than by the portable diagnostic device.

[0053] In some embodiments, the data module further includes one or more access controls for the raw data and the results.

[0054] According to another aspect, a method of using the system described herein is provided, which includes the following steps: (1) obtaining the raw data at the location and storing it on the data storage module; (2) transferring the raw data from the data storage module to the server; (3) in the server, collecting and storing multiple raw data from multiple portable diagnostic devices to form a database; (4) analyzing the database to provide a result. The raw data includes one or more of the following: (1) diagnostic data obtained at a location using a portable diagnostic device, where the diagnostic data includes at least one biochemical or pathological measurement of a subject; (2) environmental data obtained at the location using an environmental measurement module, where the environmental data includes at least one environmental parameter; (3) device data obtained from the portable diagnostic device.

[0055] In some embodiments, the raw data is transferred to the server once an hour even when the portable diagnostic device is not connected to an external power source.

[0056] In some embodiments, the raw data is diagnostic data obtained at a location using a portable diagnostic device, where the diagnostic data includes at least one biochemical or pathological measurement of a subject and location data; and the result provides prevalence information.

[0057] In some embodiments, the raw data is one or more of temperature, humidity, time, location data, and device data; and the result provides information associated with the performance of the portable diagnostic device. In some embodiments, the performance of the portable diagnostic device is indicated by an operating state, such as an error code of the machine, system voltage, total operating hours, and total number of tests. The result includes but is not limited to error codes, ways to fix the error codes, and correlations between the error codes and one or more of temperature, humidity, location data, and time.

[0058] Various embodiments of the present disclosure have many advantages, such as providing a "one-step" solution for on-site detection of analytes. For example, some embodiments provide a diagnostic system with multiple automated features that can provide a one-step solution for near-patient clinical assessment and diagnosis.

[0059] In some embodiments, the diagnostic system is portable and requires minimal user intervention. Near-patient testing can be performed by medical professionals (e.g., physicians and nurses) or trained non-professionals (e.g., clinic staff and caregivers).

[0060] Exemplary devices for detecting analytes involve relatively small amounts or volumes of sample (in some embodiments, a few microliters (μl) to several hundred μl), while using integrated reaction-to-detection instrumentation / methods. Thus, this is a true "point-of-care device" that will provide real convenience to field personnel. As a result, the special handling and transportation of the analyte to a laboratory and the excessive transportation time that may affect the quality of the analyte are greatly reduced.

[0061] Another advantage is that, compared to conventional diagnostic methods or systems, the devices of some embodiments require little or no sample preparation, thus reducing processing time.

[0062] Another advantage of some embodiments is that it can be applied to various fields of diagnostics and food safety analysis. For example, a method of detecting one or more analytes associated with the presence of a disease in a subject. This application includes but is not limited to animal immuno-diagnostics (e.g., swine influenza virus (e.g., H1N1) infection, porcine reproductive and respiratory syndrome (PRRS), foot-and-mouth disease (FMD) in cattle, classical swine fever (CSFV) infection, and bovine spongiform encephalopathy (BSE) infectious diseases), food safety testing (e.g., detection of food allergens (e.g., peanuts, seafood), aflatoxin, and melamine), clinical testing of human subjects (e.g., infectious diseases (e.g., sexually transmitted diseases (STD), Middle East respiratory syndrome coronavirus (MERS-CoV), and influenza virus infection), tropical diseases (e.g., dengue virus and Japanese encephalitis virus infection), and emerging infectious diseases belonging to the antigen / antibody immune mechanism in their pathological pathways), detection of influenza A, influenza B, RSV, HPIV, adenovirus, dengue, chikungunya, Zika, malaria, leptospirosis, toxoplasmosis, canine distemper virus Ab, canine parvovirus Ab, or heartworm. Some embodiments can be adapted to analyze multiple analytes in the same sample and the same process, thus significantly reducing the cost and processing time involved in examining multiple diseases / analytes.

[0063] Exemplary embodiments are specifically configured to enable all required steps to be performed on a single tray without user intervention. These steps include (1) reaction in a microfluidic cartridge, (2) detection of signals from the microfluidic cartridge, and (3) analysis of the results and display them to the user. They provide an automated rapid diagnostic device that minimizes the possibility of human-machine interaction and human error. It provides a one-step foolproof solution for near-patient rapid diagnosis that can be used by minimally trained non-professionals.

[0064] In some exemplary embodiments (e.g., a micro-valve controller), the actuation assembly provides a sealed compartment for storing at least one reagent in a reservoir and actively and precisely actuating at least one fluid within the microfluidic cartridge.

[0065] For some exemplary embodiments (e.g., single tray systems), reactions and detections can be performed in the same cartridge without separating the diagnostic portion from the detection portion. The microfluidic cartridge (e.g., for pre-loaded chip embodiments) is self-contained, i.e., all reagents required for reactions during the manufacturing process are pre-supplied (or pre-loaded) within the microfluidic cartridge, such that no reagents are required on-site.

[0066] In summary, the various embodiments provide various advantages such as low cost, time and space savings, portability, requiring minimal resources, and enabling rapid, large-scale, and on-site effective complete analyte detection with a low level of skills and technicians. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Figure 1 is a block diagram showing a diagnostic system according to an embodiment of the present invention.

[0068] Figure 2 is a schematic diagram of a diagnostic system according to an exemplary embodiment of the present invention.

[0069] Figure 3 is a schematic bottom view of a tray of a diagnostic system with (right) and without (left) a diagnostic chip according to an exemplary embodiment of the present invention.

[0070] Figure 4 is a schematic diagram of a fluid control component of a microfluidic cartridge operation unit of a device according to an exemplary embodiment of the present invention.

[0071] Figure 5 is a schematic diagram of an optical inspection unit of a diagnostic system according to an exemplary embodiment of the present invention.

[0072] Figure 6A is a schematic top view (left), side view (middle), and bottom view (right) of a microfluidic cartridge according to an exemplary embodiment of the present invention.

[0073] Figure 6B is a schematic exploded view of a microfluidic cartridge according to an exemplary embodiment of the present invention; Figure 6C is a schematic exploded view of a microfluidic cartridge according to another exemplary embodiment of the present invention.

[0074] Figure 7 is a flowchart of a production sequence of a microfluidic cartridge according to another exemplary embodiment of the present invention.

[0075] Figure 8 is a flowchart of a coating process and deposition of detection points on a diagnostic chip according to an embodiment of the present invention according to another exemplary embodiment of the present invention.

[0076] Figure 9 Depicts the detection of a fluorescent antigen (FluA) according to an exemplary embodiment of the present invention.

[0077] Figure 10A Is a block diagram of a portable diagnostic device according to an exemplary embodiment of the present invention.

[0078] Figure 10B Is a block diagram of a portable diagnostic device according to another exemplary embodiment of the present invention.

[0079] Figure 11A Is a schematic top view (left), side view (middle), and bottom view (right) of a microfluidic cartridge according to an exemplary embodiment of the present invention.

[0080] Figure 11B Is according to Figure 11A A schematic exploded view of the microvalve membrane and the top portion of a microfluidic cartridge according to an exemplary embodiment of the present invention as shown in

[0081] Figure 11C Is according to Figure 11A A schematic exploded view of a microfluidic cartridge according to an exemplary embodiment of the present invention as shown in

[0082] Figure 12A Is a schematic exploded view of a microfluidic cartridge according to another exemplary embodiment of the present invention.

[0083] Figure 12B Is according to Figure 12A A schematic top view of the microvalve membrane of a microfluidic cartridge according to an exemplary embodiment of the present invention as shown in

[0084] Figure 12C Is according to Figure 12A A schematic top view of the top portion of a microfluidic cartridge according to an exemplary embodiment of the present invention as shown in

[0085] Figure 12D Is according to Figure 12A A schematic bottom view of the top portion of a microfluidic cartridge according to an exemplary embodiment of the present invention as shown in

[0086] Figure 12E Is according to Figure 12A A schematic top view of the bottom portion of a microfluidic cartridge according to an exemplary embodiment of the present invention as shown in

[0087] Figure 12F Is according to Figure 12A A schematic bottom view of the bottom portion of a microfluidic cartridge according to an exemplary embodiment of the present invention as shown in

[0088] Figure 13A And 13B is a schematic diagram of fluid movement within a microfluidic cartridge driven by a cartridge drive unit according to an exemplary embodiment.

[0089] Figure 14A is a schematic exploded view of a portable diagnostic device according to an exemplary embodiment of the present invention.

[0090] Figure 14B is a schematic exploded view of another example of a portable diagnostic device.

[0091] Figure 15A is a top perspective view of a microvalve controller of a microfluidic cartridge drive unit according to an exemplary embodiment of the present invention.

[0092] Figure 15B is the same as that shown in Figure 15A a bottom perspective view of the microvalve controller.

[0093] Figure 16A and Figure 16B is a schematic diagram of a microfluidic cartridge receiving unit according to an exemplary embodiment of the present invention.

[0094] Figure 16C is the same as that shown in Figure 16A a schematic diagram of a tray of the microfluidic cartridge receiving unit.

[0095] Figure 16D is the same as that shown in Figure 16C a schematic diagram of the same tray but with a microfluidic cartridge inserted therein.

[0096] Figure 17 is an exploded view of an optical unit and an identification unit of a diagnostic device according to an embodiment of the present invention.

[0097] Figure 18 is a schematic diagram of an assembly of an optical unit, an identification unit, a cartridge drive unit, and a cartridge receiving unit of a diagnostic device according to an exemplary embodiment of the present invention.

[0098] Figure 19 is a flowchart of the operation of a diagnostic device according to an exemplary embodiment of the present invention.

[0099] Figure 20 is a schematic diagram of a system for managing a network of point-of-care diagnostic devices and obtaining prevalence or other information according to an embodiment of the present invention.

[0100] Figure 21 is a flowchart of a method for obtaining prevalence or environmental information according to an embodiment of the present invention.

[0101] Figure 22 is a flowchart of the operation of a system according to an embodiment of the present invention Figure 20 of the system.

[0102] Figure 23 is a flowchart showing information and data flow of various components of a system according to an embodiment of the present invention.

[0103] Figure 24 is a schematic diagram of a combination of an intelligent device and a unit interacting therewith according to an embodiment of the present invention. Detailed Description

[0104] As used herein and in the claims, "comprising" means including the following elements, but not excluding other elements.

[0105] As used herein and in the claims, "coupled" or "connected" means a connection made directly or indirectly via one or more physical means, unless otherwise specified.

[0106] As used herein and in the claims, "microfluidics" refers to the precise control and manipulation of fluids or liquids that are geometrically confined to a smaller sub-millimeter scale, at which capillary infiltration controls mass transport to less than 0.01 ml. The microfluidic systems disclosed herein do not include paper-based microfluidic systems. A "microfluidic cartridge" refers to a cartridge having a microfluidic structure that includes fluid connections and various components, modules, chambers, etc. configured to process fluid samples. The microfluidic cartridges disclosed herein perform biological or biochemical assays, such as immunoassays. The microfluidic cartridges disclosed herein do not include applications for polymerase chain reaction (PCR) or nucleic acid sequencing. An "immunoassay" refers to a test involving the conjugation of an antibody or antigen to a molecule to detect an analyte. The molecule can be a molecule that can generate a fluorescent signal or other detection signal.

[0107] A "sample" refers to a substance to be tested and includes, but is not limited to, blood samples, serum samples, urine samples, sweat samples, saliva samples, tear samples, nasal swabs, nasopharyngeal swabs, or samples including other body fluids or other non-human samples. In some embodiments, the sample is processed such that it can be tested by a microfluidic system. For example, a solid sample can be treated with a buffer or other reagent to separate or extract the target analyte.

[0108] As used herein and in the claims, an "analyte" refers to, but is not limited to, pathogens and biomolecules present in, for example, body fluids, nasal swabs, or serum samples from a target individual (including, but not limited to, an animal or human subject). It should be understood that when the term "analyte" is used, it can refer to one or more analytes.

[0109] As used herein and in the claims, "reactant" refers to, but is not limited to, a target substance that reacts with one or more analytes (e.g., an antibody or an antigen). This substance can be immobilized for use on a diagnostic chip. It should be understood that when the term "reactant" is used, it can refer to one or more reactants.

[0110] As used herein and in the claims, "fluid" refers to any liquid, including but not limited to a liquid sample, a reagent, a buffer.

[0111] As used herein and in the claims, "diagnosis" refers to the detection of analytes (not limited to one or more disease-related analytes). However, the diagnostic system described herein does not include the amplification of nucleic acids, such as polymerase chain reaction (PCR) or nucleic acid sequencing.

[0112] As used herein and in the claims, "pre-supplied" or "pre-loaded" refers to a fluid (e.g., a reagent and / or a reactant) that is supplied or loaded during the manufacturing process of a microfluidic cartridge, such that the user does not need to supply or load a liquid.

[0113] As used herein and in the claims, "micro pump" refers to a fluid actuator that actuates at least one fluid.

[0114] As used herein and in the claims, "micro valve" refers to a barrier between channels and / or reservoirs. In some exemplary embodiments, the micro valve is a closed valve in a stationary position and can be opened under active operation, such that a fluid or a reagent can be pre-sealed in a reservoir for long-term storage.

[0115] It will be understood that although the terms first, second, third, etc. may be used herein to describe various limitations, elements, components, regions, layers, and / or sections, these limitations, elements, components, regions, layers, and / or sections should not be limited by these terms. These terms are only used for distinguishing one limitation, element, component, region, layer, or section from another limitation, element, component, region, layer, or section. Thus, without departing from the teachings of the present application, the first limitation, element, component, region, layer, or section discussed below may be referred to as the second limitation, element, component, region, layer, or section.

[0116] It will be further understood that when an element is referred to as being “on another element” or “connected” or “coupled” to another element, it can be directly on or above the other element, or connected or coupled to the other element, or intervening elements may be present. In contrast, when an element is referred to as being “directly on another element” or “directly connected” or “directly coupled” to another element, no intervening elements are present. Other words used to describe the relationship between elements (e.g., “between” and “directly between,” “adjacent” and “directly adjacent,” etc.) should be interpreted in a similar manner. When an element is referred to as being “above another element” herein, it can be above or below the other element, and can be directly coupled to the other element, or intervening elements may be present, or the elements may be separated by a void or gap.

[0117] It will be further understood that when elements are referred to as “top” or “bottom,” these terms are used to describe the relative positions between the elements. Thus, without departing from the teachings of the present application, the “top” portions, elements, components, regions, layers, or sections discussed below can be referred to as “bottom” portions, elements, components, regions, layers, or sections.

[0118] Example 1

[0119] 1. Device

[0120] Figure 1 and Figure 2 illustrates a diagnostic system that includes (1) a diagnostic device 20 and (2) a microfluidic cartridge 22 that operates with the diagnostic device 20. The microfluidic cartridge 22 that includes a microfluidic chip 24 and a diagnostic chip 26 is configured to collect and manipulate at least one sample that may contain at least one analyte. The microfluidic cartridge 22 also houses and / or holds at least one reagent. The diagnostic device 20 is a portable, hand-held, and compact device that includes a control unit 28, a microfluidic cartridge drive unit 30, an optical inspection unit 32, and a display unit 34. The control unit 28 controls and is connected to the microfluidic cartridge drive unit 30, the optical inspection unit 32, and the display unit 34. The microfluidic cartridge drive unit 30 is configured to house and drive the microfluidic cartridge 22 such that the collected sample and reagent pass through the microfluidic chip 24 and the diagnostic chip 26 in a predetermined order. After reacting in a predetermined order, the microfluidic cartridge drive unit 30 also allows inspection or analysis of the diagnostic chip at the same location on the same microfluidic cartridge. The optical inspection unit 32 is configured to inspect the diagnostic chip 26 at the same location on the same microfluidic cartridge where the reaction also occurs to analyze the presence of the analyte. The display unit 34 is configured to display relevant information including the analysis / diagnosis result to the user. Figure 2It is shown that the control unit 28, the microfluidic cartridge driver unit 30, the optical inspection unit 32, the display unit 34, and the power supply unit 65 are encapsulated in a stand-alone diagnostic device. In one exemplary embodiment, the device includes a microfluidic cartridge receiving hole on its front panel for receiving the microfluidic cartridge 22.

[0121] 1.1 Microfluidic Cartridge Driver Unit

[0122] 1.1.1 Tray and Cartridge Chamber

[0123] The microfluidic cartridge driver unit includes a tray 52 and a cartridge chamber 42 (see Figure 3 ).

[0124] The cartridge chamber 42 is configured to receive the microfluidic cartridge 22. The tray 52 includes the cartridge chamber 42 that houses the microfluidic cartridge 22. The tray 52 serves as the same location for performing: (1) reactions to be run in a predetermined order and (2) inspection and analysis of the diagnostic chip. In another exemplary embodiment, the electrical connector 44 is located below the microfluidic cartridge 22 and serves as an interface for the microfluidic cartridge 22 to drive / control power / current and supply it to the microfluidic cartridge 22.

[0125] The single-tray system eliminates the possibility of human error by design. Figure 3 An empty tray (left) and a tray (right) assembled with the microfluidic cartridge 22 are shown.

[0126] The microfluidic cartridge 22 and the cartridge chamber 42 are configured such that the microfluidic cartridge 22 can be assembled into the cartridge chamber 42 and the tray 52 in only one possible way, and thus eliminates the possibility of placing the diagnostic chip 26 of the microfluidic cartridge 22 in an undesired orientation or position.

[0127] In one exemplary embodiment, the tray does not have an anchoring system and has a tolerance of >0.5 mm. The microarray is physically small, and the camera captures a small area (about 2x3 mm 2 ).

[0128] In one exemplary embodiment, an anchoring system is added to the tray 52 to ensure that the diagnostic chip is fixed in the tray 52. In another exemplary embodiment, the anchoring system consists of two anchoring clips positioned orthogonally to each other. Once the diagnostic chip is placed in the tray, the two anchoring clips work together to greatly limit the movement of the diagnostic chip. Less movement means less variation in the possible positions of the biometric, thus increasing the detection accuracy and precision. The addition of the extra anchoring clips reduces the tolerance to 0.1 mm and enables more accurate detection as the variation in the biometric position is minimized.

[0129] In an exemplary embodiment, the microfluidic cartridge drive unit 30 includes an orbital system that includes at least one tray track that guides the tray and ensures that the biometric is placed directly below the light source 51 and the camera 62. The orbital system is configured to accommodate at least two edges of the tray and is capable of expanding in the length direction while holding the tray and the microfluidic cartridge 22 above the mounting structure to which the orbital system is configured to be fixed.

[0130] 1.1.2 Microfluidic Cartridge Operation Unit

[0131] The microfluidic cartridge drive unit 30 includes a microfluidic cartridge operation unit 41 that controls the fluid movement of the microfluidic cartridge 22 (see Figure 2 ). The microfluidic cartridge operation unit 41 includes an electrical connector 44 that serves as an interface for the microfluidic cartridge 22 to drive / control the power / current and supply it to the microfluidic cartridge 22 to drive the reagents and samples from the microfluidic chip 24 to the diagnostic chip 26 in a predetermined sequence for reaction.

[0132] Figure 4 A fluid control assembly 45 on the microfluidic cartridge operation unit 41 is shown. More specifically, the figure shows a cross-sectional view of two reservoirs on the microfluidic cartridge operation unit. In some exemplary embodiments, the microfluidic cartridge operation unit 41 further includes at least one fluid control assembly 45 that is configured to control the movement of at least one fluid within the microfluidic cartridge. The fluid control assembly 45 is positioned adjacent to the cartridge chamber. In an exemplary embodiment, the fluid control assembly 45 is located at a position less than 10 cm from the cartridge chamber. The fluid control assembly 45 changes the viscosity of at least one specific portion of the microfluidic cartridge by controlling the irradiation light and opening a valve that facilitates fluid movement, and the irradiation light provides heat on a specific portion of the microfluidic chip. The gas generated by the electrolysis of the hydrogel helps to push the reagent through the opening. In an exemplary embodiment, the specific portion is the plastic film that seals the microfluidic cartridge. The predetermined sequence is discussed in detail herein and is also shown in Figure 4 . Irradiating the plastic films covering different reservoirs in a specific order causes the reagents to leave the reservoirs and start reacting in a specific order, such as first the wash buffer, then the blocking buffer, then the antibody, and then the wash buffer again. Control signals and power are provided to the fluid control assembly 45.

