RU2817814C2 - Microfluidic device for blood sample preparation for analysis - Google Patents

Abstract

FIELD: medical equipment.

SUBSTANCE: microfluidic device for preparing a blood sample for analysis comprises a substrate including opposite first and second sides; a chamber extending into the substrate from the first side to the second side to the base. Chamber comprises protruding elements forming a wall of the chamber; and a main channel extending along at least a portion of the chamber wall along the chamber base. Chamber has a conical shape so that the chamber narrows inward from the first side to the second side, the projecting elements include overlapping plates forming the chamber wall. Main channel is located between the plates forming the wall and the base.

EFFECT: preventing the spread of infections.

8 cl, 8 dwg

Description

CROSS REFERENCE

This application is a continuation in part of a joint patent application under the Patent Cooperation Treaty (PCT) No. PCT/IL2018/050132, filed February 6, 2018, entitled: "Portable Digital Diagnostic Device", which is related to and claims priority under the provisional application US Co-Patent No. 62/454,933, entitled: "Portable Digital Diagnostic Device", filed February 6, 2017, the contents of each of the aforementioned patent applications being incorporated herein by reference in their entirety.

TECHNICAL FIELD

The present invention relates to a portable device for on-site diagnosis of diseases.

BACKGROUND OF THE ART

Many clinical studies require a blood sample to be taken to make a diagnosis. Currently, the collection of a patient's blood sample is done on site or at a third party. Next, the patient must wait for the test results as the blood sample must be taken to a laboratory for analysis, usually through microscopy performed by trained staff. However, the collection of the blood sample itself should be carried out by trained personnel using syringes, butterfly needles, blood tubes and other blood collection devices. Blood collection devices must be stored in accordance with established standards and hygiene requirements to avoid contamination and, therefore, unfitness for use. In addition, after the blood sample is delivered to the microscopist, the sample must be “smeared” for later use in microscopy or other analysis.

Microscopy is the gold standard for laboratory testing. In more than 50% of the world's countries, clinics with microscopic equipment are rare, as are trained microscopists who can set up microscopic equipment and make a diagnosis from a blood or tissue sample. In addition, obtaining an analysis result using microscopy takes a long time and is certainly not a quick process, regardless of the characteristics of the microscope and whether microscopists are located on site, in a medical clinic, hospital or other facilities. Additionally, in many parts of the world, trained microscopists and laboratories with suitable microscopy equipment are limited in number and may be located at a distance from various populations, such as village residents, which poses additional challenges to blood microscopy testing.

There are also challenges associated with transporting a blood sample to a microscopy laboratory due to possible improper handling of the sample, as well as possible sample deterioration due to weather and transport time from the patient to the laboratory. These blood tests are also expensive and, as a result, are unaffordable for many people. Moreover, because the result is not immediate and is typically obtained externally, it may not be possible to enter patient clinical data into the chart, and it may be difficult to provide timely feedback to infected patients who require immediate treatment.

Rapid diagnostic tests (RDTs) provide instant results. However, RDTs are not available for the diagnosis of many diseases, and disease detection is characterized by insignificant accuracy required for early detection and, as a rule, has low clinical specificity. To ensure the accuracy and reliability of the results, it is necessary to ensure proper storage and handling of such RDTs. In addition, there are many manufacturers of BDT, and the quality of BDT varies greatly from manufacturer to manufacturer.

Because diseases spread quickly, it is important to diagnose them early and early. This will ensure timely treatment of patients in order to maintain their health, as well as prevent the spread of the disease. In many countries around the world, this is simply not possible due to a lack of laboratory facilities and trained specialists capable of making accurate diagnoses of diseases.

In addition, for some diseases, such as malaria, additional tests, such as the glucose-6-phosphate dehydrogenase deficiency (G6PD) test, are needed to select the safest and most appropriate treatment (based on WHO malaria elimination guidelines). Typically, this test, in addition to diagnosing malaria, is not available in many rural and remote areas of the world.

SUMMARY OF THE INVENTION

The present invention provides computerized devices that perform microscopic and electrochemical examinations in the field to perform on-site tests with instant results, eg in real time. The devices can be used by operators with minimal training, such as health care workers, nurses, technicians, and not just doctors.

The computerized devices are portable devices that can be transported to remote areas, giving millions of people access to health care they previously did not have. Instant results eliminate the need for unnecessary use (unnecessary administration) of medications, such as unnecessary antibiotics and/or antimalarials, as diseases and conditions are accurately diagnosed on the spot. In addition, by instantly identifying diseases and conditions, treatment protocols can be started immediately, eliminating the possibility of the spread of infectious and fatal diseases and conditions.

The computerized device is a dual-channel device, with one channel for imaging or microscopy (optical) and the other channel for electrochemistry (signals). Based on the results of these two channels, a diagnosis can be made that is more accurate and efficient than the results provided by existing devices in the field. This allows for rapid and safe treatment and follow-up of the disease, preventing its spread, and also allows for the creation of a patient record in real time for subsequent tracking of the disease and other data for timely and effective intervention by health authorities, research and other activities . The devices are, for example, a laboratory computerized platform that is programmed for various medical diagnostic applications based on the same RevDx hardware platform.

The described devices allow the user or medical personnel of any level of training to obtain a blood sample from a finger prick without the need for the presence of specially trained medical personnel. The devices described are designed to connect to a mobile device or laptop computer, such as a smartphone, with devices designed to analyze a blood sample and provide an instant diagnosis on site and in real time. Each of the devices performs its analysis using techniques such as machine learning and other network connections such as telemedicine, where an image of a blood sample is transmitted over a network, such as the Internet, to trained medical personnel at remote locations.

Thanks to such a timely and accurate diagnosis, it is possible to begin treatment of the patient much earlier than under the standard procedure. This allows you to maintain the patient’s health, and in the case of an infectious disease, prevent its spread.

The present invention uses a disposable sample preparation kit based on microfluidic technologies and/or biosensor/electrochemical strips with associated readout and analysis systems to diagnose multiple or dual aspects of diseases, typically on-site. For example, in malaria, microfluidic chips that perform reading and analysis are able to identify the type of malaria parasite with high accuracy and specificity, allowing the diagnosis of malaria in the early stages when parasite density is low (compared to later stages of malaria). A biosensor strip and reader channel are used to detect G6PD deficiency. It is important to ensure that primaquine treatment used to treat Plasmodium vivax (the causative agent of tertian malaria) is administered safely. In addition, primaquine is used to prevent the transmission of other types of malaria parasites. The biosensor reader channel will also be used for glucose monitoring. Because malaria can cause hypoglycemia (dangerously low glucose levels), this will help determine which patients should go to hospital.

