Precise Fluid Dosing Control for Point-of-Care Devices

Abstract

Devices and methods for controlling collection of liquid samples are described. In one example, a microfluidic device may include an analytical device and an actuator. The actuator is connectable to the analytical device. The actuator may be operable to absorb fluid. The actuator may direct the absorbed fluid to an input layer of the analytical device. The actuator may deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device.

Description

[Technical Field]

[0001] FIELD OF THE DISCLOSURE The present disclosure relates generally to paper-based microfluidic devices and methods for autonomous sample collection with paper-based microfluidic devices. [Background technology]

[0002] Paper-based microfluidic devices may require precise control of the volume of input sample or buffer. Inaccurate volumes of input sample can lead to reduced accuracy and increased erroneous results. Although external tools such as pipettes can be used to deliver measured volumes of input sample, measurements from such external tools can be prone to error, especially for small sample volumes (e.g., in the microliter range). Laboratory-grade external tools, such as laboratory-grade pipettes, can be expensive and may not be suitable for applications such as point-of-care (PoC) applications. Summary of the Invention

[0003] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device.

[0004] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material and a second layer of a second material having different swelling ratios.

[0005] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material and a second layer of a second material having different swelling ratios. The first material can be paper and the second material can be polypropylene.

[0006] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The absorption condition can include the actuator absorbing the fluid for a predetermined time.

[0007] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The absorption condition can include the actuator absorbing fluid for a predetermined time. The amount of fluid collected by the analytical device can be based on the predetermined time.

[0008] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The analytical device can be a microfluidic paper-based analysis device (μPAD).

[0009] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material, a second layer of a second material, and a third layer of a third material. The first and second materials can have different swelling ratios, and the third material can be a conductive material.

[0010] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material, a second layer of a second material, and a third layer of a third material. The first and second materials can have different swelling ratios, and the third material can be a conductive material. The layer of conductive material can be one of silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS).

[0011] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The absorption condition can be the application of a predetermined amount of voltage to the actuator through a third layer of material.

[0012] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The absorption condition can be application of a predetermined amount of voltage to the actuator through a third layer of material. The amount of fluid collected by the analytical device can be based on the predetermined amount of voltage.

[0013] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connected to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device.

[0014] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connected to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material and a second layer of a second material having different swelling ratios.

[0015] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material and a second layer of a second material having different swelling ratios. The first material can be paper, and the second material can be polypropylene.

[0016] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. Setting the absorption condition can include setting a predetermined time for the actuator to absorb the amount of fluid.

[0017] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The analytical device can be a microfluidic paper-based analytical device (μPAD).

[0018] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator is connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material, a second layer of a second material, and a third layer of a third material. The first and second materials can have different swelling ratios, and the third material can be a conductive material.

[0019] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator is connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material, a second layer of a second material, and a third layer of a third material. The first and second materials can have different swelling ratios, and the third material can be a conductive material. The conductive material layer can be one of silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS).

[0020] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator is connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. Setting the absorption condition can include setting a predetermined amount of voltage to be applied to the actuator through a third layer of material in response to immersion of the actuator in the fluid pool.

[0021] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third substrate layer including a flow-directing element with a fourth substrate layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool.

[0022] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third substrate layer including a flow-directing element with a fourth substrate layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The injection layer can be formed by combining the first layer and the second layer with a layer of conductive material.

[0023] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The injection layer can be formed by combining the first and second layers with a layer of conductive material, which can be one of silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS).

[0024] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The first material and the second material can have different swelling ratios.

[0025] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The first material may be paper and the second material may be polypropylene.

[0026] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The first and second substrates may be comprised of paper and wax.

[0027] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The analytical device may be a microfluidic paper-based analytical device (μPAD).

[0028] Further features, as well as the structure and operation of various embodiments, are described in detail below with reference to the accompanying drawings, where like reference numbers indicate identical or functionally similar elements. [Brief explanation of the drawings]

[0029] [Figure 1A] FIG. 1 illustrates an exemplary implementation of precision fluid input control for a point-of-care device in one embodiment. [Figure 1B] FIG. 10 illustrates another exemplary implementation of precision fluid input control for a point-of-care device in one embodiment. [Figure 2] FIG. 2 is a diagram illustrating details of an actuator according to an embodiment. [Figure 3A]1A-1D illustrate manufacturing steps for fabricating a microfluidic device according to one embodiment of the present disclosure. [Figure 3B] FIG. 10 illustrates additional manufacturing steps for fabricating a microfluidic device according to one embodiment of the present disclosure. [Figure 3C] FIG. 1 illustrates, in one embodiment, multiple layers of a microfluidic device according to the present disclosure. [Figure 4] FIG. 10 illustrates another exemplary implementation of precision fluid input control for a point-of-care device in one embodiment. [Figure 5] FIG. 10 illustrates details of another actuator in one embodiment. [Figure 6A] 1A-1C illustrate manufacturing steps for fabricating another microfluidic device according to the present disclosure, in one embodiment. [Figure 6B] FIG. 10 illustrates additional manufacturing steps for fabricating another microfluidic device according to the present disclosure, in one embodiment. [Figure 6C] FIG. 10 illustrates additional manufacturing steps for fabricating another microfluidic device according to the present disclosure, in one embodiment. [Figure 6D] FIG. 10 illustrates additional manufacturing steps for fabricating another microfluidic device according to the present disclosure, in one embodiment. [Figure 6E] FIG. 1 illustrates, in one embodiment, multiple layers of another microfluidic device according to the present disclosure. [Figure 7] 1 is a flow diagram illustrating a process for implementing precision fluid input control of a point-of-care device in one embodiment. [Figure 8] 1 is a flow diagram illustrating a process for forming a microfluidic device in one embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0030] In some examples, point-of-care applications may involve lateral flow assays with samples and reagents on the order of microvolume, such as sample deposition of approximately 10 microliters (μL) of blood and reagent pipetting of approximately 100 μL of saline. In one example, disposable plastic pipettes can be used in a variety of applications and may be inexpensive tools, but disposable plastic pipettes generally have low metering accuracy (e.g., accuracy may be in the milliliter (mL) range at best). In another example, laboratory-grade microliter pipettes can provide sample volume accuracy but may be prohibitively expensive and unsuitable for point-of-care applications. For example, such laboratory-grade pipettes may not meet the World Health Organization's ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free and Deliverable to end-users) criteria for diagnostic testing applications in resource-constrained countries.

[0031] The devices, systems, and methods described herein can provide an autonomous approach to precisely sample collection for microfluidic devices. This approach involves utilizing a mechanism to self-limit fluid input. This approach can also improve the convenience and accuracy of microfluidic devices in point-of-care applications by eliminating the need for external tools, reducing testing costs and test kit complexity / volume. The devices, systems, and methods described herein can achieve relatively high precision, such as in the microliter range, of fluid or liquid inputs (e.g., sample or buffer) for point-of-care or microfluidic applications without the need for expensive metering control tools. Furthermore, the structures described herein can be constructed from materials carefully selected to achieve this autonomous approach and precision, thus providing a reliable and reproducible approach to limiting the amount of liquid or fluid input into point-of-care or microfluidic devices. Some applications may also require colorimetric reactions, which may require reproducible ratios of reagents and sample to obtain consistent results. The devices, systems, and methods described herein can provide a method for reproducible ratios of reagents and samples to obtain consistent results without the need for expensive tools such as laboratory-grade pipettes, and without relying on the manual control of external tools or the operator's manual ability.