[0133] 1.2 Optical Inspection Unit

[0134] As Figure 5The weight of the optical inspection unit 32 shown is less than a few kilograms (kg) and can be used for on-site analyte analysis / detection. The optical inspection unit 32 includes an optical sensor 48 and an illumination system 50. In some embodiments, the optical inspection unit 32 further includes one or more filters 56. In some embodiments, the optical inspection unit 32 further includes a reader 58 and a switch 60. The tray of the microfluidic cartridge drive unit 30 is below the optical inspection unit 32. The microfluidic cartridge drive unit 30 is configured such that when the microfluidic cartridge is assembled or fixed in the microfluidic cartridge drive unit 30, the diagnostic chip of the microfluidic cartridge is directly below the optical inspection unit 32 for inspection. The illumination system 50 includes at least one light source 51. In some embodiments, the illumination system 50 includes at least one light source 51 and / or at least one condenser lens 54. In an exemplary embodiment, the light source 51 can be a monochromatic or polychromatic laser or LED. The light source 51 should be strong enough to excite the fluorophore. In an exemplary embodiment, the light source 51 can be a high-brightness LED spotlight with a blue LED color, such as the high-brightness LED spotlight HBF-00-08-1-B-5V of TMS lite. The specifications of the TMS lite high-brightness LED spotlight HBF-00-08-1-B-5V are shown in Tables 1 and 2 below.

[0135] Table 1.

[0136] Mechanical information Housing material Aluminum Storage temperature range Temperature 0 - 45°C, humidity 20 - 85% Weight - Outer diameter 30 Inner diameter 6 Thickness 69

[0137] Table 2.

[0138]

[0139]

[0140] In another exemplary embodiment, the illumination system 50 includes a diode laser that radiates at least one laser beam having at least one predetermined wavelength onto the diagnostic chip 26 to generate at least one signal. The predetermined wavelength of the laser beam is selected such that at least one signal detectable by the optical sensor 48 can be generated. The user can select / control the intensity and wavelength of the laser beam through the control unit 28 to detect a specific analyte. The laser beam is steered at an angle onto the diagnostic chip 26 to avoid reflection and generate a higher-quality signal. The predetermined wavelength is, for example, in the range of 465 to 500 nm, 400 to 700 nm, 430 to 465 nm, 500 to 550 nm, 550 to 580 nm, 580 to 620 nm, or 620 to 700 nm.

[0141] In an exemplary embodiment, the light source 51 includes a light pipe 53 that emits light uniformly. The light pipe 53 is configured such that it guides the light to a condenser lens 54 or other optical components and helps to focus the light beam onto the biometric on the diagnostic chip. The light pipe 53 is aligned with the biometric on the diagnostic chip at a specific location on the microfluidic cartridge, and the position of the microfluidic cartridge is determined by the tray and the tray track.

[0142] In an exemplary embodiment, the illumination system 50 includes at least one condenser lens 54 such that the focusing of the light from the light source 51 is optimized. In some embodiments, the condenser lens 54 is located on the end of the light pipe 53 opposite the light source 51. In some embodiments, the condenser lens 54 is located in front of the light source 51. The focusing lens 54 and the camera 62 can each be independently mounted or fixed on one or more frames to prevent any unwanted movement during the optical setup. In an exemplary embodiment, the condenser lens 54 can be a convex lens with a focal length of 25.4 mm, such as the LB1761-N-BK7 double convex lens from Thorlabs Inc., in, f = 25.4 mm, uncoated. The specifications of the condenser lens 54 are shown as follows:

[0143] Design wavelength: 587.6 nm

[0144] Focal length: f = 25.3 ± 1%

[0145] Back focal length (REF): bf = 22.2 mm

[0146] Clear aperture: >90%

[0147] Surface quality: 40 - 20 scratch-dig

[0148] Centration: <3 arc minutes

[0149] Diameter tolerance: +0.0 / -0.1 mm

[0150] Thickness tolerance: ±0.1 mm

[0151] When the tray 52 is in its docking position, the microfluidic chamber is located below the optical sensor 48 and the illumination system 50. The optical sensor 48 includes a camera 62 and at least one objective lens 64. In some embodiments, the optical sensor 48 further includes at least one camera lens 55. The optical sensor 48 receives a signal from the diagnostic chip 26, which is generated by the illumination system 50 irradiating laser radiation onto the diagnostic chip 26 of the microfluidic cartridge 22 held on the tray of the cartridge chamber. Then, the received signal is sent to the control unit 28 for analysis. The optical sensor 48 can have a high quantum efficiency within its detection wavelength range. In one exemplary embodiment, the camera 62 of the optical sensor 48 can be a charge-coupled device (CCD) or any other suitable camera. In one exemplary embodiment, the camera 62 is a near-infrared optimized camera with a 2 / 3 type (diagonal 11.0 mm) CCD sensor.

[0152] The camera lens 55 of the optical sensor 48 can be any suitable camera lens or a higher quality lens, such as a microscope-grade lens, depending on the type of immunoassay used. In one exemplary embodiment, since the biometric is physically small, the camera lens 55 is responsible for assisting the camera in focusing on the biometric. In one exemplary embodiment, the camera lens 55 is a C-mount lens. In some embodiments, the C-mount lens is located between the camera and the objective lens. In some exemplary embodiments, the C-mount lens is firmly attached to the camera. In one exemplary embodiment, the focal length of the C-mount lens is 16 mm. In one exemplary embodiment, the objective lens 64 of the optical sensor 48 is a plano-achromatic objective lens, 4x magnification, 0.1 numerical aperture, and a working distance of 18.5 mm, such as the RMS4X-4X Olympus plano-achromatic objective lens, 0.10NA, 18.5mm WD from Thorlabs, Inc.

[0153] In an exemplary embodiment, the optical inspection unit 32 further includes one or more filters 56. The one or more filters 56 can be used to filter out any light with an undesired wavelength generated from the light source and any undesired noise in the signal picked up by the camera. Depending on the light source and fluorophore used, one or more filters 56 can be used. The illumination system 50 is connected to the filter. In an exemplary embodiment, the one or more filters 56 are mounted and aligned between the camera lens 55 and the objective lens 64. This allows any light with an undesired wavelength to be filtered out and only allows light with a specific wavelength or wavelength range to pass through and reach the biometric. The camera 62 is connected to the camera lens 55, and these two components are connected to the one or more filters 56. This connection to the one or more filters 56 allows any undesired signals (e.g., noise, which typically has a different wavelength and is generated by the biometric or any undesired reaction) to be filtered, and thus minimizes the undesired interference to the true signal. The one or more filters 56 are connected to the light pipe, which helps to focus the filtered light beam onto the biometric. In an exemplary embodiment, a fluorescence filter set for FITC fluorescein (emission wavelength of 513 - 556 nm and excitation wavelength of 467 - 498 nm) is used. For example, the 67 - 004 fluorescence filter set for FITC fluorescein from Techspec. The specifications of the 67 - 004 fluorescence filter set for FITC fluorescein are shown below:

[0154] Compatible fluorophore: FITC

[0155] Coating: Hard coating

[0156] Dichroic cut-off wavelength (nm): 506.00

[0157] Dichroic filter: #67-080

[0158] Emission filter: #67-031

[0159] Emission wavelength (nm): 513 - 556

[0160] Excitation filter: #67-028

[0161] Excitation wavelength (nm): 467 - 498

[0162] Manufacturer: EO

[0163] Substrate: Fused silica

[0164] Type: Fluorescence filter kit

[0165] Wavelength range (nm): 467 - 556

[0166] RoHS: Compliant

[0167] In some exemplary embodiments, the optical inspection unit 32 further includes a switch 60. In another exemplary embodiment, the switch 60 is a microswitch. The microswitch is attached to the back of the tray track and electrically connected to the power supply unit 65. When the tray 52 is pushed into the docking position through the tray track, the microswitch is automatically activated. After activation, the microswitch can turn on the reader to read the identification of the microfluidic cartridge.

[0168] In some exemplary embodiments, the optical inspection unit 32 further includes a reader 58 to read the identification of the microfluidic cartridge. In one exemplary embodiment, the reader 58 is a barcode reader. The barcode reader can read the 2D barcode attached to or fixed on the microfluidic cartridge.

[0169] In one exemplary embodiment, the user manually selects a suitable program to run the diagnostic chip or the microfluidic cartridge. In some embodiments, the program uses a specific predetermined sequence of electrical pulses to drive the appropriate reactions, analyze and use an appropriately sized microarray to calculate the results.

[0170] In some exemplary embodiments, an internal barcode reader is incorporated into the system, where the barcode reader is located above the position where the microfluidic cartridge will be placed. In one exemplary embodiment, the barcode is attached or fixed to the microfluidic cartridge ( Figure 5 ). In another exemplary embodiment, a two-dimensional (2D) code is attached or fixed to the microfluidic cartridge. The 2D code incorporating the identification of the microfluidic cartridge, the analyte or disease to be tested, and the expiration date of the chip is placed on the microfluidic cartridge during the manufacturing process. After the microfluidic cartridge is inserted into the tray, the barcode reader is activated, and the barcode reader automatically scans the 2D code. The software can automatically select the correct program to use based on the 2D code. This feature eliminates the need for manual selection of the pulse program, making the design more user-friendly and less prone to human error. In one exemplary embodiment, the software can also identify previously used or defective microfluidic cartridges. The software displays a warning message on the screen and does not continue to execute the program.

[0171] The components in the optical inspection unit 32 are arranged such that a compact integrated optical inspection unit is formed. This compact design results in a smaller and lighter diagnostic system. The diagnostic system should be small and light enough to be movable between clinics when needed. In one exemplary embodiment, the present invention is small and light enough to be carried onto domestic flights. In one exemplary embodiment, the dimensions of the device are approximately 30x30x30 cm 3 , and the weight is approximately 5 - 6 kg.

[0172] The following events associated with the optical inspection unit 32 are described:

[0173] S1. The user places the microfluidic cartridge into the tray or the microfluidic chamber.

[0174] S2. The user pushes the tray into the device guided by the tray rail.

[0175] S3. When the tray is pushed in, the switch is activated.

[0176] S4. The switch turns on the barcode reader.

[0177] S5. The reader reads the code printed on the microfluidic cartridge.

[0178] S6. The code contains the identification of the microfluidic cartridge, which prompts the software of the control unit to automatically select the program associated with this microfluidic cartridge.

[0179] S7. Once the software selects the correct program, a specific sequence of electrical pulses is generated, and the sequence of electrical pulses passes through the microfluidic cartridge via the electrical connector located at the bottom of the tray. This sequence of electrical pulses drives the reagents in the microfluidic chip out of their reservoirs and pushes them into the reaction chamber in a predetermined order. The electrical pulses can also drive the fluid control assembly 45 to facilitate the fluid movement within the microfluidic cartridge.

[0180] S8. Once the reaction is completed in the reaction chamber, the illumination system is activated, and the biological assay is excited by the light beam.

[0181] S9. The optical sensor captures the optical image, and the image is analyzed by the software.

[0182] S10. The results are displayed on the screen for the user to view. No manual interpretation is required.

[0183] 1.3 Control Unit

[0184] The control unit 28 generally includes a microprocessor (CPU), a memory, and an input / output (I / O) interface. The control unit 28 controls the quantitative and qualitative analysis, interface connection, and storage of the signals obtained from the optical inspection unit 32, and controls and monitors all operations of the diagnostic device 20.

[0185] The control unit 28 further includes a non-transitory computer-readable medium for storing computer-readable code such that when the code is executed by the microprocessor, it instructs all parts of the diagnostic device 20 to perform and operate the steps as described above and herein. The non-transitory computer-readable medium may include any known type of data storage and / or transmission medium, including magnetic media, optical media, random access memory (RAM), read-only memory (ROM), data caches, data objects, etc. Additionally, the memory may reside in a single physical location (including one or more types of data storage), or may be distributed across multiple physical systems in various forms.

[0186] In one embodiment, the control unit 28 includes software modules that may be required for system operation. These modules include an operating system, application modules, an image processing module, a microfluidic cartridge driver software module for controlling the fluid flow in the microfluidic chip 24 as described above, and a user interface software module. The operating system manages computer hardware resources and provides general services for all computer software modules. The operating system may be Apple iOS, Android, Microsoft Windows, or Linux. The operating system also integrates various communication protocols, either wired or wireless, such as local area network (LAN), USB, Wi-fi, Bluetooth, etc. The application modules are a set of programs designed to perform operations on the device. It manages the device's data as well as job data, program data, client data, microfluidic cartridge data, pump settings, optical sensor settings, and data collected from the optical inspection unit 32. The image processing module collects data from the optical inspection unit 32. The image processing module selects the target area of the diagnostic chip 26 and controls the acquisition of images therefrom. The image processing module also corrects the brightness and contrast of the acquired images. When receiving these images from the image processing module, the control unit 28 measures and compares the images of the diagnostic chip 26 according to the settings of the optical sensor 48. Then, the image processing module counts and calculates according to the set limits and sends the analysis results to the user interface software module. The microfluidic cartridge driver software module is designed to instruct the microfluidic cartridge driver unit 30 to control the current and the time at which this current is transmitted to the microfluidic pump at the microfluidic chip 24. The higher the current and / or the longer the time for transmitting this current, the more fluid can then be pumped from the reservoir 80. The user interface software module is an interface that allows the user to interact with the device through graphical icons, visual indicators (e.g., symbols and commands). By allowing the user to easily obtain, understand, add, edit, and delete information without any special skills, the user interface software module makes the device very user-friendly for non-technical personnel. With the help of the interaction of graphics, sound, and the transmission of notifications and commands given by the user interface software module, it also allows the user to feel that they are closely connected to the optical inspection unit 32.

[0187] 1.4 Power Supply Unit

[0188] A power supply unit 65 is provided in the device. The power supply unit 65 includes at least one rechargeable battery pack, a battery charger port, a power switch, and a power management electronic circuit. Conventional rechargeable battery packs can be made of lithium-ion, lithium polymer, or other high-capacity batteries. The rechargeable battery pack in the power supply unit 65 can support the operation of the device for several hours without a public power supply (e.g., in remote areas). The power supply unit 65 is equipped with a battery protection circuit system that can protect the rechargeable battery pack from overcharging, overcurrent, and over-temperature, thus ensuring the safety of the device and the user. The power supply unit 65 is also equipped with a battery connector to allow the user to replace a fully discharged battery with a fully charged spare battery during long-term use. The power management electronic circuit is used to convert the voltage of the rechargeable battery pack into different voltages required by different system units. The power management electronic circuit is connected to the control unit 28, the rechargeable battery pack, the microfluidic cartridge drive unit 30, and the optical inspection module. Whenever needed, the power management electronic circuit can start, terminate, and change the voltage to save the power consumption of the device. These command signals are given by the control unit 28. In addition, the battery charger provides direct current (DC) via the battery charger port at the back panel of the device to charge the rechargeable battery pack in the system. Even if the rechargeable battery pack runs out of power, the device can operate when a public or external power supply is provided. After the rechargeable battery pack is charged, the battery charger port can be removed. In an exemplary embodiment, the diagnostic platform can operate using a plug-in power supply or only rely on the battery. The use of rechargeable batteries enables the device to be taken outdoors and used in rural areas where power supply may be lacking.

[0189] In an exemplary embodiment, the specifications of the battery are shown as follows:

[0190] Type: RRC2024

[0191] Voltage: 14.40V

[0192] Capacity: 6.60Ah

[0193] Maximum charging current: 4.62A

[0194] Maximum charging voltage: 16.80V

[0195] Maximum discharge current: 10.00A

[0196] Dimensions: (L x W x H) 167.7mm x 107.6mm x 21.8mm (maximum)

[0197] Weight: 590g

[0198] In an exemplary embodiment, the battery can be carried on a domestic flight and shipped internationally when installed on a diagnostic platform.

[0199] In an exemplary embodiment, a fully charged battery supports device operation for at least about 5 hours.

[0200] In an exemplary embodiment, the battery is rechargeable and replaceable by the user. The battery enables the device to operate in areas without power or temperature control.

[0201] Example 2

[0202] 2. Microfluidic Cartridge

[0203] As Figure 6A 、 Figure 6B and Figure 6C shown, the microfluidic cartridge 22 includes a diagnostic chip 26 fixed to a microfluidic chip 24. In the illustrated embodiment, it is smaller than a credit card in size and has a thickness of 1 - 10 mm. The microfluidic chip 24 includes an electrical connection interface 78 for receiving control signals and power supplied through an electrical connector 44 in the cartridge chamber 42, a top portion 68, and a bottom portion 70 attached to the top portion 68. In this example, the top portion 68 and the bottom portion 70 are assembled together by an adhesive material or through a welding process. The bottom portion 70 can be made of an electrically insulating material (e.g., plastic and resin materials). As Figure 6A shown, the top portion 68 has a plurality of microgrooves 66, a channel opening fluidly connected to the microfluidic chip 24, and an adhesive 74 for attaching the microfluidic chip 24 at the channel opening. As Figure 6C shown, the bottom portion 70 of the microfluidic cartridge has a groove in which a microporous membrane 76 is to be placed. In an exemplary embodiment, the top portion 68 includes a plastic film that seals the microfluidic cartridge. The plastic film receives a light control signal provided by a fluid control component 45 of the microfluidic cartridge driver unit. When a sufficient light control signal is received at a specific valve position on the microfluidic chip 24, the plastic film covering the valve changes its viscosity. The change in viscosity causes the shape of the valve to change from a planar shape to a dome shape, thereby allowing the valve to open. Light control signals can be emitted at different times at different valve positions to control the order of reagent release (see Figure 4 ).

[0204] Now refer to Figure 6A and Figure 6C, the top portion 68 can be made of acrylic, polycarbonate, or a similar type of plastic. It can be transparent to allow the user to observe the fluid state inside the microfluidic chip 24. The plastic portion can be manufactured by a plastic injection molding process associated with other processes (e.g., hot embossing and micromachining methods). The top portion 68 contains a plurality of microgrooves 66 in a corresponding plurality of reservoirs 80, where at least one reservoir is configured to receive a sample from the top, and at least one reservoir is configured to hold at least one reagent to facilitate the reaction or interaction between the analyte interacting molecules and the analyte. Thus, the detection of the analyte can be promoted. The reagent held in at least one reservoir is selected from the group consisting of: wash buffer and blocking buffer. In one embodiment, the wash buffer is phosphate buffered saline (PBS), and the blocking buffer is PBS and bovine serum albumin (BSA). The sample is driven from the microfluidic chip 24 to the diagnostic chip 26 for analyte reaction / interaction on the diagnostic chip 26. In each reservoir 80, at least one microfluidic channel 86 is located below the microgroove 66, at the interface between the top portion 68 and the bottom portion 70, as Figure 6A and Figure 6C shown. The reagent and the sample are driven from the microfluidic chip 24 to the diagnostic chip 26 through the microfluidic channel 86 and then to the channel opening.

[0205] Each reservoir 80 is integrated with a micropump constructed with a small amount of hydrogel 82 placed therein (see Figure 6C ). The hydrogel 82 contacts the conductive circuit traces 84 bonded to the construction material of the bottom portion 70. These micropumps are operated by an electric current supplied through the conductive circuit traces 84. These micropumps push the sample and the reagent through the microfluidic channel 86 by expanding and contracting the hydrogel 82, thereby transporting the sample and the reagent to the channel opening. The expansion and contraction of the hydrogel 82 are controlled by the microfluidic cartridge operation unit 41 of the microfluidic cartridge driver unit 30 of the diagnostic device 20 by sending signals and power through the connection between the electrical connector 44 and the electrical connection interface, which is also electrically connected to the conductive circuit traces 84. These pumps are encapsulated so that this can avoid contamination and cross - contamination problems. In an exemplary embodiment, the volume of each reservoir 80 is in the range of 20 - 150 μl. In an exemplary embodiment, the number of reservoirs in a microfluidic cartridge is 5 - 12. For clarity, "mixed sample and reagent" is synonymous with "mixture of sample and reagent" and refers to the mixture of sample and reagent formed by the above steps.

