DERMAL PATCH SYSTEM

Abstract

A system for collecting a physiological sample includes a dermal patch configured for attaching to a subject's skin and an applicator for coupling to the dermal patch. The dermal patch includes a reservoir configured to store a processing fluid, a sample collection chamber for receiving the processing fluid and a physiological sample extracted from a subject. The applicator includes at least one actuating lever for activating the dermal patch to receive the physiological sample from the subject and directing the physiological sample into the sample collection chamber.

Claims

1. A system for collecting a physiological sample, comprising: a dermal patch configured for attaching to a subject's skin, the dermal patch including: a reservoir configured to store a processing fluid, a sample collection chamber for receiving the processing fluid and a physiological sample extracted from a subject, an applicator having at least one actuating lever for activating the dermal patch to receive the physiological sample from the subject and directing the physiological sample into the sample collection chamber, wherein the applicator is configured to allow removable coupling of the actuating lever with the dermal patch.

2. The system of claim 1, further comprising at least one needle configured to be actuated via the actuating lever for puncturing the subject's skin.

3. The system of claim 1, wherein the actuating lever is configured to move from an undeployed position to a deployed position in which the actuator lever activates the dermal patch.

4. (canceled)

5. (canceled)

6. The system of claim 1, wherein the physiological sample comprises any of blood and interstitial fluid.

7. The system of claim 1, wherein the processing fluid includes a reagent or a buffer.

8. The system of claim 1, wherein the processing fluid includes an anti-coagulant.

9. The system of claim 1, wherein the processing fluid includes heparin or a protease inhibitor.

10. The system of claim 1, wherein the dermal patch further comprises a storage element in fluid communication with the sample collection chamber and configured to store the physiological sample received in the sample collection chamber.

11. The system of claim 10, wherein the storage element includes a filter paper matrix.

12. The system of claim 1, wherein the dermal patch includes an adhesive layer configured for attaching the dermal patch to the subject's skin.

13. The system of claim 1, wherein the applicator comprises a recess for receiving the dermal patch.

14. The system of claim 1, wherein the dermal patch includes one or more needles configured for actuation via the applicator for puncturing a subject's skin.

15. The system of claim 3, wherein the dermal patch comprises one or more fluidic channels for transferring any of the physiological sample and the processing fluid to the sample collection reservoir.

16. The system of claim 15, wherein the applicator is configured to create a vacuum in the one or more fluidic channels when the actuating lever is moved from the undeployed lever position to the deployed lever position.

17. The system of claim 16, wherein the applicator includes a pump configured for creating the vacuum.

18. The system of claim 17, wherein the pump includes a plunger and the actuating lever is configured to move the plunger from an inactive position to an active position when the actuating lever is moved from the undeployed lever position to the deployed lever position.

19. The system of claim 18, wherein the applicator further includes a release element configured to cause the processing fluid to flow out of the reservoir that is configured to store the processing fluid when the actuating lever is moved from the undeployed lever position to the deployed lever position.

20. The system of claim 19, wherein the dermal patch further includes a frangible membrane configured to seal the reservoir that is configured to store the processing fluid and the release element is configured to puncture the frangible membrane for releasing at least a portion of the processing fluid from the reservoir that is configured to store the processing fluid.

21. A system for collecting a physiological sample, comprising: a dermal patch configured for attaching to a subject's skin, the dermal patch including: a storage element for receiving and storing a physiological sample, an applicator having at least one actuating lever for activating at least one needle for puncturing the subject's skin to allow collecting the physiological sample from the subject and directing the physiological sample to said storage element, wherein the applicator is configured to allow removable coupling of the actuating lever with the dermal patch.

22. The system of claim 21, wherein said storage element includes a filter paper matrix.

23. The system of claim 21, further comprising a sample collection chamber in which said sample storage element is disposed.

24. The system of claim 23, further comprising a physiological fluid channel configured to carry the physiological sample extracted through the punctured skin to the sample collection chamber.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Aspects of the present disclosure may take form in various components and arrangements of components, and in various steps and arrangements of steps. The drawings are only for illustration purpose of preferred embodiments of the present disclosure and are not to be considered as limiting.