[0032] In some examples, an apparatus for controlling the collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The deformation of the actuator can result in precise and autonomous collection of sample fluid for the analytical device.

[0033] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material and a second layer of a second material having different swelling ratios. The first and second layers having different swelling ratios can facilitate the deformation of the actuator. The deformation of the actuator can result in precise and autonomous collection of sample fluid for the analytical device.

[0034] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material and a second layer of a second material having different swelling ratios. The first material can be paper, and the second material can be polypropylene. Materials such as paper and polypropylene can be readily available and relatively inexpensive materials.

[0035] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The absorption condition can include the actuator absorbing the fluid for a predetermined time. The predetermined time can allow the actuator to autonomously contract once sufficient sample fluid has been collected by the analytical device.

[0036] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The absorption condition can include the actuator absorbing fluid for a predetermined time. The amount of fluid collected by the analytical device can be based on the predetermined time. The amount of fluid collected by the analytical device can be relatively easily controlled by controlling the predetermined time.

[0037] In some examples, an apparatus for controlling the collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The analytical device can be a microfluidic paper-based analytical device (μPAD). Analytical devices such as μPADs can be portable and affordable in cost.

[0038] In some examples, an apparatus for controlling the collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material, a second layer of a second material, and a third layer of a third material. The first and second materials can have different swelling ratios, and the third material can be a conductive material. The first and second layers having different swelling ratios can facilitate deformation of the actuator. Deformation of the actuator can result in precise and autonomous collection of sample fluid for the analytical device. The third layer of conductive material can facilitate application of an external stimulus that deforms the actuator.

[0039] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material, a second layer of a second material, and a third layer of a third material. The first and second materials can have different swelling ratios, and the third material can be a conductive material. The conductive material layer can be one of silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). These conductive materials can be readily available.

[0040] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The absorption condition can be the application of a predetermined amount of voltage to the actuator through a third layer of material. The predetermined amount of voltage can enable the actuator to autonomously contract when sufficient sample fluid has been collected by the analytical device.

[0041] In some examples, an apparatus for controlling collection of a liquid sample is outlined. The apparatus can include an analytical device and an actuator. The actuator can be connectable to the analytical device. The actuator can be operable to absorb a fluid. The actuator can direct the absorbed fluid to an input layer of the analytical device. The actuator can deform in response to the occurrence of an absorption condition. The degree of deformation of the actuator indicates the amount of fluid collected by the analytical device. The absorption condition can be application of a predetermined amount of voltage to the actuator through a third layer of material. The amount of fluid collected by the analytical device can be based on the predetermined amount of voltage. The amount of fluid collected by the analytical device can be relatively easily controlled by controlling the predetermined amount of voltage.

[0042] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connected to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The deformation of the actuator can result in precise and autonomous collection of sample fluid for the analytical device.

[0043] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connected to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material and a second layer of a second material having different swelling ratios. The first and second layers having different swelling ratios can facilitate deformation of the actuator. Deformation of the actuator can result in precise and autonomous collection of sample fluid for the analytical device.

[0044] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material and a second layer of a second material having different swelling ratios. The first material can be paper, and the second material can be polypropylene. Materials such as paper and polypropylene can be readily available and relatively inexpensive.

[0045] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. Setting the absorption condition can include setting a predetermined time for the actuator to absorb the amount of fluid. The predetermined time can allow the actuator to autonomously contract once sufficient sample fluid has been collected by the analytical device. The amount of fluid collected by the analytical device can be relatively easily controlled by controlling the predetermined time.

[0046] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The analytical device can be a microfluidic paper-based analytical device (μPAD). Analytical devices such as μPADs can be portable and affordable.

[0047] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connected to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material, a second layer of a second material, and a third layer of a third material. The first and second materials can have different swelling ratios, and the third material can be a conductive material. The first and second layers having different swelling ratios can facilitate deformation of the actuator. Deformation of the actuator can result in precise and autonomous collection of sample fluid for the analytical device. The third layer of conductive material can facilitate application of an external stimulus to deform the actuator.

[0048] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator is connectable to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. The actuator can include a first layer of a first material, a second layer of a second material, and a third layer of a third material. The first and second materials can have different swelling ratios, and the third material can be a conductive material. The conductive material layer can be one of silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). These conductive materials can be readily available.

[0049] In some examples, a method for controlling the amount of fluid collected by an analytical device is outlined. The method can include immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator. The actuator can be connected to an analytical device of the microfluidic device. The method can further include setting an absorption condition to control the amount of fluid collected by the analytical device. The actuator can deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator can indicate the amount of fluid collected by the analytical device. Setting the absorption condition can include setting a predetermined amount of voltage to be applied to the actuator through a third layer of material in response to immersion of the actuator in the fluid pool. The predetermined amount of voltage can allow the actuator to autonomously contract when sufficient sample fluid is collected by the analytical device. The amount of fluid collected by the analytical device can be relatively easily controlled by controlling the predetermined amount of voltage.

[0050] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. Deformation of the actuator can result in precise and autonomous collection of sample fluid for an analytical device.

[0051] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The input layer can be formed by combining the first and second layers with a layer of conductive material. A third layer of conductive material can facilitate application of an external stimulus to deform the actuator.

[0052] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The injection layer can be formed by combining the first and second layers with a layer of conductive material, which can be one of silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene)polystyrenesulfonate (PEDOT:PSS). These conductive materials can be readily available.

[0053] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The first and second materials can have different swelling ratios. The first and second layers having different swelling ratios can facilitate deformation of the actuator. The deformation of the actuator can result in precise, autonomous collection of sample fluid for an analytical device.

[0054] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The first material can be paper and the second material can be polypropylene. Materials such as paper and polypropylene can be readily available and can be relatively inexpensive materials.

[0055] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The first and second substrates can be made of paper and wax. Materials such as paper and wax can be readily available and can be relatively inexpensive materials.

[0056] In some examples, a method for forming a microfluidic device is outlined. The method can include forming an input layer by bonding a first layer including a first substrate and a first actuator layer with a second layer including a second substrate and a second actuator layer. The first actuator layer can extend a specific length from an edge of the first substrate. The first actuator layer can be made of a first material. The second actuator layer can extend a specific length from an edge of the second substrate. The second actuator layer can be made of a second material different from the first material. The method can further include forming a reaction layer by bonding a third layer including a flow-directing element with a fourth layer including at least one reaction chamber. The method can further include bonding the input layer and the reaction layer to form a microfluidic device. The formed microfluidic device can include an analytical device and an actuator. The actuator can include a first actuator layer and a second actuator layer. The actuator can deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool. The analytical device can be a microfluidic paper-based analytical device (μPAD). Analytical devices such as μPADs can be portable and affordable in cost.

[0057] FIG. 1A illustrates an exemplary implementation of precision fluid input control for a point-of-care device in one embodiment. In the example shown in FIG. 1A, an apparatus or microfluidic device 110 can include an analytical device 111 and an actuator 112. The microfluidic device 110 can be a paper-based microfluidic device including multiple paper substrates arranged in layers (e.g., stacked), where each layer of the paper substrate can be manufactured with a different material, region, or pattern, or a combination thereof. The analytical device 111 can be, for example, a microfluidic paper-based analytical device (μPAD). In some examples, the paper substrates arranged to form the analytical device 111 can include chromatography paper, filter paper, wax-patterned paper, or other types of paper substrates, or a combination thereof. The analytical device 111 can include a microfluidic mesh material capable of transporting, mixing, separating, or processing fluids based on fluid control using, for example, capillary forces.