[0206] In an exemplary embodiment, a removable lid is provided at the opening for sample introduction to prevent leakage or evaporation of the sample (see Figure 6B ).

[0207] In an exemplary embodiment, the expansion and contraction of the hydrogel 82 is further controlled by a fluid control assembly 45 that receives signals from a control unit and electrical power from a power source (see Figure 4 ). After receiving the signal, the fluid control assembly 45 irradiates light onto a specific area of the plastic film on the microfluidic chip. The irradiated light can change the viscosity of the hydrogel, thereby facilitating the pushing of samples and reagents through the microfluidic channels by the micropump.

[0208] Each electrical connector 44 on the bottom of the microfluidic cartridge 22 is associated with a specific reservoir. When connected, an electrical pulse passes through the electrical connector 44 and electrolyzes the hydrogel in the specific reservoir. The electrolysis process generates oxygen and hydrogen, and these gases expand to push the fluid inside the reservoir out of the reservoir. The valve at the reservoir outlet is sealed by a plastic film, but when irradiated, the valve opens and allows the reagent in the reservoir to be pushed into the channel / next reservoir (depending on the location of the outlet connection). The flow rate of the reagent is controlled by an electrical pulse sequence that is transmitted to the electrical connector 44 at the bottom of the chip.

[0209] The diagnostic chip 26 can be made of glass, silicon, or plastic and is fixed to the microfluidic chip 24. The bottom surface of the diagnostic chip 26 (i.e., the surface facing the channel opening) pre-coated with an array of detection points is arranged facing the channel opening and is in fluid communication with the channel opening. The detection point array can react / interact with the analyte present in the sample to generate at least one signal under certain conditions (e.g., generating one or more fluorescent signals when irradiated with laser radiation of a certain wavelength). In one embodiment, each of these detection points contains at least one analyte-interacting molecule that reacts / interacts with at least one analyte. In a particular embodiment, the analyte-interacting molecule is a specific protein or peptide that binds to at least one specific virus / bacterium (e.g., antigen) in its intact state or in a partially suitable form for detection. The detection point array is located within 1 - 15 millimeters (mm) around the channel opening such that when the mixed sample and reagent are pumped out of the channel opening, they can be dispersed through the array. The bottom surface of the diagnostic chip 26 facing the microfluidic chip 24 is first coated with a first coating that is used to fix the subsequently coated detection points without changing the configuration of the detection points (e.g., maintaining the binding sites of the analyte-interacting molecules contained in the detection points to be accessible to one or more analytes). The first coating should also create a hydrophilic environment for the analyte to react / interact. It is optimized to minimize non-specific reactions / interactions, thereby reducing the background noise signal in this device. Once the first coating is completed, the detection points are deposited on the bottom surface of the diagnostic chip 26 in a predetermined pattern (e.g., an array). The drop-on-demand method is selected to disperse them onto the diagnostic chip 26. In one embodiment, the drop-on-demand method can be performed by a microarray printer. The diagnostic chip 26 with the mixed reagent and sample (which may contain an analyte) reacting / interacting thereon can be detached from the microfluidic chip 24 and placed on the diagnostic chip holder 58 for further analysis by the optical inspection unit 32. The mixed sample and reagent on the diagnostic chip 26 can be dried before or after detaching the diagnostic chip 26 from the microfluidic chip 24.

[0210] In an exemplary embodiment, the microfluidic cartridge 22 (test cartridge) consists of (1) the bioassay printed on the diagnostic chip 26 and (2) the microfluidic chip 24 pre-loaded with the reagents required for the proper operation of the microfluidic cartridge 22. The production sequence of the microfluidic cartridge 22 is shown in Figure 7 First, the bioassay is fixed on the diagnostic chip 26. Second, the diagnostic chip 26 is attached or fixed to the microfluidic chip 24 to form the microfluidic cartridge 22. Then, one or more reagents are pre-loaded into one or more reservoirs of the microfluidic cartridge 22. Finally, the reagent chamber is sealed with, for example, a plastic film.

[0211] In an exemplary embodiment, the biometric can be based on an immunoassay or any other type of biosensing system. The biometric consists of one or more positive controls and negative controls. Each biometric can detect one disease at a time or can detect multiple diseases simultaneously. Unlike most near-patient tests, no external positive or negative control runs are required before running the microfluidic cartridge 22.

[0212] In an exemplary embodiment, the diagnostic chip 26 and the microfluidic chip 24 are pre-fixed during the manufacturing process and do not separate during the reaction and detection steps. The diagnostic chip 26 is pre-attached to the microfluidic chip 24. This exemplary embodiment eliminates errors or any other inaccuracies caused when the user attaches the diagnostic chip 26 to the microfluidic chip 24. This exemplary embodiment eliminates the disassembly step, thereby eliminating or at least significantly reducing the risk of (1) reagent leakage (resulting in contamination) or (2) the diagnostic chip getting stuck and cutting the user.

[0213] In an exemplary embodiment, all reagents are pre-loaded into the microfluidic chip 24 and sealed during the manufacturing process. Given that near-patient tests are typically performed by trained non-professionals, pre-loading the reagents eliminates the possibility of human error (e.g., loading reagents into the wrong slots, improper use of pipettes, adding the wrong volume of reagents, and spilling reagents during the loading process). Pre-loading the reagents can also minimize user contact with chemicals. The user-friendly microfluidic cartridge eliminates all preparation processes related to reagent loading, thus minimizing the possibility of human error and shortening the preparation time by five minutes.

[0214] In an exemplary embodiment, the shape of the microfluidic cartridge is configured such that there is only one possible way to assemble or insert the microfluidic cartridge 22 (and thus, the diagnostic chip 26) into the microfluidic chamber 42 of the tray 52. The microfluidic cartridge 22 is fixed in the desired position and orientation.

[0215] In an exemplary embodiment, the coating process and deposition steps of the detection points (containing, for example, the antigen of the H7N9 influenza virus) on the surface of the diagnostic chip 26 are shown in Figure 8 and are detailed below:

[0216] For the cleaning step 88: Partially immerse the diagnostic chip 26 made of glass material into a 250 milliliter (ml) beaker containing acetone. Then, perform ultrasonic treatment for 5 minutes (min) to clean the immersed portion of the diagnostic chip 26. Then, transfer the diagnostic chip 26 to another 250 ml beaker containing ethanol using tweezers. Then, perform ultrasonic treatment again for 5 minutes.

[0217] For hydroxylation step 90: Transfer seventy-five (75) ml of 95% sulfuric acid into a 250 ml beaker. Then, pipette twenty-five (25) ml of 34.5% volume by volume (v / v) hydrogen peroxide into the same beaker such that the final concentration of hydrogen peroxide is 8.63% and the resulting volume ratio of concentrated sulfuric acid and 34.5% hydrogen peroxide (piranha solution) is 1:3 v / v. Thus, then partially immerse the diagnostic chip 26 from the cleaning step 88 into the above solution at room temperature for 2 hours (hr). Then, pick up the treated diagnostic chip 26 from the piranha solution using forceps and rinse it with ultrapure water using a wash bottle for 5 minutes. Discard the piranha solution into a waste bottle. Next, transfer the treated diagnostic chip 26 using forceps into a 250 ml beaker containing 95% absolute ethanol. Then, perform sonication for 5 minutes. Then, repeat this step for the treated diagnostic chip 26 once again in another 250 ml beaker containing purified water.

[0218] For acidification step 92: Transfer twenty-five (25) ml of hydrochloric acid into a 50 ml reaction tube. Then, add twenty-five (25) ml of ethanol into the same tube. Then, transfer the diagnostic chip 26 from the hydroxylation step 90 into the above solution using forceps and react at 37 degrees Celsius (°C) for 3 hours. Then, pick up the treated diagnostic chip 26 from the solution using forceps and rinse it with ultrapure water using a wash bottle for 5 minutes. Discard the solution into a waste bottle. Thus, then transfer the washed diagnostic chip 26 using forceps into a 250 ml beaker containing 95% absolute ethanol. Then, perform sonication for 5 minutes.

[0219] Then, transfer the diagnostic chip 26 using forceps into another 250 ml beaker containing purified water. Then, perform sonication again for 5 minutes. After that, then transfer the treated diagnostic chip 26 using forceps into a 250 ml beaker and incubate in an oven to dry at 60 °C for 30 minutes, followed by the amination step 94 described below.

[0220] For amination step 94: Pipette 6.641 grams (g) of (3-aminopropyl)triethoxysilane (APTES) (sensitive to moisture) into a 50 ml reaction tube (used for the first time) at room temperature. Then, pipette 43 ml of ethanol into the same tube. Next, add 0.1 ml of acetic acid to the same tube. Then, transfer the treated diagnostic chip 26 from the acidification step 92 into the above solution and react at 50 °C for 24 hours. Thus, then transfer the diagnostic chip 26 with tweezers into a 250 ml beaker containing 95% absolute ethanol. Then, perform ultrasonic treatment for 5 minutes. Then, transfer the diagnostic chip 26 with tweezers into another 250 ml beaker containing purified water and perform ultrasonic treatment again for 5 minutes. After that, transfer the treated diagnostic chip 26 with tweezers into a 250 ml beaker and incubate in an oven to dry at 120 °C for 30 minutes.

[0221] For addition step 96 - adding aldehyde groups: Prepare 25% glutaraldehyde in a 50 ml reaction tube respectively. Then, transfer the treated diagnostic chip 26 from the amination step 94 into the above solution and react at room temperature for 24 hours. As a result, then transfer the diagnostic chip 26 with tweezers into a 250 ml beaker containing 95% absolute ethanol. Then, perform ultrasonic treatment for 5 minutes. Then, transfer the diagnostic chip 26 with tweezers into another 250 ml beaker containing purified water and perform ultrasonic treatment again for 5 minutes. Then, repeat this step once again in another 250 ml beaker containing purified water. Next, transfer the treated diagnostic chip 26 with tweezers into a 250 ml beaker and incubate in an oven to dry at 60 °C for 30 minutes.

[0222] In an alternative embodiment, the diagnostic chip 26 is rinsed with deionized water and then ultrasonically treated for 5 minutes in a 1:3 volume ratio (v / v) cleaning detergent:deionized water mixture. Subsequently, the cleaned diagnostic chip 26 is immersed in deionized water for 5 minutes (after decantation) and finally immersed in acetone for 5 minutes. Then, the cleaned diagnostic chip 26 is dried with compressed air. Next, 3-glycidoxypropyltrimethoxysilane is dissolved in acetone and pipetted to mix it with a collodion solution (10%, purchased from Wako). The diagnostic chip 26 is dipped into this mixture and slowly taken out from the mixture. Then, the diagnostic chip 26 is dried in air and turns into a white film. The coated diagnostic chip 26 is further incubated at 80 °C for 1 hour. Then, after equilibration at room temperature, the diagnostic chip 26 is immersed in 20 ml of ethanol for 5 minutes. Then, the diagnostic chip 26 is thoroughly rinsed with water, subsequently rinsed with acetone and water again. The diagnostic chip 26 becomes transparent and can be stored at room temperature before use (e.g., the printing step 98 described below).

[0223] For printing in step 98: printing of PBS buffer, H7N9 antigen, or BSA on the diagnostic chip 26 coated with the aldehyde groups described in step 96 or on the transparent diagnostic chip 26 obtained from the acidification step 92: For printing with PBS buffer, prepare an ink formulation of a 4 ml PBS solution of 40% glycerol and fill it into the printer cartridge. For printing H7N9 antigen, prepare an ink formulation of a 1.5 ml PBS solution of 0.1 ml H7N9 antigen (purchased from SinoBiological, 1 milligram (mg) / ml) and 40% glycerol, and fill the mixture into the printer cartridge. For printing with BSA, prepare an ink formulation with a 1 ml solution of 1000 micrograms (μg) / ml BSA (purchased from Thermo, product number 23208) and a 4 ml PBS solution of 40% glycerol, and fill the mixture into the printer cartridge. Next, set up the FUJTFILM Dimatrix material printer (model DMP-2831). Then, fix the prepared cartridge onto the print head (Note: Ensure that no bubbles are observed in the solution, especially those trapped in the inlet flow channels. Otherwise, gently press the cartridge with your finger until the bubbles are removed from the channels). Then, verify the droplet stability of the solution from the 16 nozzles. Also select at least one nozzle with good conditions and dot-print it onto the processed diagnostic chip 26 from the addition step 96. Then, dot-print 200 μm of H7N9 antigen or BSA onto the processed diagnostic chip 26. Then, transfer the printed diagnostic chip 26 to a covered petri dish and incubate it in a drying oven at 37 °C for 2 hours in the drying step 100.

[0224] Then, attach the printed surface of the processed diagnostic chip 26 made of glass material from the drying step 100 to the top portion 68 of the microfluidic chip 24 loaded with the test sample as described above using the adhesive 74, and after reacting / interacting with the sample containing the analyte, the microfluidic cartridge 22 will be optically inspected by the optical inspection unit 32.

[0225] Example 3

[0226] Testing method

[0227] Another exemplary embodiment provides for the operation of a point-of-care diagnostic method and diagnostic system. Reagents for facilitating analyte detection are pre-loaded into separate reservoirs 80 and sealed during the manufacturing process. The reagents held in at least one reservoir are selected from the group consisting of: wash buffer (e.g., PBS), blocking buffer (e.g., bovine serum albumin (BSA)), lysis buffer (e.g., PBS), antigen, antibody, and fluorophore (e.g., PBS solution of fluorescein). In one embodiment, the wash buffer is PBS and the blocking buffer is PBS and BSA. In one exemplary embodiment, the microfluidic cartridge contains 5-12 reservoirs for holding reagents or samples. In some embodiments, the reagent volume is between 20-200 ul. In some embodiments, the reagent volume is 50 uL. The reagents can be held in one or more reservoirs. For example, if the capacity of one reservoir is not sufficient to hold all of the required volume of a particular reagent, additional reservoirs can be used for the same reagent.

[0228] During the manufacturing process, the diagnostic chip 26 is pre-fixed to the microfluidic chip 24. By dispensing a sample into the reservoir 80 during the loading step, the microfluidic chip 24 is first loaded with an appropriate amount of sample (e.g., a serum sample, a nasal swab, or a nasopharyngeal swab), which may contain the analyte. In an exemplary embodiment, the sample volume is between 20 - 200 ul. The surface of the diagnostic chip 26 with the detection point array and the first coating faces the channel opening and the microfluidic chip 24. The detection point array and the first coating will be located within 1 - 15 mm from the channel opening. Then, in the docking step, the microfluidic cartridge 22 is docked to the cartridge chamber 42 of the microfluidic cartridge drive unit 30 by pushing the electrical connection interface through the microfluidic cartridge receiving hole, such that the electrical connection interface will contact the electrical connector 44. In an exemplary embodiment, the microfluidic chip of the microfluidic cartridge will be directly beneath the fluid control assembly 45. Then, when receiving a signal from the switch, the identifier of the microfluidic cartridge is read by the reader, wherein the signal is sent when the tray is inserted into the docking position along the tray track. In an exemplary embodiment, the microfluidic cartridge is identified by a 2D code and read by a barcode reader. The microfluidic cartridge is identified by the control unit and the required predetermined sequence is automatically selected. In the step of dispensing the analyte, the mixed sample and reagent are dispensed across the detection point array. This is accomplished by flowing the sample and reagent from the reservoir 80 through the microfluidic channels 86 of the microfluidic chip 24 to the channel opening. When receiving current and signals from the microfluidic cartridge chamber via the electrical connector 44 through the electrical connection interface, the micropump drives the sample through the microfluidic channels 86 according to the time, speed, and sequence indicated by the microprocessor of the control unit 28. The mixed sample and reagent exiting the channel opening (the sample is mixed with the reagent when flowing through the microfluidic channels 86 of the microfluidic chip 24 as described above) are dispensed across the bottom surface of the diagnostic chip 26. Any air bubbles in the reservoir 80 will be removed through the microporous membrane 76 located at the bottom portion 70 of the microfluidic chip 24 when the sample passes through it. The area where the mixed sample and reagent are dispensed covers the location where the detection point array is located, such that the analyte can react / interact with the analyte interaction molecules in the detection points. In one embodiment, the step of dispensing the analyte may further include the step of further driving the microfluidic chip 24 through the microfluidic channels 86 of the microfluidic chip 24 to the diagnostic chip 26 to dispense a second auxiliary reagent located at one reservoir 80, thereby attaching a second molecule to facilitate the detection of the analyte in the reaction or interaction after the mixed sample and reagent are dispensed on the detection point array. When the pumping and analyte reaction / interaction stop, the microfluidic cartridge 22 remains in the same position in the cartridge chamber 42 of the microfluidic cartridge drive unit 30.In an exemplary embodiment, the step of dispensing the analyte may further comprise the steps of: driving the fluid control assembly 45 to change the viscosity of at least one specific portion of the microfluidic cartridge by controlling the irradiated light on a specific portion of the microfluidic chip and opening the valves that facilitate fluid movement. The mixed sample and reagent on the diagnostic chip 26 may be dried. Thereafter, the analysis step may be initiated. The diagnostic chip 26 of the microfluidic cartridge is located below the optical sensor 48 and is not separated from the microfluidic cartridge after the step of dispensing the analyte. After receiving a start signal from the microprocessor, a light beam (e.g., a laser beam) from the illumination system 50 is then directed onto the diagnostic chip 26 to generate at least one signal (if the mixed sample and reagent contain an analyte) that can be detected by the optical sensor 48. In one embodiment, the at least one signal comprises a fluorescence signal that is generated when the diagnostic chip 26 is irradiated with light of an appropriate wavelength (e.g., 488 nm). The collected signal will be converted into digital data, which will then be transferred to and analyzed in the microprocessor of the control unit 28 to quantitatively or qualitatively determine the presence of the analyte. The results will be displayed on the display unit 34 of the device in a relatively short time (rapidly) (e.g., in the range of 10 - 25 minutes).

[0229] In an exemplary embodiment, there are a number of steps that require manual assembly and disassembly of the microfluidic cartridge, as well as manual selection of the test program.

[0230] In an exemplary embodiment, the present invention has been designed to have minimal human involvement, which minimizes the likelihood of human error. After all the reagents are pre-loaded into the microfluidic cartridge and sealed, only the sample chamber inlet is exposed and is the only obvious inlet where the sample should be loaded. This design minimizes the likelihood that the user will load the sample into the wrong chamber. When the microfluidic cartridge is inserted into the device, the barcode reader scans the data matrix on the microfluidic cartridge and either rejects the cartridge (if it has already been used) or accepts the microfluidic cartridge and automatically selects the correct test program. This feature prevents any used microfluidic cartridge from being accidentally reused and prevents the user from making mistakes when selecting the test program on the diagnostic platform. The software embedded in the diagnostic platform analyzes the test results and displays them on the screen, which eliminates any possibility of human misinterpretation when reading the results. Figure 9 Exemplary report details for displaying the test results on the screen are shown. The report details show a direct result interpretation, i.e., both the positive control and the negative control are valid, and the target influenza A is detected.

[0231] Accordingly, exemplary embodiments of the present invention have been fully described. Although the description refers to specific embodiments, it will be apparent to those skilled in the art that the present invention can be practiced by changing these specific details. Therefore, the present invention should not be construed as limited to the embodiments set forth herein.