[0048] Features of embodiments of the present disclosure will be more readily understood from the following detailed description when taken in conjunction with the accompanying drawings in which:

[0049] FIG. 1 depicts a dermal patch and an applicator in accordance with an exemplary embodiment;

[0050] FIG. 2 is a cross sectional view of a dermal patch coupled to an applicator wherein an actuating lever of the applicator is in an undeployed position in accordance with an exemplary embodiment;

[0051] FIG. 3 depicts a dermal patch with two circular adhesive pads in accordance with an exemplary embodiment;

[0052] FIG. 4 depicts a dermal patch in accordance with an exemplary embodiment;

[0053] FIG. 5 depicts another dermal patch in accordance with an exemplary embodiment;

[0054] FIG. 6 is a cross sectional view of a dermal patch coupled to an applicator wherein an actuating lever of the applicator is in a deployed position in accordance with an exemplary embodiment;

[0055] FIG. 7 is a cross sectional view of a dermal patch coupled to an applicator wherein an actuating lever of the applicator is in an undeployed position in accordance with an exemplary embodiment;

[0056] FIG. 8 depicts another dermal patch in accordance with an exemplary embodiment;

[0057] FIG. 9 is a cross sectional view of a dermal patch coupled to an applicator wherein an actuating lever of the applicator is in a deployed position in accordance with an exemplary embodiment; and

[0058] FIG. 10 depicts a lancet and a dermal patch in accordance with an exemplary embodiment.

DETAILED DESCRIPTION

[0059] The present disclosure generally relates to a system and method that may be utilized to collect and store a physiological sample (e.g., blood, interstitial fluid, etc.) or detect a target analyte in a collected physiological sample.

[0060] In some embodiments, a dermal patch that is used to collect a physiological sample may include a processing fluid (e.g., reagent, buffer, anticoagulant, etc.). The processing fluid may be suitable for preserving the physiological sample. Providing a system with a dermal patch that includes a processing sample allows for the collection and preservation of a physiological sample within the dermal patch. Such a system may allow a user of the system to collect a physiological sample themselves at home and store the collected sample for further testing.

[0061] In other embodiments, a dermal patch that is used to detect a target analyte (e.g., a biomarker) in a physiological sample includes a needle to draw the physiological sample, a processing fluid, and a sensor that detects a target analyte. The processing fluid may be suitable for amplification of a target analyte (e.g., a primer). Providing a system with a dermal patch that includes a needle, a processing fluid, and a sensor allows for the drawing of a physiological sample and the detection of a target analyte within the dermal patch. Such a system may have enhanced sensitivity and/or specificity over other dermal patches that detect a target analyte.

[0062] Various terms are used herein in accordance with their ordinary meanings in the art, unless indicated otherwise. The term “about,” as used herein, denotes a deviation of at most 10% relative to a numerical value. The term “substantially,” as used herein, refers to a deviation, if any, of at most 10% from a complete state and/or condition. The terms “needle” and “microneedle” are used herein to broadly refer to an element that can provide a passageway, or facilitate the production of a passageway, for collecting a physiological sample, such as a blood or an interstitial fluid sample through a patient's skin, e.g., via puncturing the subject's skin. The term “transparent,” as used herein, indicates that light can substantially pass through an object (e.g., a window) to allow visualization of a material disposed behind the object. For example, in some embodiments, a transparent object allows the passage of at least 70%, or at least 80%, or at least 90%, of the visible light therethrough.

[0063] With reference to FIG. 1, a system 100 is disclosed in accordance with an exemplary embodiment. The system 100 includes a dermal patch 102 and an applicator 104. In some embodiments, the dermal patch 102 is removably coupled to the applicator 104. In other embodiments, the dermal patch 102 is integrally coupled to the applicator 104. While in this embodiment, the dermal patch 102 and the applicator 104 are formed of two portions that are coupled to one another, in other embodiments the dermal patch 102 and the applicator 104 may be formed as a single unit.