In addition, since the microfluidic chip and biosensor strip are disposable and allow you to obtain a blood sample during testing, the process itself is sanitary, since the disease is not transmitted to other patients, and there is no chance of blood imbalance. It is also possible to test large numbers of patients in a small amount of time, and this can be done by medical personnel with little or no medical training. In addition, microfluidic chips and biosensor strips require a small amount of blood, which can be used as blood films. For example, blood may be drawn from a finger prick by a user or other person with little or no medical training.

Also, the cost of the process is low since microfluidic chips and biosensor strips are inexpensive and the device used is a one-time purchase that can be used over and over again.

Embodiments of the present invention relate to a device for analyzing disease states. The device includes: an image forming channel configured to visually provide a sample; and a signal channel including a signal analyzer for analyzing received signals based on electrochemical reactions emitted by the electrode in response to the sample to determine the presence of a disease condition.

If necessary, the device may additionally include: an analytical module configured to scan a visual image of the sample and determine the presence of a disease state from the scanned image.

If necessary, the analytical module can be configured to determine, based on the scanned image, the presence of a disease condition, including: determination of glucose-6-phosphate dehydrogenase deficiency, determination of blood glucose levels, detection of malaria parasites, including P. falciparum, P. vivax, R. malaria. P. ovale, P. knowlesi, and stages of disease, complete blood count, detection of multiple parasites including relapsing fever and filariae, tuberculosis, Pap smear testing, urinalysis, and veterinary disease detection.

If necessary, the device may additionally include: an optomechanical system for magnifying and scanning a sample, an optomechanical system interfaced with an analytical module.

If necessary, the device may additionally include: a processor programmed to determine the course of treatment of the disease, a processor interfaced with an analytical module.

If necessary, the device may further include: a processor programmed to determine treatment for a disease, a processor interfaced with an analytical module and a signal analyzer.

If necessary, the imaging channel and the signal channel may be configured to obtain confirmation of the presence of a disease state in real time.

If necessary, the device may include a display interfaced with an imaging channel and a signal channel.

Optionally, the device may include one or more of the following components: 1) a display screen, 2) a display output configured to communicate with an image sensor of an external computing device to display graphic images on the display screen of the external computing device.

Optionally, the imaging channel may include a first end for receiving a sample and an opposing second end coupled to a display.

If necessary, the device may additionally include: an analog-to-digital signal converter (ADC) interfaced with a signal analyzer; and a signal reader for reading electrochemical signals (eg, analog signals) emitted by the electrode in response to the sample, wherein the signal reader is coupled to the ADC.

If desired, the signal analyzer may be configured to analyze signals to determine the presence of a disease state, including:

determination of glucose-6-phosphate dehydrogenase deficiency, determination of blood glucose levels, identification of malaria parasites, including P. falciparum, P. vivax, P. malaria, P. ovale, and disease stages, complete blood count, detection of multiple parasites, including relapsing fever and filaria, tuberculosis, Pap smear testing and veterinary disease detection.

Optionally, the device may further include: a processor programmed to transmit data to a display, resulting in a user interface (UI) to provide a graphical representation of data regarding the presence of a disease condition.

Optionally, the device may further include: a location module coupled to at least an imaging channel or a signal channel, wherein the location module is configured to display a location in real time based on the display of global positioning system (GPS) data; in order to identify a disease state.

If necessary, the device may further include: a first port for receiving a microfluidic chip holding a sample that is imaged in the imaging channel; and a second port for receiving an electrode holding the sample in the signal channel.

Optionally, the device may further include: a microfluidic chip for preparing a sample for reception at the first port.

If desired, the device may further include a biosensor strip including an electrode for generating an electrochemical response upon contact with the sample for reception at the second port.

If desired, the sample may include portions of the same sample, and the sample may include at least one of the following: blood, urine, and tissue.

If desired, the microfluidic chip may be configured to mix the sample with one or more coloring agents, enhancing agents, and extenders.

Embodiments of the invention relate to a method for analyzing, for example, automatically analyzing disease states. The method includes: directing a sample into an imaging channel of a device including a display for viewing; and directing the sample to a signal channel of a device including a signal analyzer that analyzes the received signals based on electrochemical responses emitted by an electrode responsive to the sample to determine the presence of a disease condition.

Optionally, the method may provide information about the disease state detected by the signal analyzer on a display.

Optionally, the method may ensure that the sample sent to the imaging channel and the sample sent to the signal channel include parts of the same sample, which may include at least one of the following: blood, urine and fabric.

Embodiments of the invention are directed to a microfluidic device, also known as a microfluidic chip or chip. The microfluidic device includes: a substrate including opposing first and second sides; a chamber extending into the substrate from the first side to the second side to a base, the chamber including projecting members forming a wall of the chamber; and a main channel extending along at least a portion of the chamber wall along the base of the chamber.

Optionally, the microfluidic device may further include: at least one channel extending from the main channel, wherein at least one channel is configured to align with the optics of the device in which the substrate is viewed.

If desired, the microfluidic device may be configured with a chamber having a conical shape, with the chamber tapering inward from the first side to the second side.

If desired, the microfluidic device may be configured with protruding elements including a plurality of overlapping plates forming a chamber wall.

If necessary, the microfluidic device can be made with plates made of flexible and elastic material.

If necessary, the microfluidic device can be configured with a main channel located between (above) the plates forming the wall and base.

If necessary, the microfluidic device can be configured with a main channel having a C-shape and corresponding to the shape of the periphery of the chamber wall.

If desired, the microfluidic device can be configured with a main channel comprising opposing top and bottom walls with an outer wall that is located between the top and bottom walls.

If desired, the microfluidic device can be configured with a main channel whose outer wall is substantially perpendicular to opposing top and bottom walls.

If desired, the microfluidic device can be configured with a main channel sized to promote capillary action to move fluid through the main channel.

Optionally, the microfluidic device design may include a first side that contains a surface, as well as a chamber that extends into the substrate from the surface.

Optionally, the microfluidic device design may include at least one channel extending from the main channel that interacts with the environment through an openable opening such that communication with the environment causes the at least one channel exiting from the main channel, is filled with liquid (fluid) from the main channel.

This document contains references to the following directions: top, bottom, top, bottom, internal, external and their derivatives. These directional references are provided by way of example only and are intended to explain the described invention in terms of orientations that are illustrative only and not limiting in any way.

Unless otherwise specified, all technical and/or scientific terms used herein have the same meaning commonly assigned to them by those skilled in the art to which the invention relates. Although methods and materials similar or equivalent to those described herein may be used in the practice or testing of embodiments of the invention, examples of methods and/or materials are described below. In the event of a conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are for illustrative purposes only and are not intended to be strictly limiting.