[0058] The actuator 112 can be a paper-based actuator (e.g., made of paper). The actuator 112 can also be a paper-based bilayer actuator including two layers of materials with different swelling rates (e.g., moisture shrinkage / swelling coefficients). In some examples, the bilayer material can be paper and polypropylene. Other examples of materials from which the actuator 112 can be constructed include, but are not limited to, paper with graphene oxide or polydimethylsiloxane (PDMS), nanoporous gold with polyaniline, parafilm with a carbon nanotube sheet bonded with polyimide or polydimethylsiloxane, or other types of materials or combinations thereof. The bilayer materials with different swelling rates can cause a portion of the actuator 112 to deform (e.g., contract, bend, curve, or other types of deformation, or a combination thereof) in response to the actuator 112 picking up or absorbing a specific amount of fluid. For example, as shown in FIG. 1A, the actuator 112 of the microfluidic device 110 can be immersed (or submerged, or dipped, or have one edge contacting) a liquid pool 120. The liquid pool 120 can be any type of fluid or liquid depending, for example, on the desired application of the microfluidic device 110. In response to immersion of a portion of the actuator 112 in the liquid 120, a condition 125, such as the application of one or more external stimuli, can trigger deformation of the actuator 112.

[0059] In a first exemplary embodiment, the actuator 112 can be a wet-activated bilayer sample collection element including an active layer (e.g., paper) and a passive layer or substrate (e.g., polypropylene). In the first exemplary embodiment, the condition 125 can be exposure to wetness (e.g., an external stimulus). Exposure to wetness can occur, for example, by immersing the actuator 112 in a liquid pool 120 for a predetermined or specific time period. The actuator 112 can absorb a certain amount V of liquid 120 within the predetermined time period and gradually transform into the structure 114. In one example, the amount V can be a portion of the liquid pool 120. In the first exemplary embodiment, because the paper layer has a higher coefficient of hygroscopic expansion than the polypropylene layer, the paper active layer can swell and increase in size significantly more than the polypropylene passive layer. The difference in the coefficients of hygroscopic expansion of the two layers can cause the actuator 112 to deform in response to the external stimulus of wetness (e.g., once a sufficient amount V of liquid has been absorbed).

[0060] In a second exemplary embodiment, the actuator 112 can be a thermoelectrically activated bilayer sample collection element including two active layers (e.g., paper and polypropylene). One of the two active layers (e.g., the polypropylene layer) can have a higher thermal expansion coefficient, and the other active layer (e.g., the paper layer) can have a higher hygroscopic expansion coefficient. In the second exemplary embodiment, the actuator 112 can further include a layer of electrodes (e.g., silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene)polystyrenesulfonate (PEDOT:PSS)). In the second exemplary embodiment, the condition 125 can be an electrically induced temperature change (e.g., heat) and / or exposure to moisture. The electrically induced expansion of the active layer with the higher thermal expansion coefficient (e.g., the polypropylene layer) can be stronger than the moisture-induced expansion of the layer with the lower thermal expansion coefficient (e.g., the paper layer), thus deforming the entire actuator structure 114. An electrically induced temperature change can be induced, for example, by applying a voltage to electrodes integrated into actuator 112 to heat actuator 112. An active layer of actuator 112, having a different, higher coefficient of thermal expansion, can deform into structure 114 in response to a temperature change while absorbing fluid in an amount V that depends on the time the actuator is immersed in the liquid. FIG. 1A includes a side perspective view 130 of microfluidic device 110, including analytical device 111 and structure 114.

[0061] The deformation of the structure 114 of the actuator 112 can indicate the amount of liquid absorbed by the actuator 112. Therefore, by selecting materials with different swelling ratios to construct the actuator 112 and choosing one of 1) a specific time for which the actuator 112 is immersed in the liquid 120, and 2) the application of a specific voltage to the actuator, a precise amount of liquid 120 can be collected by the actuator 112. The amount V of liquid 120 collected by the actuator 112 can be directed or flowed to an input layer of the analytical device 111 for further processing and analysis. In some examples, a portion of the amount V of liquid 120 absorbed by the actuator 112 can be directed or flowed to an input layer of the analytical device 111, and the remaining portion of the amount V of liquid 120 can remain in the actuator 112.

[0062] Additionally, the transformation of actuator 112 into structure 114 may cause the material of actuator 112 to bend or lift away from liquid 120, such that the material of actuator 112 can no longer contact liquid 120. In the example shown in FIG. 1B , actuator 112 may be immersed in liquid 120. After a time t1, actuator 112 may autonomously transform into structure 113, and the degree of transformation from actuator 112 to structure 113 may indicate a first amount of liquid 120 absorbed by actuator 112. Note that structure 113 may still be immersed in liquid 120. However, after a further time, such as t2, structure 113 may autonomously transform into structure 114, such that structure 114 is no longer immersed in liquid 120. The degree of transformation of actuator 112 into structure 114 after time t1+t2 can indicate the total amount of liquid 120 (e.g., amount V) absorbed by actuator 112, where the second amount can be greater than the first amount. Thus, the transformation of actuator 112 into structure 114 can be autonomous such that external tools and / or manual control for precise collection of the liquid sample can be obviated.

[0063] FIG. 2 illustrates details of an actuator (e.g., actuator 112 of FIGS. 1A and 1B ) in one embodiment. In the illustrated embodiment, actuator 112 can include a first layer 210 and a second layer 220. First layer 210 and second layer 220 can be made of different materials, such as materials with different swelling ratios. For example, first layer 210 can be made of chromatography paper, and second layer 220 can be made of polypropylene. In some illustrated embodiments, second layer 220 can be made of adhesive polypropylene. First layer 210 can have a width w1 and a height h1+h2. Second layer 220 can include a first portion 221 having a width w1 and a height h2, and a second portion 222 having a width w1+w2+w2 and a height h1. In the example shown in FIG. 2, the actuator 112 can be a wet-activated bilayer sample collection element including an active layer (e.g., layer 210) and a substrate or passive layer (e.g., layer 220). An example of an active layer can be, for example, a layer of material that can respond (e.g., contract or expand) to an external stimulus (e.g., absorption of a liquid or fluid). The deformation of the actuator 112 in response to wetting or fluid absorption can be the result of the reaction of the active layer to the wetting or fluid absorption. The substrate layer of the bilayer actuator may not respond to the external stimulus. The reaction (e.g., contraction or expansion) by the active layer and the lack of reaction by the substrate layer can cause the actuator 112 to deform or contract. In the example of FIG. 2, the relatively higher hygroscopic swelling coefficient of the paper material can cause the paper layer to expand upon absorption of a liquid, while the relatively lower hygroscopic swelling of the polypropylene material can cause little change or deformation, ultimately causing the actuator 112 to deform into structure 114, as shown in FIG. 1B.