[0064] The dermal patch 102 and the applicator 104 may be formed from polymeric materials including, but not limited to, polymeric materials, e.g., polyolefins, PET (Polyethylene Terephthalate), polyurethanes, polynorbornenes, polyethers, polyacrylates, polyamides (Polyether block amide also referred to as Pebax®), polysiloxanes, polyether amides, polyether esters, trans-polyisoprenes, polymethyl methacrylates (PMMA), cross-linked trans-polyoctylenes, cross-linked polyethylenes, cross-linked polyisoprenes, cross-linked polycyclooctenes, inorganic-organic hybrid polymers, co-polymer blends with polyethylene and Kraton®, styrene-butadiene co-polymers, urethane-butadiene co-polymers, polycaprolactone or oligo caprolactone co-polymers, polylactic acid (PLLA) or polylactide (PL/DLA) co-polymers, PLLA-polyglycolic acid (PGA) co-polymers, and photocrosslinkable polymers. In some embodiments, at least a portion of the dermal patch 102 or the applicator 104 may be formed poly(dimethylsiloxane) (PDMS) to allow visibility of at least a portion of the components disposed with the dermal patch 102 or the applicator 104.

[0065] With reference to FIG. 2, the dermal patch 102 and the applicator 104 are further depicted in accordance with an exemplary embodiment wherein the dermal patch 102 is coupled to the applicator 104. As depicted in FIG. 2, the dermal patch includes an adhesive layer 106 for attaching the dermal patch 102 to a subject. Briefly turning to FIG. 3, another embodiment of the dermal patch 102 is further depicted. In this embodiment, the adhesive layer 106 includes a first circular patch 106A and a second circular patch 106B. The first circular patch 106A and the second circular patch 106B are connected to the dermal patch 102 via first connector 108A and a second connector 108B respectively. In this embodiment, when the dermal patch 102 is worn on an arm of a subject, the first connector 108A and the second connector 108B wrap around opposite sides the subject's arm thereby allowing the first circular patch 106A and the second circular patch 106B to adhere to opposite sides of the subject's arm.

[0066] Returning to FIGS. 2 and 4, the dermal patch 102 further includes a housing 110. The housing 110 includes a reservoir 112, a frangible membrane 114, a needle housing 116 including two needles 118, and a sample collection chamber 120 that receives the processing fluid and a physiological sample.

[0067] The reservoir 112 stores a processing fluid. In some embodiments, the processing fluid is suitable for preserving a physiological sample including, but not limited to, an anti-coagulant (e.g., heparin, a protease inhibitor, etc.). Furthermore, the frangible membrane 114 seals the processing fluid within the reservoir 112. In many embodiments, the reservoir 112 is pre-filled with the requisite processing fluid such that the dermal patch 102 can be used without a need to fill the reservoir 112 with the processing fluid at the point of care. In other words, a user can utilize the dermal patch 102 with all the requisite processing fluid on board. This feature provides distinct advantages in that it ensures consumer safety and reduces, and preferably eliminates, the risk of error. In other words, in many embodiments a dermal patch 102 contains all the necessary sample processing fluid for its intended use.

[0068] The needles 118 are configured to puncture a subject's skin and penetrate through a subject's stratum corneum and at least a portion of the epidermal layer to draw a physiological fluid (e.g., capillary blood and/or interstitial fluid). In some embodiments, the needles 118 may be movable between a retracted position and a deployed position. In the deployed position, the needles 118 are exposed for puncturing the skin. The needle housing 116 includes an opening that is in concert with an opening of the adhesive layer 106 which allows the needles 118 to contact the subject's skin when moved from a retracted to a deployed position. While FIG. 2 depicts the dermal patch 102 as include two needles 118, in other embodiments the dermal patch 102 may include a different number of needles 118 (e.g., 1, 4, 10, etc.).

[0069] With reference to FIG. 4, the reservoir 112 is in fluid communication with the sample collection chamber 120 via a processing fluid channel 124. The processing fluid channel 124 is configured to carry the processing fluid from the reservoir 112 to the sample collection chamber 120. The processing fluid channel 124 includes an inlet positioned beneath and in fluid communication with the reservoir 112. The inlet receives the processing fluid when the processing fluid is released from the reservoir 112. The processing fluid channel 124 further includes an outlet positioned beneath and in fluid communication with the sample collection chamber 120. Processing fluid exits the processing fluid channel 124 and enters the sample collection chamber 120 via the outlet.