BRIEF DESCRIPTION OF GRAPHIC MATERIALS

Certain embodiments of the invention are given herein by way of example only, with reference to the accompanying drawings, wherein like reference numerals or symbols represent corresponding or similar elements. Thus, when considering the figures, it is important to remember that the data shown is provided by way of example and for purposes of illustrative explanation of embodiments of the invention. In this regard, the description together with the figures allows those skilled in the art to understand how exactly the embodiments of the invention can be implemented.

Attention should now be directed to the figures wherein like reference numerals or symbols refer to corresponding or similar components. The figures look like this.

FIG. 1 is a diagram depicting a possible environment in which embodiments of the invention are carried out;

FIG. 2 is a block diagram of a base and computer device when used in combination, showing how these devices are associated with networks;

FIG. 3 is a schematic diagram of a base and computer device when used in combination;

FIG. 4A is a flow diagram showing an example process of the microscopic aspect of the present invention;

FIG. 4B is a flow diagram showing an example process of the electrochemical aspect of the present invention;

FIG. 5A is a block diagram of a stand-alone computing device in accordance with embodiments of the invention;

FIG. 5B is a block diagram of another stand-alone computing device in accordance with embodiments of the invention;

FIG. 5C is a perspective view of the device of FIG. 5V;

FIG. 6A-6D are microfluidic device illustrations for the described devices;

FIG. 6E-1A and 6E-1B are perspective top views of the microfluidic device for the described devices;

FIG. 6E-2 is a bottom view of the microfluidic device for the described devices;

FIG. 6E-3 is a cross-sectional view along line 6aa-6aa of the microfluidic device of FIG. 6E-1B;

FIG. 6E-4 is a cross-sectional view along line 6xx-6xx of the microfluidic device of FIG. 6E-1B, together with detailed sections;

FIG. 6E-5 is a cross-sectional view along line 6yy-6yy of the microfluidic device of FIG. 6E-1B, together with detailed sections;

FIG. 6E-6 is a photograph of the microfluidic device of FIG. 6E-1A, from the bottom or second side;

FIG. 6F is a top view of a microfluidic device for the described devices;

FIG. 6G is a top view of a circular microfluidic device for the described devices;

FIG. 7 is a flow diagram of the process performed by the described devices to detect malaria and, if detected, issue a treatment protocol;

FIG. 8A-8D are screen diagrams of the device of FIG. 5B and 5C, during operation of the device.

DETAILED DESCRIPTION OF GRAPHIC MATERIALS

In FIG. 1 shows an exemplary embodiment of the invention, wherein a base-shaped electronic device 100 (electronic device 100, otherwise spelled base, the terms being used interchangeably herein) receives a mobile computing device, such as a smartphone 102, including a display device. screen 103, made with the possibility of direct connection to optics, as well as electronic and/or information communication. The base 100 and the smartphone 102 may also be connected to each other via communication networks, such as a wide area network or a public network, such as the Internet. Connections via near-field communications and other electronic communication formats, and direct links through the input/output (I/O) port of the communication module 254 (FIG. 2) are also permitted.

The base 100 includes one port 110 for receiving a disposable microfluidic technology sample preparation chip/cassette 112 that, for example, contains a blood sample for analysis, and another port 114 for receiving a biosensor strip 116 on which a blood sample is placed on the working end 116a, for example, at the electrode 116b. Ports 110, 114 are associated with channels. Port 110 serves as an input to a microscopic or optical or imaging channel (the terms "imaging channel", "microscopic channel" and "optical channel" are used interchangeably), for example, in the context of malaria detection, where a specific parasite (type of malaria) is identified and stages of malaria, as well as to fulfill requests for a complete blood count (OAK). Another port 114 serves as a signal channel or electrochemical channel (the terms "signal channel" and "electrochemical channel" are used interchangeably) for analyzing electrochemical signals from a blood sample at electrode 116b of biosensor strip 116 and, for example, for patients infected with malaria by detecting glucose-6-phosphate dehydrogenase (G6PD) deficiency to select the appropriate drug.

In FIG. 2 shows a block diagram of a base 100 and a smartphone 102. The base 100 and a smartphone 102 are shown coupled to each other and connected to one or more networks 200, such as local area networks (LANs) and wide area networks (WANs), including public networks such like the Internet, cellular networks and other communication networks.

Both channels, the imaging channel from port 110 and the signal channel from port 114, share a central processing unit (CPU) 202 with attached storage/memory 204, a base power supply 206, and a communications module 208 from which a USB header 209 (universal) extends. serial bus) or other similar connector.

A central processing unit (CPU) 202 is formed from one or more processors electronically and in communication with a storage/memory 204 that stores instructions executed by the CPU 202 to execute dual channel processes. Power supply 206 is a battery or plug-in power source. The communications module 208 provides network connectivity (e.g., the Internet) and communication with the base 100, in addition to providing a direct connection, for electronic and data communications between the base 100 and the smartphone 102.

The imaging channel includes a software port that receives a microfluidic chip 112 (FIG. 1), also known as a microfluidic device. The microfluidic chip 110 is viewed by optics 308 (FIG. 3), including an optical-mechanical system 212 and an optical transmission system 214, and terminated by an optical module lens 216 through which the image is transmitted. Optics 308, such as optical-mechanical system 212, magnify the sample and improve visual presentation, including images, allowing high micron resolution to be achieved.

The microfluidic chip 112 operates on the basis of capillary action, which allows the collected blood to be transported and stained for subsequent accurate study. The optomechanical system 212 (with controller 212a) scans the microfluidic chip 112 (scanning enabled by moving the stand/drawer 302 on scanning engine 304 (FIG. 3) by controller 212a) for microscopic viewing using an optical transmission system 214 that terminates in an optical module lens. 216. Also included in the design of the optomechanical system 212 is an indicator light (ID) 217 that can be controlled manually (via a switch, button, or other elements (not shown)) or by a controller 212a. The optomechanical system 212 and the optical transmission system 214 are coupled via electronic and/or data links, directly or indirectly, to the CPU 202, storage/memory 204, power supply 206, and communications module 208.

In FIG. 6A-6G show various microfluidic chips (microfluidic device) 112a-112g, which are embodiments of the microfluidic chip 112. These microfluidic chips 112a-112g are connected to the software port of the described device(s) 100, 500, 500'. Microfluidic chips 112a-112g shown in FIG. 6A-6G include substrates 601, 664, for example, glass or polymer or both, or other material with/without a hydrophilic coating suitable for interaction with blood and/or other fluids such as urine, and which may also include other components such as dyes for microscopy and other substances (solid, liquid or gas) such as powders from fragile capsules. The described instrument(s) 100, 500, 500' analyzes and/or displays the aforementioned fluids and/or fluids mixed with other components.