[0064] The first layer 210 can have a thickness d1, and the second layer 220 can have a thickness d2. The thicknesses of the first layer 210 and the second layer 220 can be the same or different. For example, d1 can be 0.18 millimeters (mm) and d2 can be 0.3 mm. The absorbency of the actuator 112 can also be based on the materials and thicknesses of the first layer 210 and the second layer 220. For example, if the first layer 210 is chromatography paper with a thickness d1=0.18 mm and the second layer 220 is polypropylene with a thickness d2=0.3 mm, the actuator 112 can absorb the liquid 120 in a volume of 1 square millimeter (mm). 2 ) and may take about 120 seconds to collect or absorb about 100 μL of liquid 120.

[0065] FIG. 3A illustrates manufacturing steps for fabricating a microfluidic device according to one embodiment of the present disclosure. In the example shown in FIG. 3A, a first actuator layer 310 can be attached to a substrate layer 302 of an analytical device 111. The first actuator layer 310 can include a portion 311, which can overlap a portion of the substrate layer 302 of the analytical device 111, as shown in cross section 307 in FIG. 3A. In one example, the first actuator layer 310 can be made of paper. The first actuator layer 310 can be one layer (e.g., an active layer) of a wet-activated bi-layer actuator, such as the actuator 112 shown in FIGS. 1A-2. In one example, the substrate layer 302 can be a paper-based device with wax-printed defining structures.

[0066] A mask 304 can be overlaid on a portion of the substrate layer 302 and the first actuator layer 310. In the example shown in FIG. 3 , the mask 304 can be overlaid on the rear or backside 303 of the substrate layer 302. In one example, the mask 304 can be masking tape or a hard mask and can be made of materials such as plastic, glass, metal, or other types of materials, or combinations thereof. The mask 304 can include holes, any geometric shape, or openings 306. The openings 306 can have the same shape as the first actuator layer 310 so that the first actuator layer 310 can fit into the openings 306 when the mask 304 is overlaid on the backside 303 of the substrate layer 302 and the first actuator layer 310. The openings 306 can include a portion 305 that can overlap the backside 303 of the substrate 302, and this portion 305 can have the same shape as or a different shape from the portion 311 of the actuator layer 310. The thickness of the first actuator layer 310 may be less than, greater than, or equal to the thickness of the substrate layer 302. The mask 304 may cover a portion of the back surface 303 of the substrate layer 302, as shown by cross section 309.

[0067] FIG. 3B illustrates additional manufacturing steps for fabricating a microfluidic device according to one embodiment of the present disclosure. The additional manufacturing steps illustrated in FIG. 3B can be a continuation of the manufacturing steps illustrated in FIG. 3A. In the example illustrated in FIG. 3B, in response to superimposing a mask 304 on the first actuator layer 310 and the backside 303 of the substrate layer 302, a layer of material 314 can be applied over the first actuator layer 310 and a portion of the mask 304. Material 314 can be, for example, polypropylene. Material 314 can be applied over the entire first actuator layer 310 and a portion of the mask 304, as illustrated in cross section 317 of FIG. 3B. Note that in the example illustrated in cross section 317, the thickness of material 314 can be greater than the thickness of the actuator layer 310. However, the thicknesses of material 314 and first actuator layer 310 can be any desired thickness. The thickness of mask 304 can be the same as the desired thickness of material 314, depending on the technique used to deposit material 314. For example, if a silkscreening method is used, the mask 304 must have the same thickness as the material 314. On the other hand, if the material 314 is sprayed, the mask 304 does not need to have the same thickness as the material 314. The material 314 can be a material used to form another actuator layer (e.g., a passive layer) of a wet-activated bilayer actuator, such as the actuator 112 shown in FIGS. 1A-2. For example, the material 314 can be polypropylene, which can be used to form the second layer 220 shown in FIG. 2. The material 314 can also include an adhesive material so that when the material 314 is placed on the first actuator layer 310 and the mask 304, the material 314 can be attached to the first actuator layer 310 and the mask 304. The area of ​​the material 314 does not need to be larger than the area of ​​the mask 304 to prevent the material 314 from adhering to the back surface 303 of the substrate 302.

[0068] In response to disposing the material 314 over the first actuator layer 310 and the mask 304, the mask 304 can be removed. Removing the mask 304 can include removing the portion of the mask 304 that is affixed with the material 314. In response to removing the mask 304 and the material 314 affixed to the mask 304, a second actuator layer (e.g., second layer 220 shown in FIG. 2 ) having the material 314 of a bi-layer actuator can be formed. The resulting structure 316 can include the second actuator layer of material 314 and the first actuator layer 310, as shown in cross section 318.

[0069] 3C illustrates multiple layers of a microfluidic device according to one embodiment of the present disclosure. In the example shown in FIG. 3C, the back surface 303 of the substrate 302 and the material layer 314 of the structure 316 can form a first layer 320 of the microfluidic device 110. The layer 314 of the structure 316 can be a layer of the actuator 112, and the back surface 303 of the substrate 302 can be a layer of the analytical device 111. The structure 316 can have a width w1, and the portion of the substrate 316 corresponding to the first actuator layer 310 can extend from the substrate 302 by approximately a height or length h2.

[0070] In the example shown in FIG. 3C, substrate 302 and substrate 334 can form second layer 321 of microfluidic device 110. Substrate 302 can be a paper-based layer with a wax-printed geometric shape. Substrate 334 can include portion 335 having width w1, and portion 335 of substrate 334 can extend from substrate 302 by approximately length h2. Substrate 334 can further include a portion incorporated into substrate 302 corresponding to portion 311 in FIG. 3A. In one example, the shape on substrate 302 can be patterned by applying wax to paper-based substrate layer 334 and leaving the remaining paper area 334 uncovered by wax. Substrate 334 can be, for example, a paper substrate. Extended portion 335 of substrate 334 can form first actuator layer 310 of actuator 112. The first layer 320 and the second layer 321 can be joined (e.g., patterned on opposite sides of the same paper-based substrate or from two separate paper-based substrates that are superimposed) to form an input structure of the microfluidic device 110, where the input structure can collect a liquid or fluid flowing from the actuator 112. The input structure formed by the first layer 320 and the second layer 321 can include the actuator 112. In one example, a liquid sample collected or absorbed by the actuator 112 can be absorbed in a direction 336 toward a portion of the substrate 334 located within the substrate 302. The substrate 334 can also include a foldable edge 332 to prevent deformation of the actuator 112 from deforming the substrate 302.

[0071] In the example shown in FIG. 3C , the third layer 322 can include a substrate 340, which can include a directing element 342. The substrate 340 can be a paper-based layer with wax-printed geometries. The directing element 342 can be etched or patterned into the substrate 340. In some examples, techniques such as inkjet etching, inkjet printing, wax printing, laser printing, lithography, three-dimensional (3D) printing, or other types of etching, patterning, or fabrication techniques, or combinations thereof, can be used to form the substrate 340 and the directing element 342 of the third layer 322. The third layer 322 can be a layer of the analytical device 111. A liquid sample collected or absorbed by a substrate 334 located within the substrate 302 can be collected by the directing element 342 in response to bonding the third layer 322 to the second layer 321.