[0070] The needle housing 116 is in fluid communication with the sample collection chamber 120 via a physiological fluid channel 126. The physiological fluid channel 126 is configured to carry the physiological sample from the needle housing 116 to the sample collection chamber 120. The physiological fluid channel 126 includes an inlet positioned beneath and in fluid communication with the needle housing 116. The inlet receives the physiological fluid when the needles 118 draw the physiological sample. The physiological fluid channel 126 further includes an outlet positioned beneath and in fluid communication with the sample collection chamber 120. The physiological fluid exits the physiological fluid channel 126 and enters the sample collection chamber 120 via the outlet.

[0071] When the processing fluid and the physiological sample enter the collection chamber 120, the processing fluid mixes and interacts with the physiological sample to form a processed physiological sample. In this embodiment, the processed physiological sample is suitable for storage. The processed physiological sample is stored within the sample collection chamber 120 and may be further analyzed at a later time.

[0072] FIG. 5 depicts an embodiment of the dermal patch 102, wherein the dermal patch 102 includes a storage element 128. The storage element 128 is in fluid communication with the sample collection chamber 120 and configured to store a processed physiological sample received in the sample collection chamber 120. The storage element 128 may include, but is not limited to, a filter paper matrix.

[0073] Returning to FIG. 2, the applicator 104 includes an actuating lever 130. As will be discussed in further detail herein, the actuating lever 130 is moveable between an undeployed position (FIG. 2) and a deployed position (FIG. 6) within a chamber 131 of the housing 110. The applicator 104 further includes a needle activation element housing 132 that includes a needle activation element 134, a pump housing 136 that includes a pump 138, and a release element housing 140 that includes a release element 142.

[0074] The needle activation element 134 is moveable between an undeployed position (FIG. 2) to a deployed position (FIG. 6) within the needle activation element housing 132. The actuating lever 130 moves the needle activation element 134 when the actuating lever 130 is moved from the undeployed position to the deployed position. The needle activation element housing 132 includes an opening 144 that is in concert with an opening 146 of the needle housing 116. When moved, the needle activation element 134 moves through the openings 144 and 146 and causes the needles 118 to move from the retracted position to the deployed position which causes the needles 118 to puncture the subject's skin to draw the physiological sample.

[0075] The pump housing 136 includes an opening 148 that is in fluid communication with a vacuum channel 150. As depicted in FIG. 4, the vacuum channel 150 is in fluid communication with the sample collection chamber 120. As a result, the vacuum channel 150 is also in fluid communication with the needle housing 116. The pump 138 includes a plunger 152 that is moveable between an inactive position (FIG. 2) and an active position (FIG. 6) within the pump hosing 136. The actuating lever 130 moves the plunger 152 when the actuating lever 130 is moved from the undeployed position to the deployed position. The pump 138 is configured to create a vacuum within the dermal patch 102. More specifically, the pump 138 is configured to create vacuum within the vacuum channel 150 by evacuating the vacuum channel 150 to a pressure below the atmospheric pressure when the plunger 152 is moved to the active position. This vacuum draws the physiological sample through the physiological fluid channel 126 and into the sample collection chamber 120.

[0076] The release element 142 is moveable between an undeployed position (FIG. 2) to a deployed position (FIG. 6) within the release element housing 140. The actuating lever 130 moves the release element 142 when the actuating lever 130 is moved from the undeployed position to the deployed position. The release element housing 140 includes an opening 154 that is in concert with an opening 156 of the dermal patch 102 that is vertically above the reservoir 112. When moved, the release element 142 moves through the openings 154 and 156 and causes the release element to release the processing fluid thereby and causes the processing fluid to flow out of the reservoir 112. When released, the processing fluid enters the processing fluid channel 126 and flows to the sample collection chamber 120. In embodiments wherein the dermal patch 102 includes the frangible membrane 114, the release element 142 breaks the frangible membrane to release the processing fluid. In some embodiments, the release element 142 punctures the frangible membrane to release the processing fluid.