The microfluidic chip 112a shown in FIG. 6A includes a substrate 601 of glass or polymer or both, or other material with or without a hydrophilic coating suitable for interaction with blood and/or other fluids such as urine, and which may also include other components, for example , dyes, for microscopy and other substances (solid, liquid or gaseous), such as powders from fragile capsules. The substrate 601 has a blood inlet 602 and a dye enclosed in a blister 604 at one end 601a of the substrate 601. Pressure on the blister 604 causes the tunnel side of the blister 604 to rupture, causing the dye to pass through the microfluidic tunnel 606 Blood and/or diluted blood and dye flow through the microfluidic channel 606 into a coil-shaped microfluidic channel 608, which serves as a blood and dye mixing zone 610. The blood and dye mixture continues to flow through another microfluidic channel 612 into a viewing chamber 614 at the opposite end 601b of the substrate. The viewing area 614 is made on the substrate 601 with the possibility of combining with the optics 308 of the optomechanical system 212 of the device 100, 500.

The microfluidic chip 112b shown in FIG. 6B includes a support 601 made of a material suitable for reacting with blood and other components, such as dye, wash solution, for microscopy. The substrate 601 contains a blood inlet 622, a dye contained in a blister 624, and a wash solution contained in a blister 626 at one end of the substrate 601a. In use, blood from the blood inlet 622 flows through the microfluidic channel 628, causing blood cells to adhere to the walls of the microfluidic channel 628. Pressure on the blister 624 causes the blister 624 to rupture, causing dye to flow through the microfluidic channel 628 through the adherent cells. blood. As a result, the dye and cells reach the staining and viewing zone 630 on the substrate 601. The staining and viewing zone 630 is made on the substrate 601 with the possibility of combining with the optics 308 of the optomechanical system 212 of the device 100, 500. Next, under the influence of pressure on the blister 626, the blister 626 ruptures, causing the cleaning solution to flow through the microfluidic channel 628, removing any remaining dye and diluting the dye/blood mixture.

The microfluidic chip 112c shown in FIG. 6C includes a support 601 made of a material suitable for reacting with blood and other components, such as dye, for microscopy. The substrate 601 is provided with a blood inlet 642 (at one end 601a of the substrate 601) located at the end of a microfluidic channel 644 that terminates in a staining and viewing chamber 646 (at the other end 601b of the substrate 601). The camera 646 for staining and viewing is made on a substrate 601 with the ability to combine with the optics 308 of the optomechanical system 212 of the device 100, 500, 500'. The dye is contained in a dry state within the walls of the microfluidic channel 644 such that when blood or diluted blood 647 flows through the microfluidic channel 644 into the staining and viewing area, the blood 647 picks up the dye. This microfluidic chip 112 is typically used to view individual red blood cells. Here the microfluidic channel is shallow, about 10 micrometers in diameter, since the blood is not diluted.

The microfluidic chip 112d shown in FIG. 6D includes a substrate 601 made of a material suitable for contact with blood and other components. The substrate 601 at one end 601a contains a sample inlet 652, which is connected to a microfluidic channel 654, which in turn is connected to and terminates at the viewing chamber 656 at the other end 601b of the substrate 601. Blood sample, diluted or undiluted form mixed with dye 657 is placed into sample inlet 652 where the dyed sample enters viewing area 656. The viewing camera 656 is made on a substrate 601 with the ability to combine with the optics 308 of the optomechanical system 212 of the device (devices) 100, 500, 500'.

Let us now turn our attention to FIG. 6E-1A, 6E-1B, 6E-2, 6E-3, 6E-4, 6E-5 and 6E-6 (6E-1A-6E-6), which depict another microfluidic chip 112e for devices 100, 500 , 500'. The mixing chamber 662 extends into the substrate 664 from a first side 666a, such as a top side on the top surface 666a, to a base 668. The base 668 is partially surrounded by a main channel 670 on a second side 666b, such as a bottom side. The base 668 is an extension of the mixing chamber 662 and acts as a pressure equalization reservoir, for example to collect excess blood and dye mixture. The base portion 668x is surrounded by the main channel 670, and together they act as connected vessels during mixing of blood stains. The main channel 670 is U-shaped with a main C-shaped portion 670a with outwardly extending portions 670b that form the beginning of the channel 670 and, for example, serve as a receiving area for blood and other fluids. The first side 666a and the second side 666b, for example, lie opposite each other.

Inlet/outlet channels 672 terminate in holes 673, each of which extends from a corresponding flared portion 670b of the main channel 670. In operation, blood/liquid is introduced from the hole 673 through the channel 672, where the blood/liquid fills the main channel 670 by capillary forces.

A scan channel 674, compatible with the optomechanical systems optics 308 of the corresponding device 100, 500, 500', extends from the main channel 670 through the substrate 664 to the pressure relief channel 676. The scanning channel 674 is oriented, for example, substantially perpendicular or perpendicular to the pressure relief channel 676. The pressure release passage 676 ends at an opening 678 that is initially sealed. In operation, the hole 678 is pierced to open to the environment at, for example, ambient pressure, creating an air inlet/outlet such that blood (or fluid) and/or a blood (or fluid)/dye mixture (which may also include other substances, such as frangible capsule powder, as detailed below) fills scan channel 674.

The mixing chamber 662 extends into the substrate 664 in the shape of an internally tapered (from first side 666a to second side 666b) frustocone that is, for example, rounded, substantially circular, or circular, although other shapes, including tapered shapes internally, are also acceptable. The wall 680 of the mixing chamber 662 is formed by overlapping (alternating) plates 682 or protruding elements. The plates 682 provide cohesion for mixing when an item, such as a frangible or rupture capsule, is placed in the mixing chamber 662.

The wall 680 extends into the substrate 664 such that the plates 682 terminate at the main channel 670, at the first or top wall 684 of the main channel 670. The main channel 670 also includes an outer wall 685 that connects to the base 668 (the base 668 forms the third or bottom channel wall 670, with this third wall 668 located opposite the first wall 684). The outer wall 685 is substantially perpendicular or perpendicular to the first wall 684 and the base 668 such that the main channel 670 opens along one side, as shown in FIG. 6E-4 and 6E-5. This three-wall configuration 684 (first or top wall), 685 (second or outer wall), 668 (third or bottom wall) allows the main channel 670 to retain blood and/or other fluids through capillary action and/or surface tension. Likewise, the scan channel 674 also facilitates the movement of blood/fluid through capillary action.

The 664 substrate is made of plastic, making it optically transparent. The plates 682 (forming the wall of the chamber 680) are made of an elastomeric material that is, for example, flexible and resilient. All of the above materials can be sterilized by heat and similar methods.

FIG. 6E-6 is a photograph of the second side 666b of the microfluidic chip 112e, which shows that the main channel 670 has been filled with blood and/or liquid (which may also include dye and/or other substances) by capillary action.