[0232] For example, the device may further include at least one USB port or any other data communication device to allow operation of a general data transfer communication protocol. A display unit is provided in the device for a human-machine interface. The display unit 34 is a high-resolution color display, which may be a liquid crystal display (LCD), an organic light-emitting diode (OLED), or other types of displays. The display unit may be combined with a touch screen panel; thus, it can receive commands from a human finger touch. The display unit is connected to the control unit 28. However, the way it displays the displayed content is through a graphical user interface.

[0233] Exemplary microfluidic chips that can be used may be the microfluidic chips disclosed in German Patent Application Nos. DE102010061910.8, DE102010061909.4, and DE502007004366.4.

[0234] In yet another alternative embodiment, instead of using at least one laser beam, at least one light beam may be used to generate at least one signal for analysis. In this alternative embodiment, the illumination system 50 emits at least one light beam having at least one predetermined wavelength onto the diagnostic chip 26. The illumination system 50 includes a light-emitting diode (LED), at least one filter, and at least one dichroic mirror.

[0235] In another embodiment, the illumination system 50 may have more than one diode laser or more than one LED.

[0236] In yet another embodiment, the camera 62 of the inspection unit 32 may be a digital high-resolution camera 62, where the sensor is selected from the group consisting of: complementary metal oxide semiconductor (CMOS) sensors and charge-coupled device (CCD) sensors. The megapixel count of the image sensor of the digital high-resolution camera 62 is in the range of 1.0 megapixel to 30 megapixels.

[0237] In yet another embodiment, the diagnostic device 20 may include a plurality of microfluidic cartridge drive units 30 and a plurality of optical inspection units 32, such that multiple analyses / diagnoses can be run simultaneously. Although we have described multiple embodiments of the present invention, it should be understood that these examples can be changed to provide other embodiments of the present invention. Therefore, the scope of the present invention should be defined by the following claims rather than by the specific embodiments provided herein.

[0238] Numbered Embodiments

[0239] The present invention will be further described with reference to the following numbered embodiments.

[0240] 1. An apparatus for detecting at least one analyte from a sample, comprising:

[0241] A microfluidic cartridge drive unit, comprising:

[0242] A tray including a cartridge chamber configured to receive a microfluidic cartridge, the microfluidic cartridge being configured for a reaction, wherein the reaction includes interacting or reacting with the analyte; and

[0243] A microfluidic cartridge operation unit including at least one electrical connector configured to connect to and electrically connect with the microfluidic cartridge;

[0244] An optical inspection unit configured for analyte detection, wherein the analyte detection includes detecting at least one signal generated by the microfluidic cartridge due to the presence of the analyte under a predetermined condition, the optical inspection unit including:

[0245] A lighting system configured to transmit light to the microfluidic cartridge to provide the predetermined condition;

[0246] An optical sensor configured to detect the at least one signal;

[0247] At least one filter configured to filter out any unwanted wavelengths or noise from the light generated by the lighting system; and

[0248] A control unit configured to control the quantitative and qualitative analysis, interface connection, and storage of the at least one signal obtained from the optical inspection unit, and to control and monitor the operation of the apparatus;

[0249] wherein the tray is configured such that the reaction and the analyte detection are performed at the same location on the same microfluidic cartridge.

[0250] 2. The apparatus according to embodiment 1, wherein the tray is configured such that the tray is slidably removable to receive the microfluidic cartridge in a docking position.

[0251] 3. The apparatus according to embodiment 2, wherein the tray further includes an anchoring system to secure the microfluidic cartridge.

[0252] 4. The apparatus according to embodiment 3, wherein the anchoring system includes two anchoring clips positioned orthogonally to each other.

[0253] 5. The apparatus according to embodiment 3 or embodiment 4, wherein the anchoring system is configured such that the tolerance of the position of the microfluidic cartridge is less than 0.1 mm.

[0254] 6. The device according to any one of embodiments 1 to 5, wherein the optical inspection unit further comprises a reader to identify the identification of the microfluidic cartridge and a required predetermined sequence.

[0255] 7. The device according to embodiment 6, which further comprises a switch.

[0256] 8. The device according to any one of claims 1 to 7, wherein the optical inspection unit further comprises at least one lens for focusing an image.

[0257] 9. The device according to any one of embodiments 1 to 8, wherein the microfluidic cartridge operation unit further comprises at least one fluid control component configured to facilitate movement of at least one fluid within the microfluidic cartridge.

[0258] 10. The device according to any one of embodiments 1 to 9, wherein the optical sensor comprises a camera and at least one objective lens.

[0259] 11. The device according to claim 9, wherein the optical sensor is selected from the group consisting of: a complementary metal oxide semiconductor (CMOS) sensor and a charge coupled device (CCD) sensor.

[0260] 12. The device according to any one of embodiments 1 to 11, wherein the illumination system comprises at least one light source and optionally comprises at least one condenser lens.

[0261] 13. The device according to any one of embodiments 12, wherein the light source comprises at least one light tube.

[0262] 14. The device according to any one of embodiments 1 to 13, wherein the analyte is an influenza virus antigen and the wavelength of the diode laser is 488 nm.

[0263] 15. The device according to any one of embodiments 1 to 14, wherein the control unit is capable of controlling the microfluidic cartridge drive unit.

[0264] 16. The device according to any one of embodiments 1 to 15, wherein the device comprises a power supply, the power supply comprising a built-in rechargeable battery.

[0265] Example 4

[0266] For the following examples, the term "microfluidic section" refers to the "microfluidic chip" used in the previous example; the term "microvalve" refers to the "valve" used in the previous example; the term "diagnostic section" refers to the "diagnostic chip" used in the previous example; the term "track assembly" refers to the "track system" used in the previous example; the term "optical unit" refers to the "optical inspection unit" used in the previous example; the term "lighting assembly" refers to the "lighting system" used in the previous example; the term "sensor assembly" refers to the "optical sensor" used in the previous example; the term "cartridge drive unit" refers to the "fluid control assembly" used in the previous example; the term "tray lid" refers to the "tray plate" used in the previous example; the term "microchannel" refers to the "microfluidic channel" used in the previous example.

[0267] Now refer to Figure 10A , which shows a diagnostic system 101 that includes a portable diagnostic device 300 and a microfluidic cartridge 200 that operates with the portable diagnostic device 300. The microfluidic cartridge 200, which includes a microfluidic section 210 and a diagnostic section 220, is configured to collect and manipulate at least one sample that may contain at least one analyte. The microfluidic cartridge 200 also houses and / or holds at least one reagent. The portable diagnostic device 300 is a portable, hand-held, and compact device that includes a microfluidic cartridge drive unit 320, an optical unit 330, and an optional control unit 340. In this example, the optical unit 330 is an optical inspection unit. In some embodiments, the portable diagnostic device 300 optionally includes a user interface unit 350 for connection to a user interface. In this example, the user interface unit 350 is a display unit. The control unit 340 controls and is connected to the microfluidic cartridge drive unit 320, the optical unit 330, and the user interface unit 350. The microfluidic cartridge drive unit 320 is configured to house and drive the microfluidic cartridge 200 such that the collected sample and reagent are run through the microfluidic section 210 and the diagnostic section 220 in a predetermined order. After the reaction is completed in the predetermined order, the microfluidic cartridge drive unit 320 also allows for inspection or analysis of the diagnostic section 220 at the same location on the same microfluidic cartridge. The optical unit 330 is configured to inspect the diagnostic section 220 at the same location on the same microfluidic cartridge 200 where the reaction also takes place to analyze the presence of the analyte. The user interface unit 350 is configured to display relevant information containing the analysis / diagnosis results to the user.

[0268] Example 5

[0269] Now refer to Figure 10B, which shows another exemplary embodiment of the diagnostic system 101, the diagnostic system including (1) a portable diagnostic device 300 and (2) a microfluidic cartridge 200 that operates with the portable diagnostic device 300. In this example, the microfluidic cartridge 200 includes a microfluidic section 210 and a diagnostic section 220. The microfluidic section 210 further includes at least one microvalve 216 and at least one micropump 215. The portable diagnostic device 300 is a portable, handheld, and compact device that includes a control unit 340, a microfluidic cartridge drive unit 320, an optical unit 330, and a cartridge receiving unit 310. In this example, the portable diagnostic device 300 further includes an identification unit 370 to identify the identification of the microfluidic cartridge 200. Figure 10B Shows that the control unit 340, the microfluidic cartridge drive unit 320, the optical unit 330, the user interface unit 350, the cartridge receiving unit 310, and the power supply unit 360 (not shown) are encapsulated in a stand-alone diagnostic device. In this example, the control unit 340 is electrically connected to the cartridge receiving unit 310, the microfluidic cartridge drive unit 320, the optical unit 330, and the user interface unit 350 to ensure that the microfluidic cartridge 200 is in a desired designated area for analysis, control the fluid flow in the microfluidic cartridge 200, control the quantitative and qualitative analysis, interface connection, and storage of the at least one signal obtained from the optical inspection unit, and control and monitor the operation of the device. In some exemplary embodiments, the cartridge receiving unit 310 includes a tray 311 and a track assembly 312. In this example, the tray 311 is slidable from the cartridge receiving unit 310 and includes a cartridge chamber for accommodating the microfluidic cartridge 200, such that the user can pull out at least a portion of the tray 311 from the portable diagnostic device 300, mount the microfluidic cartridge 200 onto the cartridge chamber of the tray 311, and insert the tray 311 into the track assembly 312 to ensure that the microfluidic cartridge is positioned at a desired designated area of the portable diagnostic device 300. In another exemplary embodiment, the tray 311 is slidably removable from the cartridge receiving unit 310, such that the user can completely remove the tray 311 from the device. The track assembly 312 is fixedly attached to the portable diagnostic device 300 and is configured to accommodate the tray 311 into which the microfluidic cartridge 200 is inserted. In one exemplary embodiment, the portable diagnostic device 300 includes a microfluidic cartridge receiving cavity (not shown) on its front panel for accommodating the microfluidic cartridge 200. The portable diagnostic device 300 can also be encapsulated in a stand-alone housing.

[0270] Example 6

[0271] Microfluidic Cartridge

[0272] Now refer to Figure 11A, which shows an exemplary embodiment of a front view (left), side view (middle), and rear view (right) of the microfluidic cartridge 200. The microfluidic cartridge 200, which includes a microfluidic section 210 and a diagnostic section 220, is configured to collect and manipulate at least one sample that may contain at least one analyte. In this example, the diagnostic section 220 includes a diagnostic chip (not shown) and a tape 224. The microfluidic cartridge 200 may also include at least one reactant disposed on the diagnostic chip (not shown). In this example, the tape 224 fixedly attaches the diagnostic chip to the diagnostic section 220. The tape 224 has a certain thickness and is made of a plastic material (e.g., polycarbonate) that is coated with an adhesive material on both opposite sides. The tape 224 has an enclosed area therein, thereby forming a diagnostic chamber for pre-loaded reactants and a reaction chamber for fluid communication between the diagnostic section 220 and the microfluidic section 210. In this example, an inlet 226 for fluid (e.g., fluid and reagent from the microfluidic section) and a reservoir outlet 228 for waste are disposed within the enclosed area of the tape 224. In some embodiments, the at least one reactant is pre-supplied on the diagnostic chip 220, that is, the reactant is pre-loaded during the manufacturing process, thus saving the user's effort, resources, and time for preparing the diagnostic chip. The microfluidic cartridge may include a combination of microvalves, microchannels, reservoirs, inlets, and outlets, etc., which are positioned in various configurations to allow various geometries for fluid transfer. In some embodiments, the microfluidic cartridge may include at least one sample reservoir and at least one reagent reservoir. Additionally, the microfluidic cartridge may be made with a built-in waste reservoir to handle fluids, such as biohazardous materials, after analysis. In the illustrated embodiment, it is smaller than a credit card, has a thickness of 1 - 10 mm, and dimensions of approximately 30 - 60 mm x 50 - 80 mm. In another exemplary embodiment, the thickness of the microfluidic cartridge may be approximately 5 mm, and the dimensions may be approximately 40 mm x 60 mm. The inlet of the sample reservoir is covered by a sample lid 212, thereby allowing the user to open the sample lid 212 when applying a sample and keeping the sample reservoir closed to avoid potential contamination. The overlay (i.e., the microvalve membrane 240) has been removed to show the inlets and outlets 218a, 218b, 218c, 218d, 218e, and 218f. In this example, 219a, 219b, 219c, and 219d are the inlets for reagents respectively, which allows different reagents to be introduced into each corresponding reagent reservoir 213 (not shown) during the manufacturing process, thus saving the user's effort, resources, and time for applying the appropriate reagents. 218a, 218b, 218c, 218d, 218e, and 218f are inlet / outlet node pairs of the corresponding reagent reservoirs (not shown). The microfluidic cartridge 200 may also include an indicator that shows the cartridge identification 230 of the microfluidic cartridge 200. In an exemplary embodiment, the cartridge identification 230 may be fixedly attached to the top portion.In another exemplary embodiment, the cartridge identifier 230 may be fixedly attached to the microfluidic valve membrane 240. In this instance, the cartridge identifier 230 is shown as a unique serial number and a two-dimensional (2D) barcode, which can be identified by an identification unit 370 (not shown). The microfluidic cartridge 200 includes an electrical connection interface 2151 for receiving control signals and power provided through an electrical connector disposed on a cartridge chamber of a cartridge receiving unit (not shown).

[0273] Figure 11A (Right) shows the opposite side (bottom side) of the microfluidic cartridge 200. The microfluidic chip 210 includes an electrical connection interface 2151 for receiving control signals from a device to supply power or current to the microfluidic cartridge 200. Figure 11A It is also shown that the diagnostic portion 220 is at least partially transparent for sample detection. The microfluidic cartridge 200 also includes a cavity 291 of a microporous membrane.

[0274] Now refer to Figure 11B, the microfluidic valve membrane 240, the sample cover 212, the diagnostic chip 222, and the tape 224 are blown out from the microfluidic cartridge 200 for better illustration. In this example, the microfluidic valve membrane 240 is a membrane having microfluidic valves 216a, 216b, 216c, 216d, 216e, and 216f. The microfluidic valve membrane 240 can be attached to the top portion of the microfluidic cartridge 200 by an adhesive device known in the art. The microfluidic valve membrane 240 covers and seals the microfluidic portion 210 of the microfluidic cartridge 200. In some embodiments, the microfluidic valve membrane 240 (and the microfluidic valves 216) are made of a material that expands and changes its shape in response to a stimulus (e.g., temperature). In some embodiments, only the microfluidic valve 216 portion is made of a material that expands and changes its shape in response to a stimulus (e.g., temperature), and the remaining portion of this part of the microfluidic valve membrane 240 uses other suitable materials. In this example, the entire microfluidic valve membrane 240 is made of a paraffin film. In still some other embodiments, the microfluidic valve membrane can be made of polyurethane and / or nylon. The microfluidic valves 216a, 216b, 216c, 216d, 216e, and 216f are planar and respectively seal the inlet / outlet junctions 218a (not shown), 218b, 218c, 218d, 218e, and 218f of the corresponding reagent reservoirs (not shown) in a normally closed state. When the microfluidic valve is exposed to heat, the material of the microfluidic valve expands and changes to a dome shape (i.e., the open state), thereby respectively allowing fluid communication between the inlet / outlet junctions 218a (not shown), 218b, 218c, 218d, 218e, and 218f. In some exemplary embodiments, the opening of the microfluidic valve is irreversible, that is, the microfluidic valve is disposable and cannot be closed again after opening. In yet another exemplary embodiment, the opening of the microfluidic valve is reversible. In some exemplary embodiments, the microfluidic valve membrane can be transparent or translucent, thereby allowing the user to observe the flow of fluid in the microfluidic cartridge 200. In another exemplary embodiment, the microfluidic valve region can be dark (e.g., black) in order to better absorb light energy (and thus heat energy). In this example, the microfluidic valves are represented as black dots on the microfluidic valve membrane. In this example, the detachable sample cover 212 is shaped to match the diameter of the inlet of the sample reservoir 211. The diagnostic portion 220 is in fluid communication with the microfluidic portion 210 through an opening, an inlet 226, and an outlet 228, respectively. In this example, the reactants can be disposed on the diagnostic chip 222 within the enclosed region of the diagnostic chamber.

[0275] In some embodiments, the microfluidic cartridge 200 can include a microfluidic valve membrane, a top portion, at least one adhesive layer, a plurality of micropumps, a microporous membrane, and a bottom portion. Now refer to Figure 11C , which shows Figure 11AExploded view of the same exemplary embodiment. For clarity, some identical or similar elements are present in this microfluidic cartridge, but only one of them is annotated as an example. In this example, the microfluidic cartridge 200 includes a microvalve membrane 240 having a plurality of microvalves (e.g., 216b), a top portion 250, an adhesive layer 270, a plurality of micropumps (not shown), a microporous membrane 260, and a bottom portion 290, which are assembled together as a single unit using an adhesive material or through a welding process. The microvalve membrane 240 can be a thin film made of a paraffin film. In still some other embodiments, the microvalve membrane 240 can be made of polyurethane and / or nylon. The microvalve membrane 240 receives thermal energy as a control signal provided by a microvalve controller of a microfluidic cartridge driver unit (not shown; to be described later) to control the opening of the microvalve during use. When a sufficient light control signal is received at a specific microvalve location on the microvalve membrane 240, the microvalve changes its viscosity. The change in viscosity causes the shape of the microvalve to change from a planar shape to a dome shape, thereby allowing the microvalve to open. Light control signals can be emitted at different times at different valve locations to control the order of reagent release. The top portion 250 includes a sample inlet 212, a plurality of reagent inlets (e.g., 219b), multiple pairs of inlet / outlet junctions (e.g., 218b), and a tape 224. The tape 224 can be made of plastic (e.g., acrylic, polycarbonate), and it defines a diagnostic chamber within the diagnostic portion 220. The reagent inlet 219b forms a fluid inlet in fluid communication with a reservoir (not shown) provided on the opposite side of the top portion 250. The adhesive layer 270 is a plastic film having a certain thickness, which is made of a plastic material (e.g., polycarbonate) coated with an adhesive material on both opposite sides, thereby providing an adhesive force to join the top portion 250 and the bottom portion 290 together. The adhesive layer 270 has a certain thickness and includes a plurality of grooves (e.g., 271b), which are cavities for the space of the reservoirs for accommodating reagents and samples. Each groove (e.g., 271b) has a position corresponding to the respective position of the reservoir, thereby allowing the reservoir to be in direct contact with the next layer (i.e., the bottom portion 290). The substrate of the bottom portion 290 can be made of an electrically insulating material, such as plastic and resin materials. The bottom portion 290 has a groove 291 for placing the microporous membrane 260 therein. The bottom portion 290 also includes a plurality of electrical connection interfaces (not shown) electrically connected to the device and a plurality of conductive traces (e.g., 294b). The space formed between each conductive trace (e.g., 294b) and each corresponding groove (e.g., 271b) allows a hydrogel to be placed therein. The electrical connection interfaces are electrically connected to the conductive traces. The conductive traces (e.g., 294b) can be in direct or indirect contact with a hydrogel (not shown).

[0276] Still referring to Figure 11C, the top portion 240 can be made of acrylic, polycarbonate, or similar types of plastic materials. It can be transparent or partially transparent to allow the user to observe the state of the fluid inside the microfluidic portion 210. The plastic portion can be manufactured by a plastic injection process associated with other processes (e.g., hot embossing and micromachining methods). The top portion 250 includes a plurality of cavities (e.g., 271b) corresponding to a plurality of reservoirs (not shown), where at least one reservoir is configured to hold a sample from the top portion, and at least one reservoir is configured to hold at least one reagent to facilitate the reaction or interaction between the analyte interacting molecules and the analyte. Thus, the detection of the analyte can be promoted. The reagent held in at least one reservoir can be a wash buffer or a blocking buffer. The sample is driven from the microfluidic portion 210 to the diagnostic portion 220 for analyte reaction / interaction on the diagnostic chip 222. The reagent and the sample are driven from the microfluidic portion 210 to the diagnostic portion 220 through microfluidic channels (not shown), and then to the inlet 226.