[0072] In the example shown in FIG. 3C , the fourth layer 323 can include a substrate 350, which can include one or more reaction chambers 352. The substrate 350 can be a paper-based layer with a wax-printed structure. The reaction chambers 352 can be etched or patterned into the substrate 350. In some examples, techniques such as inkjet etching, inkjet printing, wax printing, laser printing, lithography, three-dimensional (3D) printing, or other types of etching, patterning, or fabrication techniques, or combinations thereof, can be used to form the substrate 350 and the reaction chambers 352 of the fourth layer 323. The fourth layer 323 can be a layer of the analytical device 111. A liquid sample collected or absorbed by the flow-directing element 342 of the third layer 322 can be flowed into the reaction chambers 352 in response to binding of the third layer 322 to the fourth layer 323. The third layer 322 and the fourth layer 323 can be joined (e.g., stacked) to form a reaction layer of the microfluidic device 110. In one example, a different chemical reagent can be disposed in each of the reaction chambers 352. A liquid sample collected by the actuator 112 can be directed into the reaction chambers 352, and chemical reactions can occur between the collected sample and different reagents in the different reaction chambers. In some examples, the chemical reactions can be visible through the reaction chambers 352 via colorimetric or fluorescent reactions.

[0073] The first layer 320, the second layer 321, the third layer 322, and the fourth layer 323 can be bonded (e.g., stacked) to form the microfluidic device 110. In response to bonding the first layer 320, the second layer 321, the third layer 322, and the fourth layer 323, an actuator 112 can be formed, and the actuator 112 can extend from an edge of the analytical device 111. In one example, the order of bonding or stacking the various layers shown in FIG. 3C can be the first layer 320, the second layer 321, the third layer 322, and the fourth layer 323. In one example, the first layer 320 and the second layer 321 can be opposite sides of the same substrate layer. In one example, the first layer 320 can be stacked on top of the second layer 321 such that the back surface 303 of the substrate layer can cover a portion of the substrate 334 located within the substrate 302. In one example, second layer 321 can be stacked on top of third layer 322 such that backside 303 of substrate layer 302 covers flow direction elements 342 of substrate 340. The combination of second layer 321 and third layer 322 allows sample liquid collected at substrate 334 to be absorbed or collected by flow direction elements 342 of third layer 322. In one example, third layer 322 can be stacked on top of fourth layer 323 such that substrate 340 covers reaction chamber 352 of substrate 350. While four layers are shown in the example of FIG. 3C , one skilled in the art will recognize that a different number of layers can be used to form microfluidic device 110.

[0074] FIG. 4 illustrates another exemplary implementation of precision fluid input control for a point-of-care device in one embodiment. In the example shown in FIG. 4, an apparatus or microfluidic device 410 can include an analytical device 411, an actuator 412, and an interface 415. The microfluidic device 410 can be a paper-based microfluidic device including multiple paper substrates arranged in layers (e.g., stacked), where each layer of the paper substrate can be manufactured with a different material, region, or pattern, or a combination thereof. The analytical device 411 can be, for example, a microfluidic paper-based analytical device (μPAD). In some examples, the paper substrates arranged to form the analytical device 411 can include chromatography paper, filter paper, or other types of paper substrates, or a combination thereof. The analytical device 411 can include a microfluidic mesh material capable of transporting, mixing, separating, or processing fluids based on fluid control using, for example, capillary forces.

[0075] The actuator 412 can be a paper-based actuator (e.g., made of paper). The actuator 412 can also be a paper-based bilayer actuator including two layers of materials with different swelling rates (e.g., moisture and / or thermal shrinkage coefficients). In some examples, the bilayer material can be paper and polypropylene. Other examples of materials from which the actuator 412 can be constructed include, but are not limited to, paper with graphene oxide or polydimethylsiloxane (PDMS), nanoporous gold with polyaniline, parafilm with carbon nanotube sheets bonded with polyimide or polydimethylsiloxane, or other types of materials or combinations thereof. The bilayer materials with different swelling rates can cause a portion of the actuator 412 to deform (e.g., contract, bend, curve, or other types of deformation, or a combination thereof) in response to the uptake or absorption of a specific amount of fluid by the actuator 412 and the application of a voltage at the interface 415 by the external voltage source 401. 4, an actuator 412 of a microfluidic device 410 can be immersed (or submerged or dipped) in a liquid pool 420 and connected to a voltage source 401. The liquid pool 420 can be any type of fluid or liquid depending on, for example, a desired application of the microfluidic device 410. In response to the immersion of a portion of the actuator 412 in the liquid 420 and a temperature change (e.g., a temperature increase) caused by the application of a voltage from the voltage source 401, deformation of the actuator 412 can occur.

[0076] In one example, actuator 412 can be a thermoelectrically activated bilayer sample collection element including two active layers (e.g., paper and polypropylene) and can include electrodes (e.g., silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene)polystyrenesulfonate (PEDOT:PSS)). Condition 425 can be the application of a voltage by voltage source 401 to electrodes integrated into actuator 412 via interface 415. The voltage supplied by voltage source 401 can produce an external stimulus (e.g., heat) to the two active layers of actuator 412, which can respond to the supplied voltage. Voltage source 401 can be, for example, a voltage generator, a computing device, a battery, a power bank, or any other type of electronic device capable of supplying a voltage to interface 415, or a combination thereof. Interface 415 may be a standard interface used in various electrical devices to improve end-user convenience, such as Universal Serial Bus (USB) and its derivatives (e.g., micro USB, mini USB, USB-C, etc.). Application of a voltage may deform actuator 412. Different amounts of voltage may cause different degrees of deformation. For example, application of voltage v1 may cause actuator 412 to deform into structure 413, and application of voltage v2 may cause actuator 412 to deform into structure 414.

[0077] The deformation of the actuator 412 to the structure 414 can control the amount of liquid absorbed by the actuator 412. Therefore, by selecting materials with different swelling and thermal expansion coefficients to construct the actuator 412 and setting a predetermined voltage applied to the actuator 412, a precise amount of liquid 420 can be drawn by the actuator 412. For example, application of a voltage v1 can cause the actuator 412 to deform the structure 413, while the structure 413 can remain immersed in the liquid 420. Increasing the voltage v1 to v2 can enable application of voltage v2 to the actuator 412, causing the actuator 412 to deform the structure 414. The deformation of the actuator 412 to the structure 414 can lift or bend the material of the actuator 412 away from the liquid 420, such that the material of the actuator 412 can no longer contact the liquid 420. The lack of contact between the structure 414 and the liquid 420 can determine when a desired amount of liquid 420 has been drawn by the microfluidic device 410. The amount of liquid 420 collected by the actuator 412 can be directed or flowed to an input layer of the analytical device 411 for further processing and analysis. The deformation of the actuator 412 to the structure 414 can be autonomous, so that external tools or manual control for precise collection of the liquid sample can be obviated. In some examples, a portion of the amount of liquid 420 absorbed by the actuator 412 can be directed or flowed to an input layer of the analytical device 411, and the remaining portion of the amount of liquid 420 can remain in the actuator 412.

[0078] FIG. 5 illustrates details of another actuator (e.g., actuator 412 of FIG. 4 ) in one embodiment. In the illustrated embodiment, actuator 412 can include a first layer 510, a second layer 520, and a third layer 521. First layer 510 and second layer 520 can be made of different materials, such as materials with different swelling and thermal expansion rates. For example, first layer 510 can be made of chromatography paper, and second layer 520 can be made of polypropylene. In some illustrated embodiments, second layer 520 can be made of adhesive polypropylene. First layer 510 and second layer 520 can have different shapes and dimensions (e.g., width and height or length) as shown in FIG. 5 . In the example shown in FIG. 5 , actuator 412 can be a thermoelectrically activated bilayer sample collection element including two active layers (e.g., layers 510 and 520) and can include a third layer of electrodes, such as third layer 521, that functions as a heating device. The third layer 521 can be made of a conductive material such as silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). The third layer 521 can be connected to the interface 415 via one or more contact terminals, such as contact terminals 522 and 523. The contact terminals 522 and 523 can be made of a conductive material such as silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS).