In FIG. 6F shows another embodiment of microfluidic chip 112f including a substrate 664. The design of this microfluidic chip 112f is similar to that of chip 112e in FIG. 6E-1A-6E-6, with corresponding structures assigned the same element numbers and description as the detailed description for microfluidic chip 112e above, except where noted. This microfluidic chip 112f includes two mixing chambers 662 and channel structures as described above for microfluidic chip 112e, but also has a fluid inlet 686. The fluid inlet 686 is in fluid communication with support channels 688 and 688a , which lead to the main channels 670 of the corresponding mixing chambers 662. The scanning channels 674 are configured to align with the optics 308 of the optomechanical systems of the corresponding instrument 100, 500, 500'. Scan channels 674 terminate in pressure channels (not shown) that terminate in holes 678, as detailed in the microfluidic chip 112e.

In FIG. 6G shows another embodiment of the microfluidic chip 112g that has a rounded shape. Elements similar to those of the microfluidic chips 112e, 112f are assigned the same element numbers and correspond to the above descriptions for the corresponding microfluidic chip 112e, 112f, except where otherwise noted. The microfluidic chip 112g is formed from a substrate 664 and has two mixing chambers 662 that overlap the main channels 690, similar to the main channels 670 in that they are also U-shaped with outer extensions. Blood/fluid enters a fluid inlet 692 that is hydraulically connected to support channels 693, which in turn are hydraulically connected to the main channels 690 of the respective mixing chambers 662. Test channels 694, which are also support channels, are connected to the corresponding support channels 693.

The main channels 690 are hydraulically connected to the scanning channels 696 and start from the mixing chambers 662. The scanning channels 696 are then rounded, with the rounded portions 696a matching the rounded shape of the microfluidic chip 112g and the substrate 664. The scanning channels 696 (including portions 696a) are configured to be aligned with the optics of the optomechanical systems of the corresponding device. Pressure relief passages 698 extend from scan path 696 at rounded portions 696a. The pressure relief channels 698 are oriented, for example, substantially perpendicular or perpendicular to the scan channels 696. Each pressure relief channel 698 ends in an opening 699, which remains closed until opened, as detailed above for the opening 678.

Returning to FIG. 6E-1A-6E-6 and microfluidic chip 112e, now we will describe an example of the operating procedure. The microfluidic chips 112f, 112g operate similarly, and the operating description for the microfluidic chip 112e is applicable to the microfluidic chips 112f, 112g. Initially, blood or other fluid (hereinafter referred to as blood for describing an operating example) is obtained and placed in the main channel 670 (fluid inlet 686 of the microfluidic chip 112f and fluid inlet 692 of the microfluidic chip 112g). Once in the main channel 670, blood fills the main channel 670, moving through it by capillary action.

The rupture capsule or other substance is placed in the mixing chamber 662 and crushed, for example, by applying pressure to the mixing chamber 662. The capsule reagent is mixed with blood in the main channel 670. The opening 678 of the corresponding pressure relief channel 676 opens under ambient pressure so that mixed blood/substance fills the scanning channel 674, for viewing the analysis using the optics of the device (device) 100, 500, 500'.

The signal channel originates from port 114 and includes a biosensor reader 222 that reads the electrical response (generated electrical current from the electrochemical reaction between the sample and electrode 116b output from electrode 116b/biosensor strip 116 as an analog signal) from the disposable biosensor electrode 116b (eg, at the operating end 116a of the biosensor strip 116) and amplifies the analog electrical response signal, wherein the analog signal is indicative of an electrochemical response to a disease, condition, measurement, or the like. There is an analog-to-digital converter (ADC) 224 that converts analog signals from the reader 222 to digital signals, a signal analysis software module 226 that analyzes the digital signals to detect G6PD deficiency in a particular sample, and which communicates with the communication module 208 to send the signals to smartphone 102 for additional analysis.

The signal channel can also be used to determine blood glucose levels. Biosensor reader 222 is further configured to amplify the analog signal(s) generated by the electrical response from the disposable biosensor electrode (eg, biosensor strip 116). Analog signals correspond to blood glucose levels. An analog-to-digital converter (ADC) 224 converts the analog signals from the reader 222 into digital signals, and a signal analysis module 226 analyzes the digital signals received from the ADC 224 to determine the glucose level in the blood sample. This blood glucose level is output in accordance with standard blood glucose measurements to communication module 208, with subsequent signals being sent to smartphone 102 for further analysis and for presentation on a display screen (smartphone 102 or stand-alone device 500, 500' (FIG. 5A and 5B)).

Also, biosensor strips 116 may include a plurality of biosensor electrodes 116b, including electrodes for receiving electrical responses converted into signals readable to detect G6PD deficiency and blood glucose levels at the same time and, for example, simultaneously.

In other embodiments, the signaling channel may be used to analyze other conditions, such as other diseases, pathogens, or biomarkers. Biosensor reader 222 is further configured to amplify or otherwise modify analog signals generated by the electrical response (electrochemical response) from an electrode on the disposable biosensor strip. The electrode on the biosensor strip is configured to create an electrochemical reaction when the sample comes into contact with a condition, wherein the electrochemical reaction creates a current and a corresponding analog signal to identify the condition (the biosensor reader is configured to recognize the electrochemical signatures (or electrochemical responses) of these conditions, and amplifies the resulting analog signal caused by an electrochemical response). An analog-to-digital converter (ADC) 224 converts the analog signals from the reader 222 into digital signals, and a signal analysis module 226 (programmed to determine a condition, such as the presence or absence of a condition), analyzes the digital signals received from the ADC 224 to determine the condition. Data about the detected condition is output to the communication module 208 to send signals with the results to the smartphone 102 for presentation on the display screen (smartphone 102 or stand-alone device 500, 500' (FIGS. 5A and 5B)).

A device, such as a smartphone 102, includes both microscopic channel and signal channel portions. The smartphone 102 includes a common central processing unit (CPU) 242 with attached storage/memory 244, a display screen module 246 that includes logic for controlling the display screen 103 of the smartphone 102, a global positioning system (GPS) module 248, a data storage 250, for example, a RAM (random access memory), a sensor 252 such as a gyrometer, a temperature meter, a magnetometer, and an accelerometer forming an inertial measurement unit (IMU), and a communications module 254 including a USB (Universal Serial Bus) 255 female connector or other similar connector for connecting plug connector 209 for electronic data interchange and/or data transmission. The GPS or location module 248 is intended to provide real-time location indications based on a built-in GPS unit (smartphone 102 or as part of a stand-alone GPS device or location module 548) by mapping the disease to be used for real-time mapping and epidemiological monitoring and study. diseases such as malaria.