[0077] With reference to FIGS. 7 and 8, a system 200 is disclosed in accordance with an exemplary embodiment. The system 200 includes a dermal patch 202 and the applicator 104. In some embodiments, the dermal patch 202 is removably coupled to the applicator 104. In other embodiments, the dermal patch 202 is integrally coupled to the applicator 104. The dermal patch 202 and the applicator 104 may be formed from polymeric materials as previously discussed herein.

[0078] The dermal patch 202 includes an adhesive layer 206 for attaching the dermal patch 202 to a subject. In some embodiments the adhesive layer 206 includes two circular patches as depicted in FIG. 3. The dermal also includes a housing 210. The housing 210 includes a reservoir 212, a frangible membrane 214, a needle housing 216 including two needles 218, and a sensor 220 that receives the processing fluid and a physiological sample.

[0079] The reservoir 212 stores a processing fluid. In some embodiments, the processing fluid is suitable for isothermal amplification a target analyte, including but not limited to, a primer. In many embodiments, the reservoir 212 is pre-filled with the requisite processing fluid such that the dermal patch 202 can be used without a need to fill the reservoir 212 with the processing fluid at the point of care as previously discussed herein.

[0080] The needles 218 are configured to puncture a subject's skin and penetrate through a subject's skin to draw a physiological sample and may be movable between a retracted position and a deployed position as previously discussed herein. The needle housing 216 includes an opening 222 that is in concert with an opening of the adhesive layer 106 which allows the needles 218 to contact the subject's skin when moved from a retracted to a deployed position. While FIG. 7 depicts the dermal patch 202 as include two needles 218, in other embodiments the dermal patch 202 may include a different number of needles 218 (e.g., 1, 4, 10, etc.).

[0081] With reference to FIG. 8, the reservoir 212 is in fluid communication with the sensor 220 via a processing fluid channel 224. The processing fluid channel 224 is configured to carry the processing fluid from the reservoir 212 to the sensor 220. The processing fluid channel 224 includes an inlet positioned beneath and in fluid communication with the reservoir 212. The inlet receives the processing fluid when the processing fluid is released from the reservoir 212. The processing fluid channel 224 further includes an outlet positioned beneath and in fluid communication with the sensor 220. Processing fluid exits the processing fluid channel 224 and enters the sensor 220 via the outlet.

[0082] The needle housing 216 is in fluid communication with the sensor 220 via a physiological fluid channel 226. The physiological fluid channel 226 is configured to carry the physiological sample from the needle housing 216 to the sensor 220. The physiological fluid channel 226 includes an inlet positioned beneath and in fluid communication with the needle housing 216. The inlet receives the physiological fluid when the needles 218 draw the physiological sample. The physiological fluid channel 226 further includes an outlet positioned beneath and in fluid communication with the sensor 220. The physiological fluid exits the physiological fluid channel 226 and enters the sensor 220 via the outlet.

[0083] When the processing fluid and the physiological sample enter the collection chamber 220, the processing fluid mixes and interacts with the physiological sample to form a processed physiological sample. The sensor 220 may then detect a target analyte within the processed physiological sample. In some embodiments, the sensor 220 may detect a target analyte when the target analyte is equal to or greater than a threshold (e.g., a limit-of detection (LOD)). In other embodiments, the sensor may be calibrated to determine a quantitative level of the target analyte (e.g., the concentration of the target analyte in the collected sample).

[0084] The sensor 220 may be a variety of different sensors capable of detecting a target analyte (e.g., a graphene-based detector, a chemical detector, a lateral flow sensor, a DNA sequencing sensor, an RNA sequencing sensor, etc.). Furthermore, the sensor 220 may be a passive sensor or an active sensor and may provide chromatographic or “photo-visual,” or digital readouts (e.g., a colorimetric sensor, an immunoassay sensor including lateral flow sensors, isothermal amplification detection systems, etc.). In some embodiments in which a colorimetric sensor is employed, at least a portion of the dermal patch may include a transparent portion to allow the visualization of the sensor 220.