[0079] The first layer 510 can have a thickness d1, the second layer 520 can have a thickness d2, and the third layer 521 can have a thickness d3. The thicknesses of the first layer 510, the second layer 520, and the third layer 521 can be the same or different. For example, d1 can be 0.18 millimeters (mm), d2 can be 0.3 mm, and d3 can be approximately 50 nanometers (nm) to 100 nm. Additionally, the absorption coefficient of the actuator 412 can be based on the materials and thicknesses of the first layer 510, the second layer 520, and the third layer 521 and the voltage applied to the interface 415. For example, if the first layer 510 is chromatography paper with a thickness d1=0.18 mm, the second layer 520 is polypropylene with a thickness d2=0.3 mm, and the third layer 521 is AgNWs with a thickness of about 50 nm to 100 nm, the actuator 412 can absorb about 100 microliters (μL) with the application of a voltage of about 8 volts (V) to the interface 415.

[0080] FIG. 6A illustrates manufacturing steps for fabricating another microfluidic device according to the present disclosure in one embodiment. In the example shown in FIG. 6A, one actuator layer 610 can be attached to a substrate layer 602 of an analytical device 411. The actuator layer 610 can include a portion 611, which can overlap a portion of the substrate layer 602 of the analytical device, as shown in cross section 607 in FIG. 6A. In one example, the actuator layer 610 can be made of paper. The paper layer 610 can be one layer (e.g., an active layer) of the two-layer actuator 412 shown in FIGS. 4-5. In one example, the substrate layer 602 can be a paper-based layer with a wax-printed structure.

[0081] A mask 604 can overlay a portion of the substrate layer 602 and the actuator layer 610. The mask 604 can overlay the rear or backside surface 603 of the substrate layer 602. In one example, the mask 604 can be masking tape or a hard mask and can be made of materials such as plastic, glass, metal, or other types of materials, or combinations thereof. The mask 604 can include holes or openings 606. The openings 606 can have a different shape than the actuator layer 610. In the example shown in FIG. 6A , the openings 606 can be “U” shaped to correspond to the shape of the electrodes that provide uniform heating throughout the actuator 412. The openings 606 can have a portion 605 that overlaps the backside surface 603 of the substrate layer 602, and this portion 605 can have the same shape as or a different shape from the portion 611 of the actuator layer 610. The thickness of the actuator layer 610 can be thinner, thicker, or equal to the thickness of the mask 604. In some examples, the mask 604 can have different portions with different thicknesses. In one example, the mask 604 can cover a portion of the actuator layer 610, as shown in cross section 608. The mask 604 can also cover a portion of the back surface 603 of the substrate layer 602, as shown in cross section 609.

[0082] FIG. 6B illustrates additional manufacturing steps for fabricating another microfluidic device according to the present disclosure in one embodiment. The additional manufacturing steps illustrated in FIG. 6B may be a continuation of the manufacturing steps illustrated in FIG. 6A. In the example illustrated in FIG. 6B, in response to overlaying a mask 604 on the actuator layer 610 and the backside 603 of the substrate layer 602, a layer of material 614 may be disposed over the actuator layer 610 and a portion of the mask 604. Material 614 may be, for example, polypropylene. Material 614 may be disposed over a portion of the actuator layer 610 and a portion of the mask 604, as shown in cross section 617 in FIG. 6B. Material 614 may be a material used to form one layer (e.g., another active layer) of a bilayer actuator, such as actuator 412 illustrated in FIGS. 4-5. For example, material 614 may be polypropylene that may be used to form second layer 520 illustrated in FIG. 5. Additionally, material 614 may include an adhesive material such that when material 614 is placed on actuator layer 610 and mask 604, material 614 may be attached to actuator layer 610 and mask 604. Additionally, the area of ​​material 614 does not need to be larger than the area of ​​mask 604 to prevent material 614 from being attached to rear surface 603 of base layer 602.

[0083] In response to disposing the material 614 over the actuator layer 610 and the mask 604, the mask 604 can be removed. Removal of the mask 604 can include removing the portion of the mask 604 that is affixed with the material 614. In response to removing the mask 604 and the material 614 affixed to the mask 604, a second actuator layer 614 (e.g., second layer 520 shown in FIG. 5 ) of a bi-layer actuator can be formed. The resulting structure 616 can include the second actuator layer of material 614 and the first actuator layer 610, as shown in cross section 618.

[0084] FIG. 6C illustrates additional manufacturing steps for fabricating another microfluidic device according to the present disclosure in one embodiment. The additional manufacturing steps illustrated in FIG. 6C can be a continuation of the manufacturing steps illustrated in FIG. 6B. In the example illustrated in FIG. 6C, a mask 624 can overlay the back surface 603 of the substrate layer 602 and the layer of material 614 of the structure 616. In one example, the mask 624 can be masking tape or a hard mask and can be made of a material such as plastic, glass, metal, or other types of materials, or combinations thereof. The mask 624 can include a hole, any geometric shape, or an opening 626. The opening 626 can include a portion having the same shape as the opening 616 so that the structure 616 can fit within the opening 626 when the mask 624 is overlaid on the structure 616. The opening 626 can also include another portion having the shape of a contact terminal (e.g., contact terminals 522 and 523 shown in FIG. 5) that can be used to facilitate application of a voltage to a dual-layer actuator including the structure 616. In some examples, the mask 624 can have different portions with different thicknesses. Additionally, the mask 624 may cover the back surface 603 of the substrate layer 602 as shown in cross section 628 .

[0085] FIG. 6D illustrates additional fabrication steps for fabricating another microfluidic device according to the present disclosure in one embodiment. The additional fabrication steps illustrated in FIG. 6D can be a continuation of the fabrication steps illustrated in FIG. 6C. In the example illustrated in FIG. 6D, in response to superimposing a mask 624 over the backside 603 of the substrate layer 602 and the layer of material 614 of the structure 616, a layer of material 630 can be disposed over the mask 624. Material 630 can be disposed over a portion of the structure 616 (e.g., over material 614) and a portion of the mask 624, as shown by cross-section 638 in FIG. 6D. Material 630 can be a material used to form a layer of electrodes (e.g., third layer 521 shown in FIG. 5) on a bilayer actuator, such as actuator 412 shown in FIGS. 4-5. For example, material 630 can be silver nanowires (AgNWs) or a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS).

[0086] In response to disposing material 630 on mask 624, mask 624 can be removed. Removal of mask 624 can include removal of portions of mask 624 that are affixed with material 630. In response to removing mask 624 and material 630 affixed to mask 624, structure 636 (e.g., the combination of first layer 510, second layer 520, and third layer 521 shown in FIG. 5 ) of a two-layer actuator (e.g., actuator 412) can be formed. Structure 636 can include material 630, material 614, and first actuator layer 610, as shown in cross section 639.