There is also a camera/image sensor unit 260 for converting the camera image into signals for display on the display screen 103 (via display screen module 246), an analysis module 264 for analyzing the image to determine, for example, the type of malaria parasite (e.g., Plasmodium, falciparum, P. vivax, P. malaria, P. ovale, P. knowlesi and disease stage) and label data associated with a specific blood sample. The analysis module 264 may also be programmed to analyze and detect other diseases and conditions, including a complete blood count, a multidetection test (eg, relapsing fever, filaria), sputum microscopy for tuberculosis, urinalysis, Pap smear testing, and similar tests. , as well as identifying veterinary diseases and conditions.

Both base 100 and smartphone 102 connect via network(s) 200 to cloud server 270, to which frame samples of the malaria parasite are transferred (directly or from data warehouse 250) to update the machine learning of analytics module 264 as a whole. With each new frame sample, cloud server 270 sends updated machine learning to analysis module 264, thereby improving the malaria parasite detection process. This is done online or offline when a connection is available, automatically or on demand. Cloud server 270 also, for example, stores each received test record, time, location, diagnosis (both parasite and G6PD), patient information and symptoms, and more, both on machine 102 and, optionally, diagnosis from the vendor 280 telemedicine services, display screen and other information, and can structure malaria cases in real time. All data storage and data communications over networks 200 between base 100, smartphone 102, cloud server 270, telehealth provider computers 280a, 280b are HIPAA (Health Insurance Portability and Accountability Act) compliant.

Base 100 and smartphone 102 are also connected, for example, through network(s) 200 to telehealth provider 280, computer 280a, or smartphone 280b (via cell tower 282). Telehealth provider 280 may provide diagnostics that are sent either to cloud server 270 or back to analytics module 246 of smartphone 102 .

In FIG. Figure 3 shows the diagrams of the image forming channel and the signal channel. These channels are partially connected to both the base 100 and the smartphone 102.

The microscopic channel originates at port 110, to which a microfluidic chip 112 is connected. Under capillary action, this chip 112 distributes the blood sample, stains it, and separates the blood cells. The optomechanical system 212 includes a stand or slide-out panel 302 that holds the microfluidic chip 112. The stand/slide-out panel 302 is located on a scanning mechanism 304 controlled by a controller 212a that allows the chip 112 to be manipulated in various positions (in the form of a bidirectional oval arrow 306) according to data obtained from the optics 308 of the optical transmission system 214, which ends in a lens 216 or the like. The screening mechanism (consisting of the stand/drawer 302 and the scanning mechanism 304), for example, is based on the movement of the drawer 302 or is optically shielded based on an optical design, such as using a mirror or prisms (which are part of the optical transmission system 214).

The image from the optics 308 (including light 309 (similar to light 217 detailed above)) of the optical transmission system 214 is transmitted to the lens 320 of the camera 260 of the smartphone 102 or to a stand-alone image sensor in the case of a stand-alone device. The image from the camera 260 is converted into signals by the image sensor unit 262, with the output signals being input to the analysis module 264. The output signals are also input from the analysis module 264 to the display screen module 246 such that the blood sample is displayed on the display screen 103.

An analytics module 264 trained in processes including image analysis, machine learning, and artificial intelligence (AI) to identify a disease or condition and provide a protocol for diagnosing and/or treating the identified disease or condition. In addition, the CPU 202 serves to provide a protocol for diagnosing and/or treating an identified disease or condition. This detection and/or diagnosis of a disease and/or condition is based, for example, on morphological analysis of “biomarkers” of parasites at different stages and types. The algorithm (executed by controller 212a) includes image processing capabilities (in software and/or hardware), segmentation capabilities (in software and/or hardware), filters, and specific morphological comparisons with known and collected data from the RevDx system. The resulting diagnostic data is stored in a data store 250 and/or a cloud server 270. For example, it is also transmitted to a telemedicine service provider 280 for confirmation.

The signal channel originates at port 114. A blood sample on biosensor strip 116 is placed at port 114, and the electrical response (electrochemical response) resulting from the electrochemical reaction generates correlated analog signals. The analog signals are read by biosensor reader 222, which amplifies the correlated analog signal. Biosensor reader 222 amplifies and, in some cases, filters the analog signal, which is converted to a digital signal by an analog-to-digital converter (ADC) 224. The output of the digital signals from the ADC 224 is input to a signal analysis module 226, which analyzes the digital signal input, e.g. for G6PD deficiency. Data corresponding to the presence of G6PD from the sample is sent by the signal analysis module 226 to the communication module 208 and then to the communication module 254 of the smartphone 112. Now in the smartphone 112, data is sent from the communication module 254 to the analysis module 264, where analysis is performed for the recommended drug on based on known treatment procedures. The analysis module 264 provides a signal to the display screen module 246 to display on the display screen 103 a graphical list indicating whether G6PD deficiency exists and the malaria parasite type, species, density, stage, and other factors.

Also, if the signal channel is configured to output blood glucose readings as detailed above, such blood glucose readings may be obtained with or separately from the G6PD output, depending on the electrode(s) 116b on the biosensor strip 116. For example, the G6DP result in combination with the glucose level is analyzed by the CPU 202 to determine a treatment protocol, for example, as shown in FIG. 7. Treatment protocols, as well as the presence of a disease or condition, are displayed on display screens, a smartphone 103, or a stand-alone device 500, 500' as a user interface (UI) as indicated by the CPU 202 in the described devices 100, 500, 500'.

The final decision regarding the treatment protocol for malaria, if malaria is detected, is based on microscopic and signal channel analysis. This analysis is performed automatically by an algorithm (run, for example, by CPU 202) on site within minutes or, in case of uncertainty, the data can be sent over the Internet and analyzed remotely by telehealth provider 280 via networks 200.

Likewise, if the signaling channel is to detect other indications of diseases and conditions from the blood, including G6PD output, blood glucose testing, or urine testing. One or more of the above indicators are analyzed together in accordance with the program provided by CPU 202 to determine the treatment protocol.

Let us now turn our attention to FIG. 4A and 4B, which depict block diagrams detailing computer processes in accordance with embodiments of the subject matter described. Reference is also made to the elements shown in FIG. 1-3. The process and sub-processes in FIG. 4A and 4B are computerized processes performed by the system in accordance with the invention, and, for example, they are performed manually and/or automatically and, for example, in real time.

In FIG. 4A is a flow diagram of an example microscopy process for a microscopic channel in accordance with the invention. First, a blood sample is obtained and placed on a microfluidic chip, such as the microfluidic chip 112 detailed above, and the blood is stained using the microfluidic chip 112 placed in the base 100 through the port 110, at block 402. Via an optical transmission system (optical transmission) 214 at block 404, the microscopic image of the blood sample stained on the microfluidic chip reaches the camera 260 of the smartphone or stand-alone device 102. The image in the camera/image sensor block 260 is converted into digital data, such as digital signals, at block 406. The digital data is analyzed at block 408 by the module software analysis 264 using machine learning and artificial intelligence (AI). Analysis module 264 reports the diagnosis at block 420. Additionally, at block 420, an image of the blood sample is displayed on display screen 103 via display screen module 246. From block 408, the process may proceed to block 470, where it terminates.