[0085] As previously discussed herein, the sensor 220 is in fluid communication with the processing fluid channel 224 and the physiological fluid channel 226 for coming into contact with at least a portion of the processed physiological sample and to generate one or more signals in response to the detection of a target analyte, when present in the sample. By way of example, the sensor 220 can be coupled to processing fluid channel 224 and the physiological fluid channel 226 via a sealed opening. Other suitable means for interrogating a sample may also be employed. By way of example, in some cases, the interrogation of a processed physiological sample may be achieved without the need for direct contact between a sensor 220 and the sample (e.g., optical techniques, such as fluorescent and/or Raman techniques).

[0086] In some embodiments, the dermal patch 202 may include circuitry 221 that is in communication with the sensor 220 of the dermal patch 202 and receives one or more signals (e.g., detection signals) generated by the sensor 220. The circuitry 221 may be configured to process the signals to determine the presence of a target analyte in the processed physiological sample and optionally quantify the level of the target analyte, when present in the processed physiological sample. In addition or instead, the signals generated by the sensor 220 may be processed the circuitry 221 or an external device to quantify the level of the target analyte detected in the sample. By way of example, such quantification may be implemented using previously-generated calibration data in a manner known in the art as informed by the present teachings. In these embodiments, the circuitry

[0087] The circuitry 221 may be implemented using the techniques known in the art. By way of example, the circuitry may include at least one memory module for storing the signals generated by the sensor 220. The circuitry 221 may be configured to process the stored signals, e.g., detection signals, generated by different types of sensor 220. The circuitry 221 may also include a communication module to allow communication between the circuitry 221 and an external electronic device. Such an external electronic device may be a mobile electronic device. By way of example, in some embodiments, a variety of wireless communication protocols may be used for transmitting data from the circuitry to the external electronic device. Some examples of such wireless communication protocols may include Bluetooth, Wi-Fi, and BTLE protocol for establishing a communication link between the patch and the electronic device.

[0088] The circuitry 221 may be implemented on a printed circuit board (PCB), that is in communication with the sensor 220. The connection between the circuitry 221 and the sensor 220 may be established via any of a wired or wireless protocol. In some embodiments, the circuitry 221 and/or the sensor 220 can be supplied with power via an on-board power supply, e.g., a battery, incorporated, e.g., on the circuitry. Alternatively, in some implementations, the circuitry and/or the sensor can be provided with power via an external device, e.g., a wearable device. Such transfer of power from an external device may be achieved using techniques known in the art, such as inductive coupling between two elements (e.g., two coils) provided in the dermal patch and the external device.

[0089] The circuitry 221 may include an application-specific integrated circuit (ASIC) that is configured for processing the signal data generated by the sensor 220. The circuitry 221 can further include one or more memory modules for storing, for example, instructions for processing the data generated by the sensor 220.

[0090] While FIG. 8 depicts the dermal patch 202 as including the circuitry 221, in some embodiments the circuitry 221 may be omitted. In these embodiments, the sensor 220 may detect the target analyte without any circuitry 221 needed (e.g., a lateral flow assay).

[0091] In some embodiments, a target analyte may be a pathogen, e.g., a virus or a bacterium. In some embodiments, the sensor 220 can be configured to detect such a pathogen via the detection of a protein or a genetic material thereof, e.g., segments of its DNA and/or RNA. In other embodiments, the sensor 220 may be a lateral flow sensor that can be employed to detect a hormone. In other embodiments, the target analyte may be a biomarker, e.g., a biomarker that may be indicative of a disease condition, e.g., organ damage. In some embodiments, the biomarker may be indicative of a traumatic brain injury (TBI), including a mild traumatic brain injury. Some example of such a biomarker include, without limitation, any of myelin basic protein (MBP), ubiquitin carboxyl-terminal hydrolase isoenzyme L1 (UCHL-1), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), and S100-B.

[0092] In other embodiments, the dermal patch may be configured for the detection of other biomarkers, such as troponin, brain natriuretic peptide (BnP), and HbA 1C. Other examples include, but are not limited to, Cardiac troponin I protein (cTnl), Cardiac troponin T protein (cTnT), C-reactive protein (CRP), B-type natriuretic peptide (BNP), Myeloperoxidase, Creatine kinase MB, Myoglobin, Hemoglobin, HbA1C.

