A method for controlling timing of events in a microfluidic device and a timer microfluidic device

Abstract

A method for controlling timing of events in a microfluidic device and a timer microfluidic device are disclosed. The method comprises adding a liquid on a first end of a microfluidic device at a first time t.sub.0, the liquid flowing by capillarity towards a second end; producing, by a battery (12) included in the microfluidic device, energy from a second time t.sub.start until a third time t.sub.end to feed an auxiliary device (16) connected to the battery (12). The battery (12) is sized and composed to provide a given amount of energy during a delivery energy time interval t.sub.operation, comprised between a time t.sub.on in which a voltage output of the battery (12) is above a threshold and a time t.sub.off in which the voltage output is below the threshold, to control the duration of an event including a selective activation and deactivation of said auxiliary device (16).

Claims

1. A method for controlling timing of events in a microfluidic device, the method comprising: adding an amount of liquid on a first end of a microfluidic device at a first time t.sub.0, the liquid flowing by capillarity towards a second end of the microfluidic device; producing, by a paper-based battery, energy from a second time t.sub.start until a third time t.sub.end to feed an auxiliary device connected to the battery, the battery being included in the microfluidic device and being activated upon the addition of the liquid, the battery further having a paper part placed in contact with at least two electroactive electrodes, an oxidizing anode and a reducing cathode, said second time t.sub.start corresponding to the moment when the battery is wetted and said third time t.sub.end corresponding to the moment when the battery is discharged; and designing the battery to operate only for a delivery energy time interval t.sub.operation by modifying an active area of the battery, by modifying a thickness of the anode of the battery, and/or by connecting a discharge load either passive or active to the battery, so that the battery controls the duration of an event including a selective activation and deactivation of the auxiliary device connected to the battery only during said delivery energy time interval t.sub.operation of the battery, said delivery energy time interval t.sub.operation being comprised between a time t.sub.on in which a voltage output of the battery is above a threshold voltage and a time t.sub.off in which the voltage output is below the threshold voltage.

2. The method of claim 1, wherein the oxidizing anode comprises redox species, metals, alloys or polymers, and the reducing cathode comprises an air-breathing cathode, redox species, metal, alloys or polymers.

3. The method of claim 1, wherein the microfluidic device comprises a microfluidic analytical device including a lateral flow assay device further including a sample pad located at the first end and a lateral flow test strip through which the liquid flows by capillarity, the liquid comprising a liquid sample.

4. The method of claim 1, wherein the auxiliary device when activated during the delivery energy time interval t.sub.operation indicates an enabling time in which a result of an assay has to be taken.

5. (canceled)

6. The method of claim 1, further comprising using an electrical circuit to switch on/off a delivering of power of the battery when a given voltage level is reached.

7. The method of claim 1, further comprising adjusting a delay time t.sub.delay, which is comprised between said first time t.sub.0 and the delivery energy time interval t.sub.operation, by modifying a length of said paper part.

8. A timer microfluidic device, comprising: a first end adapted to receive an amount of liquid at a first time t.sub.0, the microfluidic device having a second end towards which the liquid flows by capillarity, and a liquid activated paper-based battery having a paper part placed in contact with at least two electroactive electrodes, an oxidizing anode and a reducing cathode, the battery being configured to produce energy from a second time t.sub.start until a third time t.sub.end to feed an auxiliary device connected to the battery, said second time t.sub.start corresponding to the moment when the battery is wetted and said third time t.sub.end corresponding to the moment when the battery is discharged; wherein the battery is designed to operate only for a delivery energy time interval t.sub.operation by modifying an active area of the battery, by modifying a thickness of the anode of the battery, and/or by connecting a discharge load either passive or active to the battery, so that the battery controls the duration of an event including a selective activation and deactivation of the auxiliary device connected to the battery only during said delivery energy time interval t.sub.operation of the battery, said delivery energy time interval t.sub.operation being comprised between a time t.sub.on in which a voltage output of the battery is above a threshold voltage and a time t.sub.off in which the voltage output is below the threshold voltage.

9. The device of claim 8, wherein the oxidizing anode comprises redox species, metals, alloys or polymers, and the reducing cathode comprises an air-breathing cathode, redox species, metal, alloys or polymers.

10. The device of claim 8, wherein the microfluidic device comprises a lateral flow assay device comprising a sample pad located at the first end and a lateral flow test strip through which the liquid flows by capillarity, the liquid comprising a liquid sample.