[0277] Each reservoir (not shown) is integrated with a micropump constructed with a small amount of hydrogel (not shown) placed therein. The hydrogel contacts a conductive trace (e.g., 294b) bonded to the construction material of the bottom portion 290. These micropumps are operated by an electric current supplied through the conductive trace (e.g., 294b). These micropumps push the sample and the reagent through the microfluidic channels by expanding and contracting the hydrogel, thereby driving the sample and the reagent to the channel openings. The expansion and contraction of the hydrogel are controlled by the microfluidic cartridge driver unit 320 of the diagnostic device by sending signals and power through the connection between an electrical connection interface (not shown, on the bottom opposite side of the bottom portion) and the conductive trace (e.g., 294b). In some embodiments, the hydrogel of the micropump is encapsulated so that contamination and cross - contamination problems can be avoided. In still some other embodiments, the hydrogel of the micropump can be in direct contact with the fluid (e.g., reagent or sample) inside the reservoir. In some embodiments, the microfluidic cartridge further includes a micropump membrane for sealing the hydrogel. The microvalve membrane also covers all reservoirs to prevent fluid leakage. The micropump diaphragm also helps to push the fluid out of the reservoir by the action of the micropump of the microfluidic cartridge. The micropump membrane can include grooves of a microporous membrane, thereby allowing the microporous membrane to be in direct contact with the surrounding environment. In one exemplary embodiment, the volume of each reservoir (not shown) is in the range of 20 - 150 μl. In another exemplary embodiment, the volume of each reservoir (not shown) is in the range of 20 - 200 μl. In one exemplary embodiment, the number of reservoirs in a microfluidic cartridge is 5 - 12. In one exemplary embodiment, a detachable sample cap 212 is provided at the opening for sample introduction to prevent leakage or evaporation of the sample (see Figure 11C ).

[0278] Each conductive trace (e.g., 294b) of the microfluidic cartridge 200 is associated with a specific reservoir. When connected, an electrical pulse from the electrical connection interface passes through the conductive trace and electrolyzes the hydrogel in the specific reservoir. The electrolysis process produces oxygen and hydrogen, and these gases expand to push the fluid inside the reservoir out of the reservoir. The valve at the reservoir outlet is sealed with a plastic film, but upon irradiation, the valve opens and allows the reagent in the reservoir to be pushed into the microchannel / the next reservoir (depending on the location of the outlet connection). The flow rate of the reagent is controlled by an electrical pulse sequence that is transmitted to the conductive traces in the bottom portion 290 of the microfluidic cartridge 200.

[0279] The diagnostic chip 222 can be made of glass, silicon, or plastic and is fixed to the diagnostic portion. The bottom surface of the diagnostic chip 222 (i.e., the surface facing the channel opening) pre-coated with an array of detection points is disposed toward the channel opening and is in fluid communication with the channel opening. The detection point array can react / interact with the analyte present in the sample to generate at least one signal under certain conditions (e.g., generate one or more fluorescence signals when irradiated with a laser of a certain wavelength). In one embodiment, each of these detection points contains at least one analyte-interacting molecule that reacts / interacts with at least one analyte. In a particular embodiment, the analyte-interacting molecule is a specific protein or peptide that binds to at least one specific virus / bacterium (e.g., antigen) in its intact state or in a partially suitable form for detection. The detection point array is located at the diagnostic chip 222 of the diagnostic portion such that when the sample and reagent are pumped into the inlet 226( Figure 11B ), they can be dispersed through the array. The bottom surface of the diagnostic chip 222 is first coated with a first coating that is used to immobilize the subsequently coated detection points without changing the configuration of the detection points (e.g., maintaining the binding sites of the analyte-interacting molecules contained in the detection points to make them accessible to one or more analytes). The first coating should also create a hydrophilic environment for the analyte to react / interact. It is optimized to minimize non-specific reactions / interactions and thus reduce the background noise signal in this device. Once the first coating is completed, the detection points are deposited on the bottom surface of the diagnostic chip 222 in a predetermined pattern (e.g., an array). The drop-on-demand method is selected to disperse them onto the diagnostic chip 222. In one embodiment, the drop-on-demand method can be performed by a microarray printer. In some embodiments, the microfluidic cartridge is pre-supplied with at least one reagent and / or at least one reactant, and it is disposable. In some embodiments, the microfluidic cartridge includes multiple reservoirs for storing reagents, samples, and waste. The reservoirs can be in fluid communication with the microchannels.

[0280] Example 7

[0281] Now refer to Figure 12A - 12F, which shows another exemplary embodiment of the microfluidic cartridge 200. Figure 12A A exploded view showing an exemplary embodiment of the microfluidic cartridge 200 is shown. This figure shows how to assemble the microfluidic cartridge using different layers of materials. In this exemplary embodiment, the microfluidic cartridge 200 is assembled with a microvalve membrane 240 on top, followed by a top portion 250, a first adhesive layer 270a, a microporous membrane 260, a micropump membrane 280, a second adhesive layer 270b, and a bottom layer 290 in sequence. The top layer 250 further includes a microfluidic portion having a sample lid 212 and a diagnostic portion having a tape 224 and a diagnostic chip 222. The tape 224 is configured to form a diagnostic chamber (not shown) in the diagnostic portion 220 having the diagnostic chip 222. In some exemplary embodiments, the microfluidic cartridge 200 includes a microfluidic portion 210 and a diagnostic portion 220, wherein the microfluidic portion 210 includes a plurality of reservoirs (not shown) capable of holding fluid therein, a plurality of microchannels (not shown) for fluid connection from the reservoirs to the diagnostic portion 220, a plurality of microvalves 216 operable between a closed state and an open state to respectively seal and open the microchannel connections, and at least one micropump coupled to at least one reservoir; wherein the microvalve 216 in the closed state allows the fluid to be stored and sealed within the reservoir, while the microvalve 216 in the open state allows the fluid to flow between the reservoir and the diagnostic portion 220; and wherein the micropump can be actuated to move the fluid from the reservoir to the diagnostic portion, such that a variety of reagents can be pre-loaded and stored in the microfluidic cartridge 200 in a sealed manner until use. A notch is provided in one corner of each layer.

[0282] Figure 12B Shows Figure 12A A detailed view of the microvalve membrane of the same exemplary embodiment of. In this example, the microvalve membrane 240 is a membrane having six microvalves 216g, 216h, 216i, 216j, 216k, and 216l. The microvalve membrane 240 can be at least partially made of a paraffin film and attached to the top portion 250 of the microfluidic cartridge 200 by any adhesion means known in the art (as shown in Figure 12C ). In still some other embodiments, the microvalve membrane can be made of polyurethane and / or nylon. After the reagent is loaded or supplied through an inlet (not shown), the microvalve membrane 240 can be fixedly attached to the top to seal the reagent for storage until use during the manufacturing process. The membrane covers and seals the microfluidic portion 210 of the microfluidic cartridge 200. In some embodiments, the microvalve membrane 240 (and the microvalve 216) is made of a material that expands and changes its shape in response to a stimulus (e.g., temperature), as described in the previous example. The microvalves 216g, 216h, 216i, 216j, 216k, and 216l are planar and respectively seal the corresponding reagent reservoirs in a normally closed state (as shown in Figure 12DThe corresponding inlet / outlet nodes 218g, 218h, 218i, 218j, 218k, and 218l (as shown in ). In this exemplary embodiment, when the microvalves 216g, 216h, 216i, 216j, 216k, and 216l are exposed to heat, the materials of the microvalves 216g, 216h, 216i, 216j, 216k, and 216l expand and change to a dome shape (i.e., the open state), thereby allowing fluid communication between the inlet / outlet nodes 218. In some exemplary embodiments, the opening of the microvalve is irreversible, that is, the microvalve is for single use and cannot be closed again after opening, thus avoiding the user from reusing the microfluidic cartridge. In yet another exemplary embodiment, the opening of the microvalve is reversible. In some exemplary embodiments, the microvalve membrane can be transparent or translucent, thereby allowing the user to observe the flow of the fluid in the microfluidic cartridge 200. In another exemplary embodiment, the microvalve region can be dark (e.g., black) in order to better absorb light energy (and thus heat energy). In this example, the microvalves 216g, 216h, 216i, 216j, 216k, and 216l are represented as black dots on the microvalve membrane.

[0283] Figure 12C and Figure 12D respectively show Figure 12A the detailed structures of two opposite sides of the top portion 250 of a sample exemplary embodiment. In the same exemplary embodiment, the top portion 250 includes a microfluidic portion 210 and a diagnostic portion 220 in one corner near the notch. In some exemplary embodiments, at least one reservoir is filled with at least one fluid, where the fluid is a reagent and is sealed with a microvalve. In some exemplary embodiments, at least one reservoir for holding at least one sample further includes a sample inlet 217 having a detachable lid. In some exemplary embodiments, the microfluidic cartridge further includes a variety of reagents pre-loaded, sealed, and stored in multiple reservoirs respectively; and at least one reactant pre-supplied at the diagnostic portion. Each reservoir has an inlet and an outlet, which can be connected through fluid channels. The microfluidic portion 210 includes a sample inlet 217 (as shown in ) that can be sealed by a sample lid 212 and a microchannel extending from the sample inlet 217 (as shown in ). In this example, the microfluidic portion 210 also includes a reservoir 213n (or sample reservoir) for holding the introduced sample, six reservoirs 213g, 213h, 213i, 213j, 213k, and 213l (or reagent reservoirs) for storing reagents, and a reservoir 213m (or waste reservoir) for holding waste. The reservoir can be in a tubular form of any desired shape, such as Figure 12A as shown in Figure 12D and a microchannel extending from the sample inlet 217 (as shown in Figure 12DThe S-shape shown in. At one end of the sample reservoir 213n, there is a microchannel (after passing through the microporous membrane) that is in fluid communication with the sample inlet 217, and at the other end of the sample reservoir 213n, there is another microchannel that is connected from other (reagent) reservoirs to other microchannels. The reagent reservoirs 213g, 213h, 213i, 213j, 213k, and 213l each include inlets 219g, 219h, 219i, 219j, 219k, and 219l at one end, which can introduce at least one reagent into the corresponding reservoir. At the other end of the reagent reservoir, there are inlet / outlet nodes 218g, 218h, 218i, 218j, 218k, 218l, which are correspondingly sealed by the corresponding microvalves 216g, 216h, 216i, 216j, 216k, and 216l (as Figure 12B shown in). Each pair of inlet / outlet nodes 218 includes the outlet of the reagent reservoir and the inlet of a microchannel that is connected to other parts of the microfluidic section. The microchannels connect the sample reservoir and / or the reagent reservoir to the diagnostic section. These reservoirs can be interconnected by microchannels. In this example, the microfluidic section 210 also includes the sample reservoir 213n, and the detachable sample lid 212 is shaped to match the diameter of the inlet of the sample reservoir 213n. The diagnostic section 220 is in fluid communication with the microfluidic section 210 through the inlet 226 and the outlet 228. In some embodiments, the microfluidic cartridge further includes at least one reservoir for holding waste. In some embodiments, the microfluidic section further includes a waste reservoir 213m, where the waste reservoir 213m is connected to the diagnostic section via an outlet to accommodate the waste fluid discharged from the diagnostic chamber. Figure 12D is shown Figure 12C opposite sides of the top portion of the same exemplary embodiment of. In this example, the fluid channels are microchannels. In some embodiments, the reservoirs can be configured to form chambers for holding fluids and can have any desired shape and form. In this example, the reservoirs are designed in an S-shape to save space, such that the microfluidic cartridge can be compact and of small size. In some embodiments, the diagnostic section includes a diagnostic chamber to accommodate at least one fluid from the microfluidic section. In some embodiments, the diagnostic section is at least partially transparent for optical detection.

[0284] Now referring back to the Figure 12A, which shows a first adhesive layer 270a. In this example, the first adhesive layer 270a attaches the bottom (opposite) side of the top portion 250 to the top side of the microporous membrane 260 and the micropump membrane 280. The first adhesive layer 270a can be made of any suitable plastic material (e.g., polycarbonate) with an adhesive material coating on both opposite sides. In this exemplary embodiment, the first adhesive layer 270a has a certain thickness and includes seven grooves 271a, which are cavities for the spaces of the reservoirs for accommodating reagents and samples. The thickness of the adhesive layer 270a can correspond to the thickness of the reservoirs in the top portion. The positions of the grooves 271a correspond to the respective positions of the reservoirs, allowing the reservoirs to be in direct contact with the next layer (i.e., the micropump membrane 280). In some embodiments, the microfluidic cartridge 200 further includes a microporous membrane configured to remove gas from a fluid (e.g., a sample and / or one or more reagents). The first adhesive layer 270a also includes a plurality of microchannel openings 272 (five microchannel openings, as Figure 12A shown). The microchannel openings 272 serve as connecting channels for transporting fluid between the discontinuous microchannels in the top portion 250. The microchannel openings 272 form fluid channels to connect the microchannels in the top portion 250 and the microporous membrane 260, allowing fluid (e.g., sample, reagent, and waste) to pass through the microporous membrane 260, thereby removing any air bubbles in the fluid. The microporous membrane 260 can be made of any hydrophobic material (e.g., PTFE) that is permeable to gas but impermeable to liquid.

[0285] Figure 12A The micropump membrane 280 is also shown, which is disposed between the first adhesive layer 270a and the second adhesive layer 270b, allowing for direct attachment between the top portion and the bottom portion. The micropump membrane 280 serves as a separator between the reservoir and the micropump, thus preventing the hydrogel in the micropump from coming into direct contact with the fluid (e.g., sample and reagent). The micropump membrane 280 also includes a groove 283, which is a cavity for the space for accommodating the microporous membrane 260, allowing the microporous membrane 260 to be in direct contact with the surrounding environment. The micropump membrane 280 can be made of a paraffin film or plastic (e.g., polyurethane and / or nylon). The micropump membranes 280 cover all the reservoirs to prevent fluid leakage. They work with the micropump to push the fluid out of the reservoirs by the action of the micropump of the cartridge.

[0286] Figure 12AA second adhesive layer 270b is also shown. In this example, the second adhesive layer 270b attaches the opposite side of the micropump membrane 280 to the bottom portion 290. Any suitable adhesive material can be used to fabricate the second adhesive layer 270b. In this exemplary embodiment, the second adhesive layer 270b has a certain thickness and includes seven grooves 271b, which are cavities for accommodating the space of the micropump. The thickness of the adhesive layer 270b can correspond to the thickness of the micropump. In this example, a hydrogel (not shown) is used as the micropump and is disposed within the grooves 271b of the second adhesive layer 270b. The positions of the grooves 273 correspond to the respective positions of the reservoirs, allowing the reservoirs to be in direct contact with the next layer (i.e., the micropump membrane 280), such that the micropump of the microfluidic cartridge 200 can act on the reservoirs to push fluids (e.g., samples and reagents) out of the reservoirs.

[0287] Now referring to Figure 12E and 12F , which shows Figure 12A two opposite sides of the bottom portion 290 of the same exemplary embodiment of the microfluidic cartridge. The bottom portion 290 can be made of an electrically insulating material (e.g., plastic and resin materials). The bottom portion 290 of the microfluidic cartridge has a groove 291 for placing the microporous membrane 260 therein. The bottom portion 290 also includes a plurality of conductive circuit traces 294g, 294h, 294i, 294j, 294k, and 294l ( Figure 12E ), which are electrically connected to the electrical connection interfaces 293 on the opposite sides of the bottom portion 290. The electrical connection interfaces 293 transmit electricity from the device to the microfluidic cartridge 200 to activate the micropump. A micropump (not shown) constructed with a small amount of hydrogel is juxtaposed with the corresponding reservoir (see Figure 12D)。The hydrogels of the micropumps 215 are in contact with their respective conductive circuit traces 294g, 294h, 294i, 294j, 294k, and 294l, which are bonded to the construction material of the bottom portion 290. These micropumps are operated by an electric current supplied through the conductive circuit traces 294. When receiving the electric current, the conductive traces 294g, 294h, 294i, 294j, 294k, and 294l conduct electricity to electrolyze the hydrogel, thereby generating gases that push the micropump membranes 280 upward, thus pushing the fluid out of the reservoir. These micropumps push the sample and reagent through the microchannel, thereby mixing the sample and reagent into the microchannel by expanding and contracting the hydrogel. The expansion and contraction of the hydrogel are controlled by the cartridge drive unit of the portable diagnostic device 300 by sending signals and power through the connection between the electrical connector of the cartridge receiving unit 310 and the electrical connection interface 293 of the bottom portion 290, which is also electrically connected to the conductive circuit traces 294g, 294h, 294i, 294j, 294k, and 294l of the bottom portion 290. In some embodiments, the micropumps are encapsulated so that contamination and cross - contamination issues can be avoided. In some embodiments, these pumps are in direct contact with the fluid (e.g., reagent or sample) within the reservoir. In some embodiments, the microfluidic cartridge further includes a micropump membrane for sealing the hydrogel. In the present example, the microfluidic cartridge 200 includes a micropump membrane 280 that covers the entire area of the reservoir to prevent any fluid leakage and direct contact between the hydrogel and the fluid within the reservoir. The bottom portion 290 also includes an inductive sensing element 292( Figure 12E ), which is juxtaposed to the area of the waste reservoir to detect the presence and amount of the fluid flowing into the waste reservoir using capacitance sensing technology.

[0288] Example 8

[0289] Now refer to Figure 13A and 13B, which shows how an exemplary microfluidic cartridge 200 operates during use. For clarity and simplicity, only one set of reagent reservoirs, microvalves, hydrogels or micropumps, and inlet / outlet junctions are shown. During the manufacturing process, each reagent is first loaded or supplied through a reagent inlet 219 into a reagent reservoir 213. Then, the surface of the top portion 250 having the reagent inlet 219 is sealed by a microvalve membrane 240 to prevent fluid leakage from the reagent inlet 219 and outlet 218' of the reservoir 213. The valve seat 252 can be configured to support the microvalve 216 so that it does not collapse in the stationary state. The valve seat 252 is located between the reservoir 213 and the fluid microchannel 214 to separate the two compartments, such that when the microvalve 216 is in the closed state, the fluid in the reservoir 213 cannot flow through the fluid microchannel 214. The outlet 218' and the inlet 218" form an inlet / outlet junction, which is sealed by the microvalve 216. The microvalve 216 on the present microvalve membrane 240 is arranged side by side with each pair of fluid inlet and outlet junctions (218' and 218") of the top portion 250. A reactant (e.g., an antibody) can be pre-coated on a diagnostic chip 222 within the enclosed area of the diagnostic chamber 221 formed with a tape 224. Different parts (i.e., the microvalve membrane 240, the top portion 250, the adhesive layers 270a, 270b, the micropump membrane 280, the microporous membrane 260, and the bottom portion 290) of the microfluidic cartridge 200 are assembled together by an adhesive means or a welding process. The microfluidic cartridge 200 can be sealed and packaged for shipping.

[0290] When in use, a fluid-containing sample is introduced into the microfluidic cartridge 200 by opening the sample lid and introducing the sample through a sample inlet (not shown). Appropriate sample preparation can be performed before sample introduction. The sample flows into the microchannel and reaches the microchannel opening. At the microchannel opening, the sample contacts the microporous membrane to remove any air bubbles in the fluid. Then, the sample enters the microchannel and flows into the diagnostic chamber 221.