[0093] Further, in some embodiments, the sensor 220 may be configured to detect one or more biomarkers for diagnosis of brain damage, such as traumatic brain injury (TBI). Some examples of such biomarkers include, but are not limited to, myelin basic protein (MBP), ubiquitin carboxyl-terminal hydrolase isoenzyme L1 (UCHL-1), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), and S100-B.

[0094] By way of example, the sensor 220 may be configured to measure levels of the protein biomarkers UCHL-1 and GFAP, which are released from the brain into blood within 12 hours of head injury. The levels of these two proteins measured by the sensor 220 according to the present disclosure after a mild TBI can help identify those patients that may have intracranial lesions.

[0095] In one embodiment a target analyte may be detected the sensor 220 when the sensor 220 is a graphene-based sensor that includes a graphene layer that is functionalized with a moiety (e.g., an antibody, an aptamer, an oligonucleotide, etc.) that exhibits specific binding to that target analyte (e.g., a protein, a DNA segment) such that upon binding of the target analyte to that moiety an electrical property of the underlying graphene layer changes, thus indicating the presence of the target analyte in the sample. Some examples of suitable graphene-based sensors are disclosed in U.S. Pat. Nos. 10,782,285, 10,401,352, 9,664,674, as well as published U.S. Patent Applications Nos. 20200011860, and 20210102937, each of which is herein incorporated by reference in their entirety.

[0096] By way of example, the detection of a target analyte may be achieved by using a graphene-based sensor and/or an electrochemical sensor that is functionalized with a probe, such as an antibody and/or aptamer, which exhibits specific binding to that target analyte, though other sensing technologies may also be utilized.

[0097] In another embodiment, the sensor 220 may be an electrochemical sensor that can function in a faradaic or non-faradaic mode to detect a target analyte of interest. For example, such an electrochemical sensor may include a working electrode, a reference electrode and a counter electrodes. By way of example, in some embodiments, the reference electrode may be functionalized with a moiety that exhibits specific binding to a target analyte such that upon binding of that target analyte, when present in the sample, to the moiety, a change in the current through the circuit may be detected.

[0098] In some embodiments, at least one serum-separation element is associated with the sensor 220 for receiving blood and separating a serum/plasma component of the blood for introduction into said at least one of the sensing units.

[0099] The serum-separating element may include a fibrous element that is configured to capture one or more cellular components of the blood so as to separate a plasma/serum component of the blood for analysis. For example, in such embodiments, the serum component can be introduced in a respective sensing unit for analysis, e.g., for detection and optionally quantification of one or more biomarkers and/or other analytes. In some embodiments, the serum-separating element is a nitrocellulose strip. The use of such a fibrous element, and in particular a nitrocellulose strip, can allow sufficient fractionation of the blood to enhance significantly the sensitivity/specificity of detection of analytes (e.g., biomarkers) in the separated serum, especially using a graphene-based sensor. In other words, although the use of a nitrocellulose strip in a patch according to some embodiments may not result in fractionation of the whole blood sample with the same degree of separation quality that is achievable via traditional fractionation methods, such as differential centrifugation; nonetheless, the applicant has discovered that the use of such a nitrocellulose strip in embodiments of the dermal patch can significantly enhance the sensitivity/specificity for the detection of a variety of analytes (e.g., biomarkers) using a variety of detectors, such as graphene-based detectors, relative to the use of a whole blood sample for such detection. In some embodiments, wherein the sensor 220 is a graphene sensor, the nitrocellulose strip may be coupled to the sensor 220 and the sensor 220 may detect the target analyte via the nitrocellulose strip.

[0100] Furthermore, the serum-separation element may include at least one fibrous membrane configured to capture at least a portion of one or more cellular components of the received blood, thereby separating a serum (or a plasma) component of the blood.

[0101] In some embodiments, the separated plasma or the serum component can still include some cellular elements. Even without having a level of fractionation that is achieved via traditional methods, such as differential centrifugation, the separated serum component can be utilized to achieve an enhanced detection sensitivity/specificity relative to using whole blood for detecting, and optionally quantifying, a variety of target analytes in a drawn blood sample. Some examples of such target analytes may include, without limitation, a biomarker, such as troponin, brain natriuretic peptide (BnP), or other biomarkers including those disclosed herein.