When moving from block 420 to block 430, the results of the analysis of the blood sample, including the visual image, may be flagged by the analysis module 264 (optional).

From block 430, a process may move one or more of the three optional paths defined by the block in series 440, series 450, and series 460.

When moving from block 430 to block 440, the labeled sample analysis results may be stored, for example, in data store 250. The labeled data may then be sent from the store to a cloud server, such as cloud server 270, at block 442, or directly to the cloud server. 270, from block 430 to block 442. At block 442, cloud server 470 updates machine learning, artificial intelligence (AI) data and diagnostics for the image. The process moves to block 444, where the analysis module 264 is updated with this new data. The process then moves to block 470 where it ends.

When moving from block 430 to block 450, the tagged sample test results or stored tagged sample test results (from block 440) in an optional process may be sent, for example, transmitted over the network 200 to the telemedicine specialist 280, for example, to his computer 280a or smartphone, tablet, laptop 280b, etc. Block 452 receives a diagnosis from telehealth provider 280, for example, on smartphone 102, after which the process moves to block 470, where it ends, or to cloud server 270. Once received at cloud server 270, the process moves to block 444, where the analytics module 264 is updated with this new data, or to block 460, detailed below. From block 444, the process moves to block 470, where it ends.

At block 460, reached from either block 430 or block 452, the sample, based on the GPS tag and timestamp, may be further displayed, for example, by cloud server 270. The process may proceed to an optional process at block 462, where the cloud server 270 provides a map of all analysis results. The process then moves to block 470 where it ends. The process may also move from block 460 to block 470, where it ends.

In FIG. 4B is a flowchart describing the flow of an exemplary signal processing process for a signal channel in accordance with the invention. Initially, at step 412, a blood sample is obtained and placed on a biosensor strip, such as the biosensor strip 116 described in detail above. The biosensor strip 116 is placed in the base 100 through port 114 in block 402. The blood sample causes an electrochemical reaction that results in an electrical response output in block 414 in the form of an analog signal(s) that is read by the biosensor reader 222. This analog signal output, e.g. amplified by biosensor reader 222, input to analog-to-digital converter (ADC) 224 in block 416, which converts analog signals to digital signals. The digital signals are then input to signal analysis module 226, where the signals are analyzed, at block 418. The signals are then passed to analysis module 264, which reports the diagnosis, at block 420'. Additionally, at block 420', a graphical and absolute number indicating the G6PD deficiency condition is displayed on the display screen 103 via display screen module 246. From block 418, the process may proceed to block 470, where it ends.

From block 420', the process may move to optional processes of block 430, 440, 442, 444, 450, 452, 460, 462 and ultimately terminate at block 470, as detailed above.

In FIG. 5A and 5B illustrate alternative mobile computing devices 500, 500' for performing the described processes via a microscopic channel and a signal channel. Devices 500, 500' include components identical or similar to those in device 100, have the same part numbers, and are as described above for device 100 of FIG. 2. Components including display screen module 546 (which drives display screen 503, such as device touch screen 500), location-based GPS module 548, data storage 550, IMU sensors 552, image sensor module 562, and analytics module 564 are identical or similar to the corresponding components on the smartphone 102 of FIG. 2, but have element numbers of 500 (rather than 200 in FIG. 2) and correspond to the corresponding component number in FIG. 2. Analysis module 564 analyzes the scanned sample, for example, using image identification, artificial intelligence and the like, determining the presence or absence of a disease and/or condition (for example, diagnosis of malaria parasites) or measurement (for example, blood glucose and general analysis blood). Optical transmission system 214 is optional because device 500 (FIG. 5A) can operate as a standalone device that does not require lens 216 and optical transmission system 214, or with a smartphone or other device that may require optical transmission system 214 and lens 216 The device 500' (FIG. 5B) lacks an optical transmission system 214 and a lens 216, and as such operates solely as a stand-alone device.

FIG. 5C shows a device 500' operating as a stand-alone unit, including a display screen 503 showing a screenshot 580. This device 500' is hand-held and therefore portable and battery operated and can also be recharged from an external power source and solar energy.

In FIG. 7 illustrates a process in the form of a decision diagram, for example, programmed (and executed) by the CPU 202 of devices 100, 500 and 500' to support treatment decisions (eg, provide treatment recommendations, treatment protocols, and the like). Recommendations and treatment protocols appear, for example, as user interfaces (UIs) on display screens, such as interfaces on the display screen 503 of the autonomous device 500' displayed as display screens (screenshots) 580a-580d in FIG. 8A-8D4; A detailed description is given below.

In the first step of the process, if malaria is detected, the blood glucose level is checked at block 702 to determine whether the patient is hypoglycemic at block 704. If a positive result is obtained, treatment with artemisinin combination therapy (ACT) is proposed at block 706 At block 708, if primaquine is used to prevent further transmission, a test for G6PD deficiency may be performed using the devices 100, 500, 500' described herein.

In the second step of the process, if non-tropical malaria or mixed infection is detected, block 712 offers treatment with ACT and chloroquine, as well as testing for G6PD using devices 100, 500, 500' described herein in block 714. If G6PD test result is negative; treatment with primaquine is recommended in block 716.

In the third step of the process, if the test result is negative for tropical and non-tropical malaria, it is recommended to retest with devices 100, 500, 500' according to the scheme described above, with a high clinical suspicion of the patient in block 722.

In FIG. 8A shows device 500' with a screenshot 580a displaying a malaria test result and a proposed treatment protocol. In FIG. 8B shows device 500' with a screenshot 580b displaying a malaria test result and medication information that may come from CPU 202 or cloud server 270. FIG. 8C shows the device 500' with a screenshot 580 s showing a detailed white blood cell count. In FIG. 8D shows device 500' with screenshot 580d showing detailed red blood cell counts.

Although the devices and methods described above relate to diseases such as malaria, these devices can also be used to diagnose other diseases and blood parameters, such as white blood cell/red blood cell count and white blood cell differentiation, with various modules programmed to recognize white blood cells/ erythrocytes and the formation of analytical data on them.

Implementation of the method and/or system of embodiments of the invention may involve performing or completing selected tasks manually, automatically, or a combination of both. Moreover, in accordance with the actual instrumentation and equipment of embodiments of the method and/or system in accordance with the invention, several selected tasks may be implemented by hardware, software or firmware or a combination thereof using an operating system.