[0291] At this time, the sample and the reagent reservoir will be correspondingly filled with all the necessary samples and reagents. Then, an electric current from a microvalve controller and a micropump controller is applied to the microfluidic cartridge 200 to activate the microvalve 216 and the hydrogel 2152 of the micropump of the microfluidic cartridge 200. Now refer to Figure 13B, a heating element of a microvalve controller (not shown) disposed on the microvalve 216 emits energy (e.g., infrared rays) towards the microvalve 216 to open the microvalve 216. This event puts the fluid microchannel 214 in fluid communication with the reservoir 213 and the diagnostic chamber 221. The micropump contains a hydrogel 2152 that is in direct or indirect contact with the conductive trace 294. The conductive trace 294 receives current from the device through an electrical connection interface (not shown) to the hydrogel 2152 in a predetermined sequence. Electrical pulses pass through the conductive trace 294 and electrolyze the hydrogel 2152 in the specific reservoir 213. The electrolysis process produces oxygen and hydrogen, and these gases expand, causing the chamber holding the hydrogel 2152 to expand, thereby causing the micropump membrane 280 to push the fluid (sample and / or reagent) inside the reservoir 213 out of the reservoir 213 in a controlled and precise manner. This fluid is pushed out of the reservoir 213 and enters the microchannel 214 through the fluid outlet 218' and inlet 218" junctions. Figure 13B The arrows in

[0292] show the fluid flow direction. Then, the fluid reaches another microchannel opening 272a. At the microchannel opening 272a, the fluid contacts the microporous membrane 260 to remove any air bubbles. Then, the fluid enters another microchannel and flows into the diagnostic chamber 221, which is the detection area.

[0293] Then, an optical inspection of the diagnostic part is prepared.

[0294] Example 9

[0295] Portable Diagnostic Device

[0296] Now refer to Figure 14A , an exemplary embodiment of the diagnostic system 101 includes a portable diagnostic device 300 and a microfluidic cartridge 200 that operates with the portable diagnostic device 300. In this example, the diagnostic device 300 includes a control unit 340, a microfluidic cartridge drive unit 320, an optical unit 330, a user interface unit 350, a cartridge housing unit 310, and a power supply unit 360. The portable diagnostic device 300 is enclosed in a housing 301, where the housing 301 includes a top cover 351, side covers 352 and 353, a rear cover 354, a front panel 355, and a base 356. In some exemplary embodiments, the optical unit 330 includes an illumination assembly 331 and a sensor assembly 332. The illumination assembly includes a light source 331A, a light pipe 331B, and a filter 331C. The sensor assembly includes a camera 332A, a camera lens 332B, and an objective lens 332C.

[0297] Now refer to Figure 14B, Another exemplary embodiment of the diagnostic system 101 includes a portable diagnostic device 400 and a microfluidic cartridge (not shown) that operates with the portable diagnostic device 400. In some exemplary embodiments, the portable diagnostic device 400 may include all of the units in the portable diagnostic device 300. In some exemplary embodiments, the portable diagnostic device 400 includes a cartridge drive unit 420, an optical unit 430, a display unit 450, a cartridge receiving unit 410, a power supply unit 460, and an identification unit 470. In one exemplary embodiment, the portable diagnostic device 400 optionally includes a control unit 440. The control unit 440 controls and is operably connected to the cartridge drive unit 420, the optical unit 430, and the display unit 450. In some other exemplary embodiments, each unit may have its own control unit, and there is no single control unit in the portable diagnostic device. In one exemplary embodiment, the microfluidic cartridge drive unit includes a microvalve controller 421 and a micropump controller 422. When the microfluidic cartridge is placed in the cartridge receiving unit 410, the microvalve controller 421 and the micropump controller 422 can cooperate to actuate the fluid to flow from the reservoir to the diagnostic section in a predetermined order. In one exemplary embodiment, the cartridge receiving unit 410 includes a tray 411 and a track assembly 412. In this example, the tray 411 is slidably removable from the cartridge receiving unit 410. The track assembly 412 is fixedly attached to the portable diagnostic device 400 and is configured to receive the tray 411. In this example, in Figure 14B an assembly 480 of the cartridge receiving unit 410, the optical unit 430, and the identification unit 470 is shown to illustrate the configuration and spatial relationship between these units. In Figure 18 a detailed description of the assembly 480 is disclosed.

[0298] In one exemplary embodiment, the portable diagnostic device 400 is enclosed in a housing 401, where the housing 401 includes a top cover 451, side covers 452 and 453, a rear cover 454, a front panel 455, and a base 456. In this exemplary embodiment, the track assembly 412 of the cartridge receiving unit 410, the microfluidic cartridge drive unit 420, the optical unit 430, and the identification unit 470 are installed in the housing in a certain configuration such that when the microfluidic cartridge is inserted into the device, there is a space (not shown) for receiving the microfluidic cartridge. This space includes one or more microvalve positions and one or more micropump positions. This space also contains reaction positions that correspond to the positions of one or more microvalves, one or more micropumps, and reaction sites when the microfluidic cartridge is inserted into this space. In Figure 18 a more detailed description of this space is provided. In one exemplary embodiment, the front panel 455 of the housing includes a microfluidic cartridge receiving cavity 455A. The microfluidic cartridge is inserted into the space through the receiving cavity 455A.

[0299] In some exemplary embodiments, the control unit 440 may have the same configuration as the control unit described in the previous examples. The control unit 440 controls the quantitative and qualitative analysis, interface connection, and storage of signals obtained from the optical unit 430, and controls and monitors all operations of the portable diagnostic device 400.

[0300] In some exemplary embodiments, the power supply unit 460 may have the same configuration as the power supply unit described in the previous examples. In some exemplary embodiments, the power supply unit 460 may include a built-in or removable rechargeable battery.

[0301] In one exemplary embodiment, the portable diagnostic device 400 may further include at least one USB port or any other data communication device in the data communication port 455B to allow operation of a general data transfer communication protocol. In yet another exemplary embodiment, a display unit 450 is provided in the portable diagnostic device 400 for a human-machine interface. The display unit 450 is a high-resolution color display, which may be a liquid crystal display (LCD), an organic light-emitting diode (OLED), or other types of displays. The display unit 450 may be combined with a touch screen panel; thus, it can receive commands from a human finger touch. The display unit 450 is connected to the control unit 440. However, the way it displays the displayed content is through a graphical user interface.

[0302] Now refer to Figure 15A As shown in Figure 14B , the micro-valve controller 421 of the cartridge drive unit 420 includes a substrate 530 having a flat surface that is cut into a shape suitable for a cartridge chamber (not shown in this figure). And a plurality of nuts 510 and slots 520 are provided thereon. In this exemplary embodiment, screws (not shown) within the nuts 510 are used to firmly mount the micro-valve controller 421 to the Figure 14B track assembly 412 of the cartridge receiving unit 410 in

[0303] Now refer to Figure 15B, the microvalve controller 421 includes a plurality of heating elements 541 (six in this example) disposed on and extending outwardly from the bottom surface of the substrate 530. The heating elements 541 are located on the substrate to coincide with the microvalves of a cartridge (not shown in this figure), and the device is designed to operate on such a cartridge. When the substrate 530 is fixed in place, it is directly above the cartridge chamber (not shown in this figure), and when the cartridge is properly inserted into the device and positioned in the designated area, each heating element 541 will be directly above each microvalve. The heating elements 541 are configured to apply thermal energy to the thermally deformable surface of the microvalve to open the microvalve. In some embodiments, the heating elements 541 are electromagnetic radiation emitters configured to emit electromagnetic radiation as an energy source. In some additional exemplary embodiments, the heating elements 541 are IR emitters configured to emit infrared (IR) light as a thermal energy source.

[0304] Now referring to Figure 16A , the cartridge receiving unit 410 includes a tray 411 and a track assembly 412. In the illustrated exemplary embodiment, the track assembly 412 includes a flat tray cover 1520 (also referred to as a tray plate in some embodiments) and two side walls 1521 that define a partially enclosed compartment. The track assembly 412 includes a space having a volume greater than the volume of the tray 411 for slidably receiving the tray such that when the tray 411 with a microfluidic cartridge inserted therein slides to the docking position, the microfluidic cartridge is located in the designated area for reaction and detection. In some embodiments, the track assembly 412 is fixedly attached to the portable diagnostic device 400 and is configured to receive at least two edges of the tray 411.

[0305] In the illustrated exemplary embodiment, a pair of slidable tracks 1510 are disposed on the inner sides of the opposing side walls 1521. In Figure 16A only one track 1510 is shown, but it should be understood that there is another track on the opposite side of the inside of the side wall 1521. The tray 411 can be anchored on the pair of tracks 1510. The pair of tracks 1510 slide the tray 411 into or out of the space as described above.

[0306] In one exemplary embodiment, the track assembly 412 further includes a microvalve controller cover 1522 that is fixedly attached to the top surface of the tray cover 1520 to hold Figure 15A and 15B the microvalve controller 421 therein. In some exemplary embodiments, the microvalve controller cover 1522 can be an integral part of the tray cover 1520 rather than a separate part. The microvalve controller cover 1522 provides means for supporting the microvalve controller 421. In the present exemplary embodiment, by fastening a screw 1523 to the nut 510 of the microvalve controller 421 (asFigure 15A As shown in Figure 14B , three screws 1523 are used to securely mount the micro-valve controller 421 under the micro-valve controller cover 1522. In one exemplary embodiment, the micro-valve controller cover 1522 forms a raised platform 1525 that extends upward from the top surface of the tray cover 1520. The raised platform 1525 has a shape that includes an opening located above the slot 520 of the micro-valve controller 421 to allow one or more wires connected to the slot to pass through. The raised platform 1525 further includes an opening that is in the cartridge insertion space and is located above a 2D code attached to a microfluidic cartridge (not shown in this figure) when the cartridge is positioned in a designated area in the device. This opening ensures that when the cartridge is positioned in the designated area in the device, the identification unit 470 (as shown in

[0307] Now referring to Figure 16B , which shows Figure 16A another perspective view of the same cartridge receiving unit 410 as in Figure 16B . In one exemplary embodiment, the tray cover 1520 has an opening 1524 (partially shown) for receiving the micro-valve controller 421 thereon. The opening 1524 is sized greater than or equal to the size of the microfluidic cartridge and is divided into three regions: a first region 1524A, a second region 1524B, and a third region 1524C. In another exemplary embodiment as shown in Figure 15B , the second region 1524B can be a separate opening. The micro-valve controller is positioned adjacent to the first region 1524A such that when the microfluidic cartridge is inserted into the tray 411 and the tray 411 is slid to the docking position, the micro-valve on the microfluidic cartridge is directly positioned under the micro-valve controller 421. As described in

[0308] In some exemplary embodiments, the cartridge receiving unit 410 further includes a switch 1526. In another exemplary embodiment, the switch is a microswitch. The microswitch may be attached to the back of the rail assembly 412 and electrically connected to a power supply unit (not shown). When the tray 411 with the microfluidic cartridge inserted therein slides to the docking position through the rail assembly 412, the microswitch is automatically activated. After activation, the microswitch may turn on an identification unit (not shown) to read the identification of the microfluidic cartridge and automatically select the program to be used.

[0309] Figure 16C shows a Figure 16A schematic diagram of the tray 411 of the cartridge receiving unit 410 in Figure 16D shows the same tray 411 but with a Figure 11A microfluidic cartridge 200 inserted therein from

[0310] The tray 411 serves as the same location for performing: (1) reactions to be run in a predetermined order and (2) optical analysis of the microfluidic cartridge. In one exemplary embodiment, the tray 411 includes an electrical connector 3211 disposed on the cartridge chamber 1530 of the tray. The electrical connector 3211 is configured to receive a control signal and power from the micropump controller 422 as shown in Figure 14B to perform a predetermined sequence by supplying current to the micropump of the microfluidic cartridge 200. In one exemplary embodiment, when the cartridge is inserted into the chamber 1530, the electrical connector 3211 is located below the microfluidic cartridge 200. The electrical connector 3211 is electrically connected to the electrical connection interface of the cartridge 200 and serves as an interface for the cartridge driver unit 420 to drive and control the micropump in the cartridge 200. In another exemplary embodiment, the tray 411 includes an opening 1543 on the cartridge chamber of the tray 411. The opening 1543 is configured such that it is directly below the diagnostic portion 210 of the cartridge 200 when the cartridge is inserted and fixed in the chamber 1530, allowing light to pass through the diagnostic portion 210 during optical analysis. The single-tray system eliminates the possibility of human error by design.

[0311] In an exemplary embodiment, the tray 411 further includes an anchoring system to secure the microfluidic cartridge 200 in the tray when inserted therein. In an exemplary embodiment, the anchoring system consists of at least one cartridge clip 1541 disposed on the tray sheet 1540. In another exemplary embodiment, the anchoring system consists of two cartridge clips 1541 and 1542 positioned orthogonally to each other. Once the microfluidic cartridge 200 is inserted into the tray 411, the two clips work together to restrict its movement. Less movement means less variation in the possible location of the biometric, thus increasing detection accuracy and precision. The addition of additional cartridge clips reduces the tolerance to 0.1 mm and enables more accurate detection as the variation in biometric location is minimized. In an exemplary embodiment, the tray 411 further includes at least one tray clip 1544 disposed on the tray sheet 1540 to secure the position of the tray as it slides in the cavity of the track assembly 412 (as Figure 16A shown).

[0312] Now refer to Figure 17, the optical unit 430 includes an illumination assembly 1610 and a sensor assembly 1620. In some embodiments, the illumination assembly 1610 includes at least one light source 1611 and an optical tube 1612. In some embodiments, the optical unit 430 further includes one or more filters 1613. In some exemplary embodiments, the one or more filters 1613 are contained in a filter cube. In one exemplary embodiment, the sensor assembly 1620 includes a camera 1621 located at the top of the optical unit 430, a camera lens 1622 located below the camera 1621, and at least one objective lens 1623. In some exemplary embodiments, the optical unit 430 further includes a camera base mount 1624 located between the camera 1621 and the camera lens 1622 to connect the two components. In some exemplary embodiments, the optical unit 430 further includes a filter mount 1625 configured to connect the camera lens 1622, the one or more filters 1613, and the objective lens 1623. In one exemplary embodiment, the filter mount 1625 is shaped to include a cavity to accommodate the one or more filters 1613 such that the one or more filters 1613 can be securely assembled within the filter mount 1625. The filter mount 1625 further includes an opening at the top to connect the camera lens 1622 and the one or more filters 1613, an opening at the side to connect the optical tube 1612 and the one or more filters 1613, and an opening at the bottom to connect the objective lens 1623 and the one or more filters 1613. In some exemplary embodiments, the optical unit 430 further includes a box front 1614 configured to connect the illumination assembly 1610 and the filter mount 1625 such that light from the light source 1611 can enter the one or more filters 1613 at a fixed angle. In some exemplary embodiments, the optical unit 430 further includes an objective lens cover 1626 configured to accommodate and secure the objective lens 1623. In some exemplary embodiments, the device further includes one or more stands 1627 that serve as a support to hold the structure of the optical unit 430 when all the components are assembled together. The stand 1627 also serves as a support such that the optical unit 430 and the cartridge receiving unit 410 (as Figure 16A shown) are Figure 18 securely mounted on the stand in the configuration further described in

[0313] When a tray 411 with a microfluidic cartridge 200 inserted therein (shown in Figure 16D but not shown in this figure) is in its docking position in the device, the diagnostic portion 210 of the microfluidic cartridge 200 is directly located below the optical unit 430 for inspection. The illumination assembly 1610 and the sensor assembly 1620 are mounted to point at the diagnostic portion of the microfluidic cartridge. In Figure 18A further description of the arrangement is provided. The illumination assembly 1610 is configured to transmit light to the diagnostic portion 210 of the microfluidic cartridge, and the sensor assembly 1620 is configured to detect at least one signal generated by the diagnostic portion due to the presence of an analyte when the microfluidic cartridge is inserted and operated under predetermined conditions. The optical unit 430 can be used for in-situ analyte analysis / detection. In some embodiments, the device can include one or more optical units 430. The optical unit 430 can acquire an image or a signal of the sample. The optical unit can send the acquired signal to the control unit to convert the acquired signal into a meaningful value.

[0314] In some exemplary embodiments, the light source 1611 can be a monochromatic or polychromatic laser or LED. The light source 1611 should be strong enough to excite the fluorophore. In one exemplary embodiment, the light source 1611 is an LED. In some exemplary embodiments, the light source 1611 can be a high-brightness LED spotlight having a blue or red LED color. In some exemplary embodiments, compared with using blue, green or other colors, using an LED spotlight having a red LED color is advantageous, for example, it is beneficial to reduce the autofluorescence of the microfluidic cartridge (not shown). The red light from the light source 1611 can be collimated with a lens and / or a filter 1613 to filter the appropriate wavelength, reflected by a mirror and focused onto the diagnostic portion of the microfluidic cartridge, and imaged with a detector (e.g., a CCD camera). The red excitation light can excite the red-excitable fluorophore present in the reaction sample on the diagnostic portion. In some exemplary embodiments, other red-excitable fluorophores can be used.

[0315] In another exemplary embodiment, the illumination assembly 1610 includes a light source 1611, such as a diode laser, which radiates at least one laser beam having at least one predetermined wavelength onto the microfluidic cartridge 200 to generate at least one signal. The predetermined wavelength of the laser beam is selected such that at least one signal can be generated that can be detected by the sensor assembly 1620. In one exemplary embodiment, the user can select / control the intensity and wavelength of the laser beam through a control unit (not shown in this figure) to detect a specific analyte. The laser beam is steered at an angle towards the microfluidic cartridge, thereby avoiding reflection and generating a higher-quality signal. The predetermined wavelength is, for example, in the range of 465 to 500 nm, 400 to 700 nm, 430 to 465 nm, 500 to 550 nm, 550 to 580 nm, 580 to 620 nm or 620 to 700 nm.

[0316] In an exemplary embodiment, the light source 1611 includes a light pipe 1612 that emits light uniformly. The light pipe 1612 is configured such that when the cartridge is positioned in a designated area, it guides light to other optical components and helps focus the light beam onto the analyte on the diagnostic portion of the microfluidic cartridge. When the cartridge is positioned in the designated area for reaction and analysis, the light pipe 1612 is aligned with the analyte on the diagnostic portion at a specific location on the microfluidic cartridge. In an exemplary embodiment, the illumination assembly 430 may further include at least one condenser lens (not shown) as described in Example 1, such that the focusing of the light from the light source 1611 is optimized.

[0317] In one embodiment, the optical unit 430 may include one or more light sources, one or more lenses, one or more dichroic mirrors, one or more sensors, one or more emission filters, and / or one or more excitation filters.

[0318] When the Figure 16D tray 411, in which the microfluidic cartridge 200 is inserted as shown (but not shown in this figure), is in its docking position in the device, the microfluidic cartridge 200 is located below the sensor assembly 1620 and the illumination assembly 1610. The sensor assembly 1620 receives a signal from the diagnostic portion of the microfluidic cartridge, which is generated by irradiating a light beam on the diagnostic portion by the illumination assembly 1610. Then, the received signal is sent to a control unit (not shown) for analysis.

[0319] The sensor assembly 1620 may have a high quantum efficiency within its detection wavelength range. In an exemplary embodiment, the camera 1621 of the sensor assembly 430 may be a charge-coupled device (CCD) or any other suitable camera. In an exemplary embodiment, the camera 1621 is a near-infrared optimized camera with a 2 / 3 type (diagonal 11.0 mm) CCD sensor.

[0320] The camera lens 1622 of the sensor assembly 1620 may be a lens for any suitable camera 1621 or a higher-quality lens, such as a microscope-grade lens, depending on the type of immunoassay used. In an exemplary embodiment, since the analyte is physically small, the camera lens 1622 is responsible for assisting the camera 1621 in focusing on the analyte. In an exemplary embodiment, the camera lens 1622 is a C-mount lens. In some embodiments, the C-mount lens is located between the camera 1621 and the objective lens 1623. In some exemplary embodiments, the C-mount lens is firmly attached to the camera 1621. In an exemplary embodiment, the effective focal length of the C-mount lens is 20 - 30 mm.

[0321] In an exemplary embodiment, the optical unit 430 includes one or more filters 1613. The one or more filters 1613 can be used to filter any light with an unwanted wavelength generated from the light source and any unwanted noise in the signal picked up by the camera.