[0087] 6E illustrates the layers of another microfluidic device according to one embodiment of the present disclosure. In the example shown in FIG. 6E, the back surface 603 of the substrate layer 602 and the structure 616 can form a first layer 640 of the microfluidic device 410. The structure 616 can be a layer of the actuator 412, and the back surface 603 of the substrate layer 602 can be a layer of the analytical device 411. The structure 616 can have a width w1, and a portion of the structure 616 can extend from the back surface 603 of the substrate layer 602 by approximately a height or length h2.

[0088] 6E, second layer 641 of microfluidic device 410 can be formed by a layer of material 630. Layer of material 630 can include contact terminals 631 and 632, which can connect layer 630 to interface 415 of microfluidic device 410.

[0089] In the example shown in FIG. 6E, the substrate layer 602 and the substrate 654 can form the third layer 642 of the microfluidic device 410. The substrate layer 602 can be a paper-based layer with wax-printed geometric shapes. The substrate 654 can be in contact with a portion 655 having a width w1, which corresponds to the first actuator layer 610 and can extend from the substrate 602 by approximately a length h2, such that the portion 611 of the first actuator layer overlaps the substrate 654. The substrate 654 can further include a portion integrated into the substrate layer 602. In one example, the shapes on the substrate layer 602 can be patterned by applying wax to the paper-based substrate layer 602 and leaving the remaining paper area 654 uncovered by the wax. The substrate 654 can be, for example, a paper substrate. The extended portion 655 of the substrate 654 can form the first layer of the actuator 412. The first layer 640, the second layer 641, and the third layer 642 can be combined (e.g., patterned on opposite sides of the same paper-based substrate or from two separate overlapping paper-based substrates) to form the input layer of the microfluidic device 410. The second layer 641 can be located between the first layer 640 and the third layer 642. The input layer formed by the first layer 640, the second layer 641, and the third layer 642 can include an actuator 412. In one example, a liquid sample collected or absorbed by the actuator 412 can be absorbed in a direction 656 into a portion of the substrate 654 located within the substrate layer 602. The substrate 654 can also include a foldable edge 652 to prevent deformation of the actuator 412 from deforming the substrate 602.

[0090] In the example shown in FIG. 6E, the fourth layer 643 can include a substrate 660, which can include a directing element 662. The substrate 660 can be a paper-based layer with wax-printed geometric shapes. The directing element 662 can be etched or patterned into the substrate 660. In some examples, techniques such as inkjet etching, inkjet printing, wax printing, laser printing, lithography, three-dimensional (3D) printing, or other types of etching, patterning, or fabrication techniques, or combinations thereof, can be used to form the substrate 660 and the directing element 662 of the fourth layer 643. The fourth layer 643 can be a layer of the analytical device 411. A liquid sample collected or absorbed by the substrate 654 located within the substrate layer 602 can be collected by the directing element 662 in response to binding of the fourth layer 643 to the third layer 642.

[0091] In the example shown in FIG. 6E , the fifth layer 644 can include a substrate 670, which can include one or more reaction chambers 672. The substrate 670 can be a paper-based layer with a wax-printed structure. The reaction chambers 672 can be etched or patterned into the substrate 670. In some examples, techniques such as inkjet etching, inkjet printing, wax printing, laser printing, lithography, three-dimensional (3D) printing, or other types of etching, patterning, or fabrication techniques, or combinations thereof, can be used to form the substrate 670 and the reaction chambers 672 of the fifth layer 644. The fifth layer 644 can be one layer of the analytical device 411. The fourth layer 643 and the fifth layer 644 can be combined (e.g., stacked on top of each other) to form a reaction layer of the microfluidic device 410. A liquid sample collected or absorbed by the directing element 662 of the fourth layer 643 can be distributed to the reaction chambers 672 in response to binding of the fourth layer 643 to the fifth layer 644. In one example, a different chemical reagent can be disposed in each of the reaction chambers 672. A liquid sample collected by the actuator 412 can be distributed to the reaction chambers 672, and chemical reactions can occur between the collected sample and different reagents in the different reaction chambers. In some examples, the chemical reactions can be visible through the reaction chambers 672.

[0092] The first layer 640, the second layer 641, the third layer 642, the fourth layer 643, and the fifth layer 644 can be bonded (e.g., stacked) together to form the microfluidic device 410. In response to bonding the first layer 640, the second layer 641, the third layer 642, the fourth layer 643, and the fifth layer 644, an actuator 412 can be formed and can extend from an edge of the analytical device 411. In one example, the order of bonding or stacking the various layers shown in FIG. 6E can be the first layer 640, the second layer 641, the third layer 642, the fourth layer 643, and the fifth layer 644. In one example, the first layer 640, the second layer 641, and the third layer 642 can be opposite sides of the same substrate layer. In one example, third layer 642 can be layered on fourth layer 643 such that substrate 602 can cover flow direction elements 662 of substrate 660. The combination of third layer 642 and fourth layer 643 allows sample liquid collected at substrate 654 to be absorbed or collected by flow direction elements 662 of fourth layer 643. In one example, fourth layer 643 can be layered on fifth layer 644 such that substrate 660 can cover reaction chamber 672 of substrate 670. While five layers are shown in the example of FIG. 6E , one skilled in the art will recognize that a different number of layers can be used to form microfluidic device 410.

[0093] The microfluidic devices described herein (e.g., microfluidic devices 110, 410) can provide precise liquid sample collection, e.g., in the microliter range, and the measurement of the amount of liquid sample collected can be autonomous. The actuators in the microfluidic devices described herein can be dual-layer actuators, where one layer can expand and the other layer can contract in response to an external stimulus, such as immersion in liquid for a period of time and / or application of a voltage. The contraction and expansion between the different layers can deform the actuator, and the degree of deformation can indicate the amount of liquid sample collected by the microfluidic device and / or the device heating time. Thus, by controlling the materials used to construct the actuator, the immersion time, and / or the applied voltage, the amount of sample liquid absorbed or collected can be precisely controlled.

[0094] 7 is a flow diagram illustrating a process 700 for implementing precision fluid injection control of a point-of-care device in one embodiment. Process 700 may include one or more operations, actions, or functions, as illustrated by one or more of blocks 702, 704, 706, or 708, or combinations thereof. Although illustrated as separate blocks, various blocks may be divided into further blocks, combined into fewer blocks, omitted, or performed in parallel, depending on the desired implementation.

[0095] Process 700 may begin at block 702. In block 702, an actuator of a microfluidic device may be immersed in a fluid pool to cause absorption of the fluid by the actuator. The actuator may be connectable to an analytical device of the microfluidic device. In some examples, the actuator may include a first layer of a first material and a second layer of a second material. The first material and the second material may have different swelling ratios. In some examples, the first material may be paper and the second material may be polypropylene. In some examples, the analytical device may be a paper-based analytical device (μPAD). In some examples, the actuator may further include a third layer of a third material. The third material may be a conductive material.

[0096] Process 700 may continue from block 702 to block 704. At block 704, an absorption condition may be established to control the amount of fluid collected by the analytical device. The actuator may deform in response to the occurrence of the absorption condition. The degree of deformation of the actuator may indicate the amount of fluid collected by the analytical device. In some examples, the absorption condition may be a predetermined time (block 706) for the actuator to absorb the amount of fluid and achieve the degree of deformation required to eliminate contact with the liquid. In some examples, the absorption condition may be a predetermined amount of voltage applied to the actuator through the third layer of material in response to immersion of the actuator in the pool of fluid (block 708).