11. The device of claim 8, wherein the auxiliary device (16) comprises a lighting system including a Light Emitting Diode (LED), an audible system including a loudspeaker, a buzzer or an alarm, and/or a device transmitting a radiofrequency signal.

12. The device of claim 8, wherein the auxiliary device (16) comprises a window configured to be opened for a vision there through during said delivery energy time interval t.sub.operation and configured to be disabled thereafter, wherein said window comprises a mechanical window, a liquid crystal dispersion film or an electrochromic film.

13. The device of claim 8, wherein the auxiliary device comprises a heater, said heater being configured to be heated up until a given temperature during said delivery energy time interval t.sub.operation.

14. The device of claim 10, wherein the microfluidic device is placed inside a container.

15. The device of claim 14, wherein the container further integrates several additional devices to cooperate with the lateral flow test strip including an electrical discharge load including a resistor or a digital or analog circuit, as well as switches.

16. The device of claim 8, wherein the auxiliary device comprises a heater, which is configured to perform cellular lysis or nucleic acid amplification.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The previous and other advantages and features will be more fully understood from the following detailed description of embodiments, with reference to the attached figures, which must be considered in an illustrative and non-limiting manner, in which:

[0040] FIG. 1 is a schematic view of a lateral flow test strip according to the state of the art.

[0041] FIG. 2 is a schematic illustration of the lamination of materials for lateral flow fabrication as per the state of the art.

[0042] FIG. 3 is a flow chart illustrating a method for controlling timing of events in a microfluidic device, according to an embodiment of the invention.

[0043] FIG. 4 graphically illustrates the timeline operation of the battery included in the microfluidic device.

[0044] FIG. 5 illustrates an example of a LED powered by the battery as a visual indicator of valid time to read result of a test/assay.

[0045] FIG. 6 illustrates an embodiment of the proposed timer microfluidic device.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0046] With reference to FIG. 3 therein it is illustrated the basic steps of a method for controlling timing of events in a microfluidic device according to the invention. According to this embodiment, in the method, step 301, a given amount of liquid is added on a first end (or inlet end) of the microfluidic device at a first time t.sub.0, the liquid flowing by capillarity towards a second end, e.g. an outlet end, of the microfluidic device. Then, step 302, when a battery 12 (for example as seen in FIG. 6) included in the microfluidic device becomes in contact with the liquid, the battery starts producing energy from a second time t.sub.start until a third time t.sub.end to feed an auxiliary device 16 connected to the battery 12. At step 303, a delivery energy time interval t.sub.operation of the battery 12 comprised between a time t.sub.on in which a voltage output of the battery 12 is above a threshold voltage and a time t.sub.off in which the voltage output is below the threshold voltage is used to control the duration of an event including a selective activation and deactivation of said auxiliary device 16.

[0047] Therefore, the battery 12 is a primary battery that is activated upon the addition of a liquid. The performance of the battery 12 in time is illustrated in FIG. 4. As can be seen in the figure, the battery 12 only start producing power after the moment it is wetted (t.sub.start) and it stops producing power when it is discharged (t.sub.end). The energy/power produced by the battery 12 can be used by one or more auxiliary devices 16 (see FIG. 5), which would turn on, for example, when the voltage output of the battery 12 is above the given threshold voltage (V.sub.threshold). The period of time when the battery 12 is producing a voltage above the threshold defines the operation time (t.sub.operation), which goes from t.sub.on to t.sub.off.

[0048] Preferably, the battery 12 comprises a paper-based battery with a metal-based anode (e.g. of Magnesium, Zinc, Aluminum, Lithium, stainless steel, composites, etc.) and an air-breathing cathode. The battery 12 is sized and composed to provide a given amount of energy (related to the duration of the time event to control) and can be fabricated following the same strategies and processes of a lateral flow assay: assembling different layers on a substrate and then cutting them transversally to generate multiple batteries. With this strategy, the battery 12 could be mounted on top of a lateral flow assay in a very simple and cheap way.

[0049] When the battery 12 is integrated in an assay, i.e. the microfluidic analytical device comprises a lateral flow assay device, the liquid which comprises a liquid sample is added at time t.sub.0, and there might be a time interval, adjustable, before the liquid reaches the battery (t.sub.battery). The delay time can be adjusted, for example, by modifying the length of the paper strip 13 that transports the liquid sample from the sample pad 11, located at the first end, see FIG. 5, to the battery 12.

[0050] Several configurations are possible to mount the battery 12 with respect to the microfluidic device. For example, the battery can be positioned on a sample pad 11, on a sink pad, at the backside of the microfluidic device, or in parallel thereof. Following table describes the pros and cons of each configuration.