[0322] Depending on the light source 1611 and fluorophore used, one or more filters 1613 can be used. The illumination assembly 1610 is connected to the filter 1613. In an exemplary embodiment, the camera 1621 is connected to the camera lens 1622, and these two components are connected to one or more filters 1613. The one or more filters 1613 are mounted and aligned between the camera lens 1622 and the objective lens 1623. This connection with the one or more filters 1613 allows any unwanted signals (e.g., noise, which typically has a different wavelength and is generated by the biometric or any unwanted reaction) to be filtered, and thus minimizes the unwanted interference with the true signal. In an exemplary embodiment, the one or more filters 1613 are also connected to the light pipe 1612 at an angle, which helps to focus the filtered light beam onto the biometric. In another exemplary embodiment, the angle is 0 degrees. In yet another exemplary embodiment, the angle is between 1 degree and 50 degrees. In an exemplary embodiment, the one or more filters 1613 are a filter set containing one or more dichroic filters, one or more emission filters, and one or more excitation filters. In an exemplary embodiment, the filter set is configured to change the optical path such that when the microfluidic cartridge is positioned in the designated area, the light generated by the light source 1611 can be directed to irradiate the diagnostic portion of the microfluidic cartridge perpendicular to the axis of the cartridge chamber.

[0323] In an exemplary embodiment, a fluorescence filter set for CY5 fluorescein is used. In another exemplary embodiment, the fluorescence filter set for CY5 fluorescein has the following specifications shown:

[0324] Excitation band (nm): 600 - 650

[0325] Emission band (nm): 670 - 710

[0326] Dichroic reflection band (nm): 550 - 650

[0327] Cross - band (nm): 650 - 800

[0328] In some exemplary embodiments, the optical unit 430 provides a filtered light beam with a wavelength in the range of 400 nm to 700 nm. In another exemplary embodiment, the optical unit 430 provides a filtered light beam with a wavelength in the range of 600 nm to 650 nm.

[0329] In an exemplary embodiment, the objective lens 1623 of the sensor assembly 1620 is a plano-achromatic objective lens with a magnification of 4x, an effective focal length of 45 - 55 nm, and a coating covering wavelengths from UV to NIR.

[0330] Figure 17 Also shown is the identification unit 470 of the portable diagnostic device 400 as shown in Figure 14B . The identification unit 470 is configured to read the identification of a microfluidic cartridge (not shown in this figure) and transmit a corresponding identification signal to a control unit (not shown). In some exemplary embodiments, the identification unit 470 includes a reader 1632 that is configured to read the identification of the microfluidic cartridge. In some exemplary embodiments, the identification unit 470 is attached or fixed to the optical unit 430. In one exemplary embodiment as shown in Figure 17 , the identification unit 470 further includes a reader mount 1631 to accommodate the reader 1632 and attach the reader to the bracket of the optical unit 430. The reader 1632 is located directly above the designated area where the microfluidic cartridge will be placed and is pointed at the microfluidic cartridge.

[0331] In an exemplary embodiment, the reader 1632 is a barcode reader. The barcode reader can read a 2D barcode attached or fixed to the microfluidic cartridge. In an exemplary embodiment, the barcode is attached or fixed to the microfluidic cartridge (see Figure 11A ). In another exemplary embodiment, a two-dimensional (2D) code is attached or fixed to the microfluidic cartridge. The 2D code incorporating the identification of the microfluidic cartridge, the analyte or disease to be tested, and the expiration date of the chip is placed on the microfluidic cartridge during the manufacturing process. After the microfluidic cartridge is inserted into the tray, the barcode reader is activated, and the barcode reader automatically scans the 2D code. The software can automatically select the correct program to use based on the 2D code. This feature eliminates the need for manual selection of the pulse program, making the design more user-friendly and less prone to human error. In an exemplary embodiment, the software can also identify previously used or defective microfluidic cartridges. The software displays a warning message on the screen and does not continue with the program.

[0332] Now refer to Figure 18 , as shown in Figure 14BThe components in the optical unit 430, the identification unit 470, the micro-valve controller 421 of the cartridge driving unit 420, and the cartridge accommodating unit 410 of the portable diagnostic device 400 shown in [description] are arranged such that a compact integrated assembly 480 is formed. This compact design results in a smaller and lighter diagnostic system. The diagnostic system should be small and light enough to be movable between clinics when needed. In one exemplary embodiment, the present invention is small and light enough to be carried onto domestic flights. In one exemplary embodiment, the device has dimensions of approximately 30x30x30 cm 3 , and weighs approximately 5-6 kg.

[0333] Figure 18 The configuration and spatial relationship between the units integrated in the assembly 480 are shown. The spatial arrangement of the components in each unit has been described previously. In one exemplary embodiment, the camera 1621 and the camera lens 1622 mounted thereon are located in the second region 1524B of the track assembly near the opening 1524 (not shown in this figure, but in Figure 16AOn one side (shown in the figure) and axially aligned with this plane of the cartridge chamber. In this figure, it is shown at the top of the assembly 480. These two components are connected to one or more filters (not shown) mounted in the filter mount 1625. The filters are mounted and optically aligned between the camera lens 1622 and the objective lens 1623 positioned below the filter mount 1625. The light pipe 1612 of the illumination assembly 1610 is also attached to an opening on the side of the filter mount 1625 and optically aligned to illuminate on the same side as the camera lens of the track assembly 412 perpendicular to the axis of the cartridge chamber. When the light beam generated by the light source 1611 enters one or more filters, the one or more filters only allow light with a specific wavelength or wavelength range to pass through and reach the biometric and filter out light with unwanted wavelengths. In this embodiment, the track assembly 412 of the cartridge receiving unit 410 is located below the objective lens 1623 of the optical unit 430. In one embodiment, the optical unit 430 and the track assembly 412 are firmly mounted on two brackets 1627 located on opposite sides of the assembly 480 such that they are held together as an integral part of the device. Each bracket 1627 has a section extending from the bottom of the track assembly 412 to the camera 1621 and is shaped to fit the optical unit 430 and the cartridge receiving unit 410 to support the structure of the assembly 480 when all the components are assembled together. In an exemplary embodiment, the reader mount 1631 of the identification unit 470 on which the reader 1632 is mounted is attached to the bracket of the optical unit 430 by being mounted on the two brackets 1627 and aligned with the third region 1524C of the opening 1524. In this embodiment, the reader 1632 is located above the cartridge receiving unit 410 and points to the designated area where the microfluidic cartridge (not shown) will be placed to scan the code attached to the microfluidic cartridge.

[0334] In the present exemplary embodiment shown, the track assembly 412, the microfluidic cartridge drive unit 420, the optical unit 430, and the identification unit 470 of the cartridge receiving unit 410 are installed in a housing in a certain configuration such that when the microfluidic cartridge is inserted into the device, there is a space for receiving the microfluidic cartridge. In the present exemplary embodiment, when the microfluidic cartridge is inserted into the tray 411 and the tray 411 is slid to the docking position, the microfluidic cartridge is positioned in a designated area of the space. The space includes one or more microvalve positions and one or more micropump positions. As shown, the microvalve controller 421 is firmly mounted on the track assembly 412 and is positioned side by side with the microvalves of the microfluidic cartridge inserted into the space such that the heating elements of the microvalve controller 421 correspond to the positions of the microvalves. The illumination assembly 1610 and the sensor assembly 1620 are axially aligned with the plane of the cartridge chamber and are mounted to directly point at the diagnostic portion of the microfluidic cartridge. The opening 1524 ensures that the diagnostic portion of the microfluidic cartridge is directly below the camera lens 1623 of the optical unit 430 for inspection. The sensor assembly 1620 receives signals from the diagnostic portion of the microfluidic cartridge, which are generated by the illumination assembly 1610 radiating a light beam onto the diagnostic portion. In one embodiment, the received signals can be sent to a control unit (not shown) for analysis.

[0335] In some exemplary embodiments, the assembly 480 further includes a switch 1526 (not shown in this figure but shown in Figure 16B . In another exemplary embodiment, the switch 1526 is a microswitch. The microswitch can be attached to the back of the track assembly 412 and is electrically connected to a power supply unit (not shown). When the tray 411 with the microfluidic cartridge inserted therein is slid to the docking position through the track assembly 412, the microswitch is automatically activated. After activation, the microswitch can turn on the reader 1632 to read the identification of the microfluidic cartridge 200 and automatically select the program to be used.

[0336] The events associated with the assembly 480 of the device are described below:

[0337] S1. The user places the microfluidic cartridge into the cartridge chamber of the tray 411.

[0338] S2. The user pushes the tray 411 into the device under the guidance of the track assembly 412.

[0339] S3. When the tray 411 is pushed and fixed in the docking position, the switch 1526 is activated.

[0340] S4. The switch 1526 turns on the barcode reader 1632.

[0341] S5. The reader 1632 reads the code printed or attached to the microfluidic cartridge.

[0342] S6. The code contains an identification of the microfluidic cartridge, which prompts the software of the control unit to automatically select the program associated with this microfluidic cartridge.

[0343] S7. Once the software selects the correct program, the microvalve controller 421 and the micropump controller (not shown in this figure) cooperate to actuate the fluid to flow from the reservoir to the diagnostic section in a predetermined order.

[0344] S8. Once the reaction is completed in the diagnostic section, the illumination assembly 1610 is activated, and the analyte is excited by the light beam generated by the light source 1611.

[0345] S9. The sensor assembly 1620 captures an optical image and analyzes the image through software.

[0346] S10. The result is displayed on the screen for the user to view. No manual interpretation is required.

[0347] In one exemplary embodiment, the operation of the diagnostic device when the microfluidic cartridge is inserted therein is shown in Figure 19 and described in detail below:

[0348] Box 1810 indicates that by opening the microvalve that seals the reservoir of the microfluidic cartridge and actuating the micropump in the microfluidic cartridge, the sample and one or more reagents are guided from the microfluidic section to the diagnostic section in a predetermined order within the microfluidic cartridge.

[0349] In some exemplary embodiments, the predetermined order includes a step of dispensing the analyte. In the step of dispensing the analyte, the fluid (e.g., the sample, one or more buffers, and one or more reagents) exits the channel openings in sequence, thereby spreading across the diagnostic chamber, and these fluids are in direct contact with the diagnostic chip. The area where the sample, one or more buffers, and one or more reagents are dispensed covers the location where the detection point array is located, such that one or more analytes can interact / react with the analyte interaction molecules pre-coated on the detection points. In one exemplary embodiment, the step of dispensing the analyte may further include the following steps: further driving the microfluidic cartridge to spread a second auxiliary reagent located at one reservoir by flowing through the microchannel to reach the diagnostic section, thereby attaching a second molecule to facilitate the detection of the analyte in the reaction or interaction after the sample and reagents are spread on the detection point array. In yet another exemplary embodiment, the pre-coated analyte has been bound to a certain molecule, which is used to detect the analyte without the need for a second molecule. This molecule may be a molecule that can generate a fluorescence signal or other detection signals for subsequent analysis steps.

[0350] In an exemplary embodiment, the micro - pump controller of the cartridge drive unit generates a specific sequence of electrical pulses, and the sequence of electrical pulses passes through the microfluidic cartridge via an electrical connector located at the bottom of the tray. This sequence of electrical pulses can drive the micro - pump to facilitate the movement of fluid within the microfluidic cartridge. At the same time, the micro - valve controller receives a signal from the cartridge drive unit to apply thermal energy to a specific micro - valve location on the microfluidic cartridge, thereby opening the micro - valve. The micro - valve controller and the micro - pump controller operate in concert to drive the sample or reagent in the microfluidic cartridge out of its reservoir and push them into the diagnostic section in a predetermined order.

[0351] In an exemplary embodiment, the control unit of the device includes a microfluidic cartridge drive software module to control fluid actuation. The microfluidic cartridge drive software module is designed to instruct the cartridge drive unit to control the current and the time to transmit this current to the micro - pump of the microfluidic cartridge. The higher the current and / or the longer the time to transmit this current, the more fluid can then be pumped from the reservoir.

[0352] The microfluidic cartridge drive software module is also designed to instruct the cartridge drive unit to control the current and the time to transmit this current to the micro - valve controller, which controls the opening of the micro - valve by emitting thermal energy onto the surface of the micro - valve to cause the micro - valve to expand.

[0353] Block 1820 indicates that predetermined conditions are provided to the diagnostic section of the microfluidic cartridge to generate at least one signal.

[0354] In an exemplary embodiment, the predetermined conditions include an analysis step. The diagnostic section of the microfluidic cartridge is located below the optical sensor and is not separated from the microfluidic cartridge after the step of dispensing the analyte. After receiving a start signal from the control unit, a beam (e.g., a laser beam) from the illumination assembly of the optical unit is filtered and directed onto the diagnostic section to generate at least one signal (if the sample contains an analyte) that can be detected by the sensor assembly. In one embodiment, the at least one signal includes a fluorescence signal that is generated when the diagnostic section is irradiated with light of an appropriate wavelength. Block 1830 indicates that the at least one signal is detected and data is collected using the optical sensor.

[0355] In an exemplary embodiment, the signal (e.g., fluorescence signal) as described above is filtered by one or more filters of the optical unit and collected by the sensor assembly of the optical unit located above the diagnostic section. The one or more filters are used to filter out any unwanted noise in the signal picked up by the camera of the sensor assembly.

[0356] Block 1840 indicates that the data is analyzed to quantitatively and / or qualitatively determine the presence of the analyte.

[0357] In an exemplary embodiment, the collected signal will be converted into digital data, which will then be transferred to and analyzed by the microprocessor of the control unit to quantitatively or qualitatively determine the presence of the analyte. In an exemplary embodiment, the result will be displayed on the display unit of the device within a relatively short period of time. The overall process time (i.e., from inserting the microfluidic cartridge into the device to displaying the result) is only 10 - 25 minutes. In yet another exemplary embodiment, the overall process time is only about 15 minutes.

[0358] In an exemplary embodiment, the present invention has been designed to have minimal human intervention, which minimizes the possibility of human error. After all the reagents are pre-loaded into the microfluidic cartridge and sealed, only the sample chamber inlet is exposed and is the only obvious inlet where the sample should be loaded. This design minimizes the possibility that the user will load the sample into the wrong chamber. When the microfluidic cartridge is inserted into the device, the barcode reader scans the data matrix on the microfluidic cartridge and either rejects the cartridge (if it has already been used) or accepts the microfluidic cartridge and automatically selects the correct test program. This feature prevents any used microfluidic cartridge from being accidentally reused and prevents the user from making mistakes when selecting the test program on the diagnostic platform. The software embedded in the diagnostic platform analyzes the test results and displays them on the screen, which eliminates any possibility of human misinterpretation when reading the results.

[0359] Example 10

[0360] Device with intelligent functions

[0361] Now refer to Figure 20 , on the one hand, a portable diagnostic device 2010 is provided, which further includes a detachable intelligent device 2012 that is optionally connected and communicates with the portable diagnostic device 2010 to obtain prevalence information at a certain location (as Figure 10B shown in), wherein the intelligent device 2012 includes

[0362] an environmental measurement module 2013 for obtaining environmental data, where the environmental data includes at least one environmental parameter at the location;

[0363] a data storage module 2016 for storing raw data, where the raw data includes one or more of environmental data and diagnostic data;

[0364] a transmitter 2015 for transmitting the raw data to a remote server; and

[0365] a battery 2014.

[0366] The portable diagnostic device 2010 can be used to collect different types of diagnostic data. The diagnostic data can include disease type, disease severity, viral load, presence or absence of pathogens or allergens, or blood cell count. Examples of diagnostic data include, but are not limited to, data associated with the following: (1) animal diseases, such as porcine reproductive and respiratory syndrome (PRRS), foot-and-mouth disease (FMD) in cattle, classical swine fever (CSFV) infection, and bovine spongiform encephalopathy (BSE) infectious diseases, (2) food safety (e.g., detection of food allergens (e.g., peanuts, seafood), aflatoxin, and melamine), and (3) human diseases, such as infectious diseases (e.g., sexually transmitted diseases (STD), Middle East respiratory syndrome coronavirus (MERS-CoV), and influenza virus infection), tropical diseases (e.g., dengue virus and Japanese encephalitis virus infection), and emerging infectious diseases belonging to the antigen / antibody immune mechanism in their pathological pathways), influenza A, influenza B, RSV, HPIV, adenovirus, dengue, chikungunya, Zika, malaria, leptospirosis, toxoplasmosis, canine distemper virus Ab, canine parvovirus Ab, or heartworm.

[0367] In other embodiments, the portable diagnostic device 2010 can measure device data, where the device data is machine information or an operating state. In some embodiments, the machine information is selected from the group consisting of model number, machine identification, machine, hardware version, software version, original country of purchase, and owner. In other embodiments, the operating state is selected from the group consisting of error code, system voltage, total operating hours, and total number of tests.

[0368] According to another embodiment, the smart device 2012 includes an environmental measurement module 2013 for obtaining environmental data, where the environmental data includes at least one environmental parameter at the location. In some embodiments, the environmental data is selected from location data, humidity, temperature, atmospheric pressure, time, and air quality (AQI, pollen count, etc.). In some embodiments, the location data is a global location and is obtained by global positioning satellites (GPS). In some embodiments, the environmental data is selected from location data, humidity, temperature, and time.

[0369] In some embodiments, the environmental measurement module 2013, the transmitter 2015, and the data storage module 2016 together form the smart device 2012, which can optionally be connected to and communicate with the portable diagnostic device 2010 and the remote server 2020. In some embodiments, the smart device 2012 is detachable. The smart device 2012 can be of any size, but in certain embodiments, it is smaller than the device and can be assembled inside the device. In some embodiments, the detachable smart device can be placed in a housing.

[0370] According to other embodiments, the smart device 2012 further includes a battery 2014. In some embodiments, the battery is rechargeable and can operate for 30 days without being charged. In other embodiments, the transmitter 2015 is a wireless transmitter.

[0371] Still referring to Figure 20 , another aspect of the present invention provides a system 2040 for managing a network of portable diagnostic devices 2010 and obtaining prevalence information, where these portable diagnostic devices are each connected to and communicate with a detachable smart device 2012. The system includes at least one user terminal 2030 and a server 2020 including a data module 2021 for collecting and storing raw data, where the raw data includes one or more of the following:

[0372] Diagnostic data obtained using the portable diagnostic device 2010 at a certain location, where the diagnostic data includes at least one biochemical or pathological measurement of a subject,

[0373] Environmental data,

[0374] Device data obtained from the portable diagnostic device 2010, and

[0375] A data module for analyzing the raw data

[0376] where the server 2020 is connected to the user terminal 2030 and the detachable smart device 2012.

[0377] In some embodiments, environmental data is obtained at the location using the environmental measurement module 2013, where the environmental data includes at least one environmental parameter. In other embodiments, the environmental data is obtained from a third-party source, such as from an environmental measurement device or from a public record about the environment at the location (e.g., local news source, weather station report, or the Internet). Examples of environmental measurement devices include, but are not limited to, devices for measuring one or more of humidity, temperature, air velocity, air pressure, light, dust, sound, and vibration.

[0378] In some embodiments, the system 2040 includes a plurality of portable diagnostic devices 2010. In some embodiments, the system 2040 includes at least 2, 5, 10, 100, 1000, 10,000 portable diagnostic devices 2010. In some embodiments, the system includes 2 - 50, 10 - 100, 50 - 500, or 100 - 1000 portable diagnostic devices 2010.

[0379] In some aspects, server 2020 is a cloud-based platform. In certain embodiments, server 2020 is wirelessly connected to user terminal 2030 and portable diagnostic device 2010. In some embodiments, server 2020 further includes a software update module (not shown) to transfer software to portable diagnostic device 2010. This can include software containing diagnostic test protocol updates, firmware updates, and other types of software updates. In some aspects, server 2020 can send solutions to problems faced by the user in the form of remote technical support. For example, if the machine operation data or environmental data received by server 2020 indicates that there are certain problems with the device, server 2020 can send information or actual software updates to solve these problems.