[0097] 8 is a flow diagram illustrating a process 800 for forming a microfluidic device in one embodiment. Process 800 may include one or more operations, actions, or functions as illustrated by one or more of blocks 802, 804, or 806, or combinations thereof. Although illustrated as separate blocks, various blocks may be divided into further blocks, combined into fewer blocks, omitted, or performed in parallel, depending on the desired implementation.

[0098] Process 800 can begin at block 802, where a first layer can be bonded to a second layer to form an input layer. The first layer can include a first substrate layer and a first actuator layer of a paper-based analytical device (μPAD). The first actuator layer can extend a specific length from an edge of the first substrate layer of the μPAD. The first actuator layer can be made of a first material. The second layer can include a second substrate layer and a second actuator layer of the μPAD. The second actuator layer can extend a specific length from an edge of the second substrate layer of the μPAD. The second actuator layer can be made of a second material different from the first material. In some examples, the first material and the second material can have different swelling ratios. In some examples, the first material can be paper and the second material can be polypropylene. In some examples, the first substrate layer of the μPAD and the second substrate layer of the μPAD can be made of paper and wax.

[0099] In some examples, the second layer can be formed by a layer of conductive material. In some examples, the layer of conductive material can be located between the first actuator layer and the second actuator layer. In some examples, the layer of conductive material can be attached to the layer of active material (e.g., a layer of polypropylene) so that a voltage supplied to the layer of conductive material can stimulate the active material. In some examples, the layer of conductive material can be one of silver nanowires (AgNWs) and a combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS).

[0100] Process 800 may proceed from block 802 to block 804. At block 804, a reaction layer may be formed by bonding a third layer of μPADs including flow-directing elements to a fourth layer of μPADs including at least one reaction chamber. Process 800 may proceed from block 804 to block 806. At block 806, the input layer and reaction layer may be bonded to form a microfluidic device. The formed microfluidic device may include an actuator. The actuator may include a first actuator layer and a second actuator layer. The actuator may deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool.

[0101] The flowcharts and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present invention. In this regard, each block in the flowcharts or block diagrams may represent a module, segment, or portion of instructions, including one or more executable instructions for implementing the specified logical function(s). In some alternative implementations, the functions noted in the blocks may occur out of the order noted in the figures. For example, two blocks shown in succession may in fact be executed substantially in parallel, depending on the functionality involved, or the blocks may sometimes be executed in the reverse order. It will also be understood that each block in the block diagrams and / or flowchart diagrams, and combinations of blocks in the block diagrams and / or flowchart diagrams, can be implemented by a dedicated hardware-based system that performs the specified functions or operations, or a combination of dedicated hardware and computer instructions.

[0102] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the terms "comprises" and / or "comprising," when used herein, specify the presence of stated features, integers, steps, operations, elements, or components, or any combination thereof, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, or groups or combinations thereof.

[0103] The descriptions of various embodiments of the present invention have been presented for illustrative purposes, but are not intended to be exhaustive or to be limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terms used herein are chosen to best explain the principles of the embodiments, practical applications, or technical improvements to commercially available technology, or to enable those skilled in the art to understand the embodiments disclosed herein.

Claims

1. 1. An apparatus comprising: An analytical device; an actuator connected to the analytical device; and the actuator comprises: absorbing fluids; directing the absorbed fluid to an input layer of the analytical device; and Deformation in response to the occurrence of absorbing conditions wherein the degree of deformation of the actuator indicates the amount of fluid collected by the analysis device.

2. 10. The device of claim 1, wherein the actuator comprises a first layer of a first material and a second layer of a second material, the first material and the second material having different swelling rates.

3. 3. The device of claim 2, wherein the first material is paper and the second material is polypropylene.

4. The device of claim 1 , wherein the absorption condition comprises the actuator absorbing the fluid for a predetermined time.

5. The apparatus of claim 4 , wherein the amount of fluid collected by the analytical device is based on the predetermined time period.

6. The apparatus of claim 1 , wherein the analytical device is a microfluidic paper-based analytical device (μPAD).

7. 10. The device of claim 1, wherein the actuator comprises a first layer of a first material, a second layer of a second material, and a third layer of a third material, the first and second materials having different swelling ratios, and the third material is a conductive material.

8. the layer of conductive material Silver nanowires (AgNWs); The combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) 8. The device of claim 7, wherein the device is one of:

9. The apparatus of claim 7 , wherein the absorption condition is the application of a predetermined amount of voltage to the actuator through the layer of third material.

10. The apparatus of claim 9 , wherein the amount of fluid sampled by the analytical device is based on the predetermined voltage amount.

11. 1. A method for controlling the amount of fluid collected by an analytical device, comprising: immersing an actuator of a microfluidic device in a fluid pool to cause absorption of the fluid by the actuator, the actuator being connected to an analytical device of the microfluidic device; setting absorption conditions to control the amount of fluid collected by the analytical device; wherein the actuator deforms in response to the occurrence of the absorption condition, and the degree of deformation of the actuator indicates the amount of the fluid collected by the analytical device.

12. The method of claim 11 , wherein the actuator comprises a first layer of a first material and a second layer of a second material, the first material and the second material having different swelling ratios.

13. The method of claim 12, wherein the first material is paper and the second material is polypropylene.

14. The method of claim 11 , wherein setting the absorption condition includes setting a predetermined time for the actuator to absorb the amount of fluid.

15. The method of claim 11 , wherein the analytical device is a microfluidic paper-based analytical device (μPAD).

16. 12. The method of claim 11 , wherein the actuator comprises a first layer of a first material, a second layer of a second material, and a third layer of a third material, the first and second materials having different swelling ratios, and the third material is a conductive material.

17. the layer of conductive material Silver nanowires (AgNWs); The combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) 17. The method of claim 16, wherein the method is one of:

18. 17. The method of claim 16, wherein establishing the absorption condition comprises establishing a predetermined amount of voltage applied to the actuator through the layer of third material in response to immersion of the actuator in a pool of fluid.

19. 1. A method for forming a microfluidic device, comprising: a first layer including a first substrate and a first actuator layer, the first actuator layer extending a specific length from an edge of the first substrate, and the first actuator layer being made of a first material; and a second layer including a second substrate and a second actuator layer, the second actuator layer extending from an edge of the second substrate by the specified length, the second actuator layer being made of a second material different from the first material; forming a dosing layer by combining the a third layer containing flow elements; and a fourth layer including at least one reaction chamber; forming a reaction layer by bonding the combining the input layer and the reaction layer to form a microfluidic device; wherein the formed microfluidic device comprises an analytical device and an actuator, the actuator comprising the first actuator layer and the second actuator layer, the actuator configured to deform in response to the occurrence of an absorption condition involving immersion of the actuator in a liquid pool.

20. 20. The method of claim 19, wherein forming the injection layer comprises combining the first layer and the second layer with a layer of conductive material.

21. the layer of conductive material Silver nanowires (AgNWs); The combination of AgNWs and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) 21. The method of claim 20, wherein the

22. 20. The method of claim 19, wherein the first material and the second material have different swelling ratios.

23. 20. The method of claim 19, wherein the first material is paper and the second material is polypropylene.

24. 20. The method of claim 19, wherein the first substrate and the second substrate comprise paper and wax.

25. 20. The method of claim 19, wherein the analytical device is a microfluidic paper-based analytical device (μPAD).

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