[0102] The separated serum component may include any of a plurality of red blood cells and/or a plurality of white blood cells and/or platelets. However, the concentration of such cellular components in the separated serum component can be less than that in the whole blood by a factor in a range of about 2 to about 1000, though lower concentrations can also be achieved.

[0103] Returning to FIG. 7, the applicator 104 includes an actuating lever 130. As previously discussed herein, the actuating lever 130 is moveable between an undeployed position (FIG. 7) and a deployed position (FIG. 9) within a chamber 131 of the housing 110.

[0104] The needle activation element 134 is moveable between an undeployed position (FIG. 7) to a deployed position (FIG. 9) within the needle activation element housing 132 as previously discussed herein. The actuating lever 130 moves the needle activation element 134 when the actuating lever 130 is moved from the undeployed position to the deployed position. When moved, the needle activation element 134 moves through the openings 144 and 246 and causes the needles 218 to move from the retracted position to the deployed position which causes the needles 218 to puncture the subject's skin to draw the physiological sample.

[0105] In this embodiment, the opening 148 of the pump housing 136 is in fluid communication with a vacuum channel 250 of the dermal patch 200. As depicted in FIG. 7, the vacuum channel 250 is in fluid communication with the sensor 220. As a result, the vacuum channel 250 is also in fluid communication with the needle housing 216.

[0106] The actuating lever 130 moves the plunger 152 when the actuating lever 130 is moved from the undeployed position to the deployed position and the pump 238 is configured to create a vacuum within the dermal patch 202 as previously discussed herein. More specifically, the pump 238 is configured to create vacuum within the vacuum channel 250 when the plunger 152 is moved to the active position. This vacuum draws the physiological sample through the physiological fluid channel 226 and to the sensor 220.

[0107] The release element 142 is moveable between an undeployed position (FIG. 7) to a deployed position (FIG. 9) as previously discussed herein. In this embodiment the opening 154 that is in concert with an opening 256 of the dermal patch 202 that is vertically above the reservoir 212. When moved, the release element 142 moves through the openings 154 and 256 and causes the release element to release the processing fluid thereby and causes the processing fluid to flow out of the reservoir 212 as. When released, the processing fluid enters the processing fluid channel 226 and flows to the sensor 220. In embodiments wherein the dermal patch 202 includes the frangible membrane 214, the release element 142 breaks the frangible membrane to release the processing fluid. In some embodiments, the release element 142 punctures the frangible membrane to release the processing fluid.

[0108] In some embodiments, rather than utilizing an applicator, a dermal patch according to the present teachings can be activated by a user using an implement, e.g., a lancet enclosed in a trocar. By way of example, with reference to FIG. 10, a dermal patch 102 according to the present teachings can be coupled to a patient's upper arm, e.g., via an elastic band having a hook-and-loop fastener that can apply a moderate pressure to the subject's arm. A lancet 902 can be used to penetrate through a septum 904 of the dermal patch 104 so as to puncture the skin so as to allow blood to enter the dermal patch under the influence of the pressure applied to the subject's arm. The lancet 902 may include a pressure or a vacuum bulb that a user may push to promote the flow of the physiological sample to the sample collection chamber 902.

[0109] Subsequently, the same trocar having a lancet can be used to cause the release of the processing fluid (or at least a portion thereof) from the fluid reservoir for mixing with the drawn blood sample. For example, the lancet may retracted into the trocar and the tip of the trocar can be pressure on a flexible membrane sealing the fluid reservoir to cause the fluid to be released from the fluid reservoir, e.g., in a manner discussed above in connection with the applicator.

[0110] In other embodiments, the needles 118, after drawing the physiological sample, may apply positive pressure to push the drawn physiological sample to the sample collection chamber 120. In these embodiments, the pump 138 and the vacuum channel 150 may be omitted.

[0111] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; embodiments of the present disclosure are not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing embodiments of the present disclosure, from a study of the drawings, the disclosure, and the appended claims.

[0112] In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single processor or other processing unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measured cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.