[0380] According to another embodiment, data module 2022 for analyzing raw data performs one or more of the following steps:

[0381] Collect raw data;

[0382] Analyze the raw data to provide results; and transmit the results to user terminal 2030.

[0383] In some embodiments, data module 2022 is located on server 2020. In other embodiments, data analysis can be performed on another server, computer, or in a separate system.

[0384] In some embodiments, the analysis can be the creation of a database, statistical analysis, analyzing raw data (such as machine operation data or environmental data) to determine the cause of machine errors, creation of a mathematical model, analysis of current trends, correlation data, and mapping the prevalence to a specific location.

[0385] According to another embodiment, the data module provides one or more of the following results:

[0386] The prevalence at different locations shown on a map;

[0387] The prevalence over a period of time;

[0388] The severity of the disease in a specific location;

[0389] Remote technical support; and

[0390] Remote software updates.

[0391] Additionally, a correlation between environmental conditions and device status can be determined. For example, it can be analyzed whether one or more error codes occur due to the device being exposed to abnormal environmental temperatures (e.g., high heat) or humidity levels (high humidity) (measured by the environmental measurement module 2013). In another exemplary embodiment, other types of analysis can be performed on the data, including but not limited to the correlation between environmental conditions and disease outbreaks, disease associations, trends, patterns, prevalence, and migration.

[0392] According to another embodiment, the data module 2021 further includes one or more access controls for the raw data and results. In some embodiments, the access control is selected from a password or security code, where different levels of security can be implemented. Other types of access controls known to those skilled in the art can be used, including but not limited to incorporating the access control into another physical device (e.g., a mobile device) and using technologies (e.g., passwords, facial recognition, fingerprint identification, two-factor authentication, numeric keypads, or physical keys) to incorporate the access control therein. In some embodiments, the portable diagnostic device 2010 transmits the raw data to the server 2020 once per hour. In some embodiments, when the portable diagnostic device 2010 is not connected to an external power source, the portable diagnostic device 2010 transmits the raw data to the server 2020.

[0393] According to another embodiment, the system 2040 includes at least one user terminal 2030 or user interface (not shown). In some embodiments, the user terminal 2030 or interface is a computer or a mobile device. In some embodiments, the mobile device has wireless network capabilities and is wirelessly connected to the server. In some embodiments, wireless communication is performed through one or more of the following wireless technologies, including but not limited to satellite, Bluetooth, radio, Wi-Fi, wireless broadband, or cellular (e.g., 2G, 3G, 4G, 5G). In some embodiments, the mobile device further includes an interface for displaying the results of the data module (e.g., a mobile application).

[0394] According to another embodiment, the system 2040 includes multiple portable diagnostic devices 2010, multiple user terminals 2030, and at least one server 2020.

[0395] Another aspect of the present invention provides a method for obtaining prevalence information at a certain location as shown in Figure 21 and is described in detail below:

[0396] Block 2110 indicates that diagnostic data or samples are obtained at the location using a portable diagnostic device, where the diagnostic data includes at least one biochemical or pathological measurement of the subject.

[0397] Block 2120 indicates that environmental data is obtained.

[0398] Box 2130 indicates that diagnostic data and environmental data are transmitted to the server.

[0399] Box 2140 indicates that in the server, diagnostic data and environmental data of multiple subjects in multiple locations are collected and stored to form a database.

[0400] Box 2150 indicates that the prevalence or environmental information of the subjects or locations in the database is analyzed.

[0401] Some embodiments further include one or more of the following steps as shown in Figure 22 and are described in detail below:

[0402] Box 2210 indicates that the raw data at the location is obtained and stored on the data storage module.

[0403] Box 2220 indicates that the raw data is transmitted from the data storage module to the server.

[0404] Box 2230 indicates that in the server, multiple raw data from multiple subjects in multiple locations are collected and stored to form a database.

[0405] Box 2240 indicates that the database is analyzed to provide results, where the results provide prevalence information.

[0406] The raw data includes one or more of the following:

[0407] Diagnostic data obtained at a location using a portable diagnostic device, where the diagnostic data includes at least one biochemical or pathological measurement of the subject.

[0408] Environmental data.

[0409] Device data obtained from the device.

[0410] In some embodiments, the portable diagnostic device is the device described herein. In some embodiments, environmental data is obtained at the location using an environmental measurement module, where the environmental data includes at least one environmental parameter. In other embodiments, the environmental data is obtained from a third-party source, such as from an environmental measurement device or from public information about the environment at the location (e.g., local news sources, weather station reports, or the Internet). Examples of environmental measurement devices include, but are not limited to, devices for measuring one or more of humidity, temperature, air velocity, air pressure, light, dust, sound, and vibration. In some embodiments, the environmental measurement device includes a device for measuring location data, such as GPS (Global Positioning System).

[0411] In some embodiments, the system authorizes users to access the raw data, databases, and results based on access rights.

[0412] Some embodiments further include the step of transferring software from the server to the device. In some embodiments, the raw data is transferred to the server once an hour even when the device is not connected to an external power source.

[0413] Figure 23 is a flowchart showing information and data flows of the various components of a system according to an embodiment of the present invention. The system includes a portable diagnostic device 2010, a smart device 2012, a server 2020, and one or more system users who interact with the system via a user interface or terminal.

[0414] The portable diagnostic device 2010 records raw data (e.g., machine identification, operating status, and diagnostic data) and sends the raw data to the smart device 2012. The smart device 2012 receives the raw data, records environmental data, and transfers the raw data and environmental data to the server 2020.

[0415] The server 2020 receives and stores the raw data and environmental data received from the smart device 2012. If the portable diagnostic device 2010 is connected to the network, the server 2020 can also directly receive and store the raw data from the portable diagnostic device 2010. The server 2020 sends updated software to the portable diagnostic device 2010 via the network or via the smart device 2012. The server 2020 sends the updated software directly to the smart device 2012 without using a separate network (e.g., Wi-Fi or cellular connection). The server 2020 controls access to data and statistical information according to the user's access rights.

[0416] The server 2020 also analyzes data from the smart device 2012, the portable diagnostic device 2010, and even third-party sources for data analysis and creates results such as statistical information, prevalence analysis, disease trends, and other reports.

[0417] Different types of users can access the server 2020. The superuser 2304 has full control and can manage software updates for multiple devices and smart devices. It can also control the access rights of individual users to the server 2020. Individual users 2305 can access data and results according to their individual user permissions.

[0418] Figure 24Schematic diagram of the combination of the intelligent device 2012 and the units interacting therewith (i.e., the portable diagnostic device 2010 and the server 2020). The intelligent device 2012 includes a processor 2401, a data storage module 2408, a humidity sensor 2402, a temperature sensor 2403, a GPS 2404, a connection port 2405, a connection port 2406, and a wireless module 2407.

[0419] The processor 2401 is connected to the data storage module 2408, the humidity sensor 2402, the temperature sensor 2403, the GPS 2404, the connection port 2405, and the wireless module 2407. The processor 2401 collects data from the humidity sensor 2402, the temperature sensor 2403, and the GPS 2404, and also collects raw data and machine data from the portable diagnostic device 2010 via the connection port 2405. The data collected by the processor 2401 is stored in the data storage module 2408. The processor 2401 can directly send the data to the server 2020 via the wireless module 2407 for further analysis. The wireless module 2407 consists of a Wi-Fi module and a cellular module (e.g., 4G). In another exemplary embodiment, the processor 2401 can also analyze all the data.

[0420] The battery 2409 is connected to the processor 2401 via the connection port 2406, and provides power to operate the processor 2401 and enable wireless data transmission to the server 2020.

[0421] Therefore, the exemplary embodiments of the present invention are fully described. Although the description relates to specific embodiments, it will be clear to those skilled in the art that the present invention can be practiced by changing these specific details. Therefore, the present invention should not be construed as limited to the embodiments set forth herein.

[0422] For example, the device can further include at least one USB port or any other data communication device to allow the operation of a general data transfer communication protocol. A display unit is provided in the device for the human-machine interface. The display unit 450 is a high-resolution color display, which can be a liquid crystal display (LCD), an organic light-emitting diode (OLED), or other types of displays. The display unit can be combined with a touch screen panel; thus, it can receive commands from the touch of a human finger. The display unit is optionally connected to the control unit 440. However, the way it displays the displayed content is through a graphical user interface.

[0423] Exemplary microfluidic chips that can be used can be the microfluidic chips disclosed in German Patent Application Nos. DE102010061910.8, DE102010061909.4, DE102014117976A1, and DE502007004366.4.

[0424] In yet another alternative embodiment, instead of using at least one light beam, at least one laser beam may be used to generate at least one signal for analysis. In this alternative embodiment, the illumination assembly 1610 emits at least one laser beam having at least one predetermined wavelength onto the diagnostic section 210. The illumination assembly 1610 includes a diode laser, at least one filter, and at least one dichroic mirror.

[0425] In another embodiment, the illumination assembly 1610 may have more than one diode laser or more than one LED.

[0426] In yet another embodiment, the camera 1621 of the optical unit 430 may be a digital high-resolution camera, wherein the sensor is selected from the group consisting of: a complementary metal oxide semiconductor (CMOS) sensor and a charge-coupled device (CCD) sensor. The number of megapixels of the image sensor of the digital high-resolution camera is in the range of 1.0 megapixel to 30 megapixels.

[0427] In yet another embodiment, the portable diagnostic device 400 may include a plurality of cassette drive units 420, a plurality of cassette receiving units 410, and a plurality of optical units 430 such that a plurality of analyses / diagnoses may be run simultaneously. Although we have described multiple embodiments of the present invention, it should be understood that these examples may be varied to provide other embodiments of the present invention. Accordingly, the scope of the present invention should be defined by the following claims rather than by the specific embodiments provided herein.

Claims

1. A portable diagnostic device for detecting at least one analyte from a sample using a microfluidic cartridge, the microfluidic cartridge having a plurality of micropumps, a plurality of reservoirs connected to at least one diagnostic section via microchannels, and a plurality of microvalves for sealing the fluid in the reservoirs from flowing into the reaction site, the portable diagnostic device comprising a cartridge receiving unit, a cartridge driver unit, and an optical unit, The cartridge receiving unit is configured to receive the microfluidic cartridge; The cartridge driver unit includes a) a microvalve controller configured to control the microvalves; wherein the microvalve controller includes at least one heating element configured to apply thermal energy to a thermally deformable surface of at least one of the plurality of microvalves to open the microvalve, wherein the heating element is an infrared emitter, and b) a micropump controller configured to actuate the micropumps, wherein the micropump controller and the microvalve controller are configured to actuate the fluid to flow from the reservoirs to the diagnostic section in a predetermined order; And When the microfluidic cartridge is placed in the cartridge receiving unit, the optical unit is aligned with the diagnostic section.

2. The portable diagnostic device according to claim 1, wherein when the cartridge is placed in the cartridge receiving unit, the at least one heating element is juxtaposed with at least one microvalve of the microfluidic cartridge.

3. The portable diagnostic device according to claim 1, wherein the micropump controller includes at least one electrical connector for electrically connecting to the at least one micropump of the microfluidic cartridge, and the at least one electrical connector is configured to supply current to the at least one micropump.

4. The portable diagnostic device according to claim 1, wherein The optical unit includes an illumination assembly and a sensor assembly, wherein a. The illumination assembly is configured to transmit light to the diagnostic section of the microfluidic cartridge, and b. The sensor assembly is configured to detect at least one signal generated by the diagnostic section due to the presence of the analyte when the microfluidic cartridge is inserted and operated under predetermined conditions.

5. The portable diagnostic device according to claim 4, wherein the illumination assembly includes a light source having a wavelength in the range of 600 nm to 650 nm, and the at least one data signal is a fluorescence signal.

6. The portable diagnostic device according to claim 1, further comprising a control unit configured to perform one or more of the following: a. Provide a predetermined control sequence to the cartridge driver unit to direct the movement of at least one fluid within the microfluidic cartridge; b. Provide predetermined conditions to the optical unit to perform quantitative and / or qualitative analysis of the analyte; c. Store the data signals obtained from the optical unit; And d. Control and monitor the operation of the device.

7. The portable diagnostic device according to claim 6, wherein the control unit is configured to provide a predetermined sequence to the cartridge driver unit and predetermined conditions to the optical unit according to the identification of the microfluidic cartridge.

8. The portable diagnostic device according to claim 1, further comprising a housing for anchoring the cartridge receiving unit, the cartridge driving unit, and the optical unit therein wherein, the cartridge receiving unit further comprises a rail assembly and a tray, wherein the rail assembly comprises a pair of slidable rails, the tray is configured to receive the microfluidic cartridge and is anchored on the pair of rails, wherein the rails enable the tray to slide into and out of the housing such that the microfluidic cartridge can be inserted into the housing.

9. The portable diagnostic device according to claim 8, wherein the rail assembly of the cartridge receiving unit, the cartridge driving unit, and the optical unit are mounted in the housing in a configuration such that when the microfluidic cartridge is inserted into the portable diagnostic device, there is a space for receiving the microfluidic cartridge, the space including one or more microvalve positions, one or more micropump positions, and reaction positions corresponding respectively to the positions of the one or more microvalves, the one or more micropumps, and the reaction sites when the microfluidic cartridge is inserted into the space; the heating element of the microvalve controller is mounted near the microvalve position, wherein when the microfluidic cartridge is inserted, heat can be directed to the microvalve on the microfluidic cartridge; and the one or more electrical connectors of the micropump controller are mounted side by side with the one or more micropumps to be electrically connected to the at least one micropump when the microfluidic cartridge is inserted into the portable diagnostic device.

10. The portable diagnostic device according to claim 1, wherein the optical unit comprises an illumination assembly, the illumination assembly comprising a light source and a sensor assembly, the sensor assembly comprising a light sensor, wherein the light source and the light sensor are mounted to point at the diagnostic portion of the microfluidic cartridge.

11. The portable diagnostic device according to claim 1, further comprising a built-in or removable rechargeable battery.

12. The portable diagnostic device according to claim 6, further comprising an identification unit for reading the identification of the microfluidic cartridge and transmitting a corresponding identification signal to the control unit.

13. The portable diagnostic device according to claim 12, further comprising a switch for triggering the identification unit to read the identification of the microfluidic cartridge when the microfluidic cartridge is positioned in a designated area.

14. The portable diagnostic device according to claim 1, wherein the portable diagnostic device does not include any means for actuating fluids outside the microfluidic cartridge, and wherein the portable diagnostic device does not provide any reagents.

15. The portable diagnostic device according to claim 6, further comprising a user interface unit configured to display the quantitative and / or qualitative analysis of the analyte, wherein the user interface unit is connected to the control unit.

16. The portable diagnostic device according to claim 1, wherein The cartridge receiving unit and the cartridge drive unit are configured to connect to the microfluidic cartridge when the microfluidic cartridge is fixed at a designated area; The cartridge receiving unit receives and fixes the microfluidic cartridge at the designated area; The micro-valve controller is arranged side by side with at least one micro-valve; and The micro-pump controller is electrically connected to at least one micro-pump; Thereby, fluid actuation and analyte detection are performed within the designated area during operation.

17. The portable diagnostic device according to claim 16, wherein the cartridge receiving unit includes a rail assembly and a tray, wherein The rail assembly includes a cavity for slidably receiving the tray, The tray includes a cartridge chamber for receiving the microfluidic cartridge such that the microfluidic cartridge is positioned at the designated area.

18. The portable diagnostic device according to claim 1, further comprising a detachable device, wherein the detachable device includes a. An environmental measurement module for acquiring environmental data at a certain location, wherein the environmental data includes at least one environmental parameter at the location; b. A data storage module for storing raw data, wherein the raw data includes one or more of environmental data and diagnostic data; and c. A transmitter for transmitting the raw data to a remote server.

19. The portable diagnostic device according to claim 18, wherein the environmental data is selected from location data, humidity, temperature, and time.

20. The portable diagnostic device according to claim 18, wherein the detachable device can optionally be connected to and communicate with the portable diagnostic device and the remote server.

21. The portable diagnostic device according to claim 18, wherein the detachable device further includes a battery, wherein the battery is rechargeable and capable of operating for 30 days without charging.

22. A method for detecting at least one analyte from a sample using the portable diagnostic device according to claim 1, wherein the method comprises the following steps: a) Loading the sample into the microfluidic cartridge; b) Guiding the sample and at least one reagent from the microfluidic section to the diagnostic section within the microfluidic cartridge in a predetermined order by opening at least one micro-valve sealing at least one reservoir of the microfluidic cartridge and actuating at least one micro-pump in the microfluidic cartridge; c) Providing predetermined conditions to the diagnostic section of the microfluidic cartridge to generate at least one signal; d) Detecting the at least one data signal using an optical sensor and collecting diagnostic data; and e) Analyzing the diagnostic data to quantitatively and / or qualitatively determine the presence of the analyte.

23. The method according to claim 22, further comprising the following steps: a) Reading the identification of the microfluidic cartridge; b) Providing a predetermined order to the cartridge drive unit based on the identification of the microfluidic cartridge and providing predetermined conditions to the optical unit.

24. A method for obtaining prevalence information, which includes a. Obtain diagnostic data or a sample at a location using the portable diagnostic device according to claim 18, wherein the diagnostic data includes at least one biochemical or pathological measurement of a subject; b. Obtain environmental data at the location; c. Transmit the diagnostic data and the environmental data to a server; d. In the server, collect and store the diagnostic data and the environmental data of multiple subjects at multiple locations to form a database; and e. Analyze the prevalence information of the subjects at the multiple locations in the database.

25. A system for managing a network of portable diagnostic devices, comprising at least one portable diagnostic device according to claim 18, at least one user terminal, and a server, which includes a data module for collecting and storing raw data, wherein the raw data includes one or more of the following: (a) Diagnostic data obtained at a location using a portable diagnostic device, wherein the diagnostic data includes at least one biochemical or pathological measurement of a subject, (b) Environmental data obtained at the location using an environmental measurement module, wherein the environmental data includes at least one environmental parameter, (c) Device data obtained from the portable diagnostic device, and (d) A data module for analyzing the raw data wherein the server is configured to communicate with the user terminal and the portable diagnostic device.

26. The system according to claim 25, which includes a plurality of portable diagnostic devices, wherein the server is a cloud-based platform wirelessly connected to the user terminal and the portable diagnostic device.

27. The system according to claim 25, wherein the data module is configured to perform one or more of the following steps:

1. Collect raw data; 2. Analyze the raw data to provide results ； and 3. Transmit the results to the user terminal; and provide one or more of the following results:

1. Prevalence at different locations displayed on a map; 2. Prevalence over a period of time; 3. Severity of a disease in a specific location; and 4. Correlation between environmental conditions and device status.

28. The system according to claim 27, wherein the data module further includes one or more access controls for the raw data and the results.

29. A method of using the system according to claim 25, which includes the following steps: i. Obtain the raw data at the location and store it on a data storage module; ii. Transmit the raw data from the data storage module to the server; iii. In the server, collect and store multiple raw data from multiple portable diagnostic devices to form a database; iv. Analyze the database to provide results; wherein the raw data includes one or more of the following: i. Diagnostic data obtained at a location using a portable diagnostic device, wherein the diagnostic data includes at least one biochemical or pathological measurement of a subject; ii. Environmental data obtained by the environmental measurement module at the location, where the environmental data includes at least one environmental parameter; iii. Device data obtained from the portable diagnostic device.

30. The method according to claim 29, wherein the raw data is transmitted to the server once per hour even when the portable diagnostic device is not connected to an external power source.

31. The method according to claim 29, wherein the raw data is diagnostic data obtained using a portable diagnostic device at a certain location, where the diagnostic data includes at least one biochemical or pathological measurement value of a subject and location data; and the result provides prevalence information.

32. The method according to claim 29, wherein the raw data is one or more of temperature, humidity, time, location data, and device data; and the result provides information associated with the performance of the portable diagnostic device.

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