TABLE-US-00001 TABLE 1 Examples of battery configurations Position of battery PROS CONS Sample Energy from the battery is The by-products of the pad produced from the moment the battery reaction might liquid sample is added. affect the operation of the assay. Sink pad By-products of battery reaction The flow rate of sample in do not affect the assay. the battery and the filling The battery can provide a time is limited by the assay signal of the moment when the membrane materials. liquid sample has reached the pad. Easy to include in the assay. Backside Does not interfere with the It may be more expensive assay. to integrate. It can be fabricated independently of the assay and combined during final assembly. The battery can take advantage of the whole length of the assay. Parallel Battery is fabricated completely The battery has to be independent from the assay. connected to the assay The battery can be fabricated afterwards which may lead with less design restrictions. to higher production costs.

[0051] Delivery energy time interval t.sub.operation of the battery 12 can be modified using several strategies, alone or in combination, for example: [0052] By means of an electric discharge load. The value of the electrical passive (like a resistor) or active load (like a circuit or other elements) applied to the battery 12 determines the electric current and, therefore, the rate of discharge of the battery 12. The discharge curve of the battery 12 will be affected by the value of the discharge load, so that the discharge time of the battery 12 is reduced by decreasing the nominal value of the discharge load (or increasing high currents). [0053] Modifying the active area of the battery 12. The amount of electrical current that a battery can produce is proportional to its active area (anode and cathode area). Therefore, increasing the electrode area increases the discharge time of the battery 12 working under the same resistance value. [0054] Modifying the anode thickness of the battery 12. The amount of anode material, which is the material that is consumed during the electrochemical reaction, will determine the operation time of the battery 12. Once the anode is consumed, the battery 12 stops working. The higher the thickness of the anode, the more available material to be consumed and, therefore, the longer discharge times of the batteries.

[0055] To control more precisely operation time of the battery 12, an electrical circuit, e.g. electrical switches using transistors or operational amplifiers (not shown), can be used as a switch to start or terminate the delivering of power (electric charge) when the battery 12 reaches a given voltage or current level.

[0056] With reference to FIG. 5, therein it is illustrated an embodiment in which the auxiliary device 16 comprises a lighting system such as a LED. The LED can be used to help the user of an assay to know the period when the test is valid to be read. The LED would indicate the user of the test to read the results after the LED has switched off. That is, in this example, the LED would only be ON during the t.sub.operation period of the battery 12. Alternatively, the auxiliary device 16 can comprise an audible system such as a loudspeaker, a buzzer or an alarm, and/or a device transmitting a radiofrequency signal.

[0057] In another embodiment, the electrical energy provided by the battery 12 can be used to power a window as auxiliary device 16. The window can be maintained closed and only be opened when the result of the test is valid (adjusting t.sub.operation to this valid time range). The window can be a mechanical window, a liquid crystal dispersion film, electrochromic film or any other.

[0058] In yet another embodiment, the electrical energy provided by the battery 12 can be used to generate heat by means of a heater as auxiliary device 16. The heater would behave as a resistive load connected to the battery 12, which contributes to the battery discharging. Therefore, the battery operation time and heater temperature would need to be properly adjusted. The heater temperature could be predefined during device design and fabrication using technologies such as positive temperature coefficient (PTC) heaters. Another way to control the temperature is combining the heater with a phase change material, which is capable of storing a large amount of thermal energy, sustaining a predefined temperature before melting. This particular embodiment can be of great importance in the lateral flow industry as in this industry there is a need to heat up the test to 37° C. in order to improve test reproducibility and to enhance its sensitivity. The heater could also be used to perform other functions in the test, such as cellular lysis or nucleic acid amplification.

[0059] With reference now to FIG. 6, the microfluidic device is arranged inside a casing 1, or cassette, to provide robustness and facilitate addition of the liquid sample and reading of the result. The casing 1 can be made of plastic or other materials such as a polymeric material or a wax.

[0060] The casing 1 can incorporate some or all of the components involved in the present invention, such as the battery 12, auxiliary device 16, conducting tracks 14, an electrical discharge load 15. Some of these components could be fabricated using manufacturing technologies such as 3D electronics, printed thermoformed electronics, among others.

[0061] It should be apparent to those skilled in the art that the description and figures are merely illustrative and not limiting. They are presented by way of example only.

[0062] The scope of the present invention is defined in the following set of claims.