For example, hardware for performing selected tasks according to embodiments of the invention may be implemented in the form of a chip or microcircuit. As software, selected tasks in accordance with embodiments of the invention may be implemented as a plurality of program instructions executed by a computer using any suitable operating system. In an exemplary embodiment, one or more tasks in accordance with exemplary embodiments of a method and/or system as described herein are performed by a data processor, such as a computing platform, configured to execute a plurality of instructions. Optionally, the data processor includes volatile memory for storing instructions and/or data and/or non-volatile memory, such as read-only storage media such as a magnetic hard disk and/or removable storage media, for storing instructions and/or data. An optional network connection is also provided. It is also possible to provide a display and/or a user input device such as a keyboard, mouse or printer.

For example, any combination of one or more non-transitory computer-readable media may be used in accordance with the above-listed embodiments of the present invention. The non-transitory computer-readable (information) medium may be a computer-readable signal medium or a computer-readable information medium. A computer-readable storage medium may be, but is not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, instrument, or device, or any suitable combination thereof. More specific examples (a non-exhaustive list) of computer-readable storage media may include the following: an electrical connection having one or more wires, a laptop computer floppy disk, a hard disk drive, random access memory (RAM), read-only memory (ROM), erasable EPROM (EPROM or flash memory) ), fiber optic, portable compact disc read-only memory (CD-ROM), optical storage device, magnetic storage device, or any other suitable combination of the foregoing. As used herein, a computer-readable storage medium may be any tangible storage medium that can contain or store a program for use or execution of a command by a system, instrument, or device.

The computer-readable signal medium may include a distributed information signal with machine-readable program code, for example, in a baseband or as part of a carrier wave. Such propagated signal may take any of a variety of forms, including, but not limited to, electromagnetic, optical, or any suitable combination thereof. A computer-readable signal medium can be any computer-readable medium that is not a computer-readable information medium and that can transmit, distribute, or transport a program for use by a system, device, or execution of a command by a system, device, or device.

With reference to the sections and figures presented above, it should be understood that various embodiments of computer methods are presented herein, some of which may be implemented by various embodiments of the instruments and systems described herein, and some of which may be implemented in accordance with with instructions stored on non-volatile machine-readable media described in this document. However, certain embodiments of the computerized methods described herein may be performed by other devices or systems and may be performed in accordance with instructions stored on computer-readable media other than those described herein, at the discretion of those skilled in the art. technical field with reference to the described embodiments. Any reference to systems and computer-readable media with respect to the following computerized methods is for explanatory purposes and is not intended to limit any of such systems and any of such non-transitory computer-readable media with respect to the embodiments of the computerized methods described above. Likewise, any reference to the following computerized methods with respect to systems and computer-readable media is provided for explanatory purposes and is not intended to limit any of such computerized methods described herein.

The process diagram and block diagrams in the figures illustrate the architecture, functionality and operation of possible implementations of systems, methods and computer program products in accordance with various embodiments of the present invention. As such, each block in a process diagram or flowcharts may represent a module, segment, or portion of code that contains one or more executable instructions to implement specified logical function(s). It should also be noted that in some alternative implementations, the functions noted in the block may occur in the order shown in the figures. For example, two blocks that follow one another may actually be executed simultaneously, or blocks may sometimes be executed in reverse order, depending on the functionality involved. It should also be noted that each block of the process diagram and/or flowcharts and combinations of blocks in the process diagrams and/or flowcharts may be implemented by special-purpose hardware systems that perform the specified functions or actions, or combinations of special-purpose hardware and computer instructions.

Descriptions of various embodiments of the present invention have been presented for illustrative purposes and are not intended to be exhaustive or limiting of the described embodiments. Many modifications and changes will become apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terms used herein are intended to describe as accurately as possible the principles of the embodiments, practical application or technical improvement over technologies available in the market, or to enable others skilled in the art to understand the embodiments described herein.

For the purposes of this document, singular forms include the plural unless the context clearly requires otherwise.

The word “illustrative” is used herein to mean “serving as an example, example, or illustration.” Any embodiment described as “illustrative” should not necessarily be considered preferred or superior to other embodiments and/or preclude the inclusion of features from other embodiments.

It is understood that certain features of the invention, which for clarity are described in the context of individual embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which for brevity are described in the context of one embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments should not be considered essential features of those embodiments unless the embodiment operates without those features.

The above processes, including portions thereof, may be performed by software, hardware, or combinations thereof. These processes and portions thereof may be performed by computers, computer-type devices, workstations, processors, microprocessors, other electronic retrieval tools and memories, and other temporary storage devices associated therewith. The processes and portions thereof may also be embodied in programmable non-volatile storage media, such as compact discs (CDs) or other disks, including magnetic, optical, etc., machine readable or similar devices, or other usable storage media, including magnetic , optical or semiconductor storage devices or other electronic signal sources.

The processes (methods) and systems, including their components, are described with illustrative reference to specific hardware and software. The descriptions of processes (methods) are illustrative in nature, which allows those skilled in the art to omit and/or change individual steps or their order, limiting these embodiments in practice without undue experimentation. The processes (methods) and systems have been described so that those skilled in the art can easily adapt other hardware and software that may be required to practice any of the embodiments without additional experimentation and the use of conventional techniques.

Although the invention has been described in connection with its specific embodiments, it will be appreciated that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is capable of including any such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

Claims (8)

1. A microfluidic device for preparing a blood sample for analysis, comprising a substrate including opposite first and second sides; a chamber extending into the substrate from the first side to the second side to a base, the chamber including projecting members forming a wall of the chamber; and a main channel extending along at least a portion of the chamber wall along the base of the chamber, characterized in that the chamber has a conical shape such that the chamber tapers inward from the first side to the second side, the projecting elements include overlapping plates forming the wall chambers, and the main channel is located between the plates forming the wall and base. 2. Microfluidic device according to claim 1, characterized in that the plates are made of flexible and elastic material. 3. Microfluidic device according to claim 1, characterized in that the main channel is C-shaped and corresponds to the shape of the periphery of the chamber wall. 4. The microfluidic device according to claim 3, characterized in that the main channel contains opposite upper and lower walls with an outer wall that is located between the upper and lower walls. 5. Microfluidic device according to claim 4, characterized in that the outer wall is perpendicular to the opposite upper and lower walls. 6. The microfluidic device of claim 5, wherein the main channel is sized to promote capillary action to move the blood sample through the main channel. 7. The microfluidic device of claim 1, wherein the first side comprises a surface and the chamber extends into the substrate from the surface. 8. The microfluidic device according to claim 1, characterized in that the channel extending from the main channel is capable of communicating with the environment through an opening opening and being filled with a blood sample from the main channel.