# US 12,433,510 B2 · Methods and systems for improved collection of interstitial fluid > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,433,510 B2 - Document ID: US12433510B2 - Status: Granted - Kind: B2 - Application number: 16/955,681 - Filed: 2018-12-21 - Published: 2020-10-08 - Granted: 2025-10-07 - Earliest claimed: 2017-12-21 - Assignees: Georgia Tech Research Corporation - Applicants: Georgia Tech Research Corporation - Inventors: Pradnya Samant; Chandana Kolluru; Mark R. Prausnitz - Web page: https://patentgrep.com/patent/US12433510B2 ## CPC - A61B 5/14514: {using means for aiding extraction of interstitial fluid, e.g. microneedles or suction} - A61B 5/150022: {for capillary blood or interstitial fluid} - A61B 5/150068: {by tissue compression, e.g. with specially designed surface of device contacting the skin area to be pierced} - A61B 5/150099: {by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes} - A61B 5/150748: {Having means for aiding positioning of the piercing device at a location where the body is to be pierced (means for aiding positioning of devices for bringing media into the body A61M5/427, locating blood vessels A61B5/489)} - A61B 5/150984: {Microneedles or microblades} - A61B 10/0045: {Devices for taking samples of body liquids} - A61B 17/205: {Vaccinating by means of needles or other puncturing devices} - A61B 5/145: Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value {; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue} (non-radiation detecting or locating of foreign bodies in blood A61B5/06) - A61B 5/14507: {specially adapted for measuring characteristics of body fluids other than blood (devices for taking samples of body liquids A61B10/0045)} - A61B 5/1451: {for interstitial fluid} - A61B 5/15: Devices for taking samples of blood - A61B 5/150015: {Source of blood} - A61B 18/00: Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body (eye surgery A61F9/007; ear surgery A61F11/00) - A61B 2010/008: {Interstitial fluid} - A61B 2018/143: {multiple needles} - A61M 37/0015: {by using microneedles} - A61M 2037/0023: {Drug applicators using microneedles} - A61M 2037/003: {having a lumen} - A61M 2037/0038: {having a channel at the side surface} - A61M 2037/0046: {Solid microneedles} - A61M 2037/0061: {Methods for using microneedles} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} ## Abstract Methods and devices of collecting ISF from skin. The methods may include inserting an array of microneedles into a patient's skin to form apertures in the patient's skin, facilitating ISF mobilization within the skin, and collecting ISF that flows from the apertures. The devices may include an array of microneedles extending from a backing structure. The devices also may include a collection matrix for collecting ISF and/or means for facilitating ISF mobilization. ## Claims ### Claim 1 A method for collecting interstitial fluid (ISF) from a patient's skin, the method comprising: inserting a plurality of microneedles into the patient's skin at an insertion site to form a plurality of apertures in the patient's stratum corneum at the insertion site; inducing local edema to mobilize ISF within the patient's dermis at the insertion site; and collecting the ISF that flows from the apertures to a surface of the patient's skin at the insertion site, wherein the inducing the local edema within the patient's dermis is effective to increase a rate and/or a total amount of the ISF flowing from the apertures. ### Claim 2 (depends on 1) The method of claim 1, wherein the inducing the local edema is effected by selective application of pressure and/or heat to the patient's skin at or about the insertion site. ### Claim 3 (depends on 2) The method of claim 2, wherein the selective application of pressure comprises applying the pressure at a specific location with specific intensities using a pressure cuff or elastic band to restrict the venous flow and/or the lymphatic flow, but restrict the arterial flow to a lesser extent. ### Claim 4 (depends on 2) The method of claim 2, wherein the selective application of pressure comprises applying the pressure with a device element to which the plurality of microneedles is connected. ### Claim 5 (depends on 1) The method of claim 1, wherein the inducing the local edema is effected by inserting the microneedles at the insertion site in a manner effective to generate an injury response. ### Claim 6 (depends on 1) The method of claim 1, wherein the microneedles are inserted into the skin at an angle from about 10° to about 45° relative to the skin surface. ### Claim 7 (depends on 1) The method of claim 1, wherein the ISF flows from the apertures, along an outer surface of the microneedles, while the microneedles remain inserted in the patient's skin. ### Claim 8 (depends on 7) The method of claim 7, wherein the microneedles are repeatedly pressed in and out of the patient's skin. ### Claim 9 (depends on 1) The method of claim 1, wherein the inducing the local edema is carried out at a first time, and the collection of the ISF occurs at or after a second time at least one minute after the first time. ### Claim 10 (depends on 1) The method of claim 1, wherein the plurality of microneedles is inserted into and removed from the insertion site several times before or during the collecting the ISF. ### Claim 11 (depends on 1) The method of claim 1, wherein the patient's skin at the insertion site is manipulated to be held in a taut and/or curved position during (i) the inserting the plurality of microneedles, and/or (ii) the collecting the ISF. ### Claim 12 (depends on 1) The method of claim 1, which is performed in a manner that the collected ISF is substantially or completely blood-free. ### Claim 13 (depends on 1) A method for detection and/or monitoring of disease, injury, environmental exposure, or physiological or drug pharmacokinetic status, the method comprising: collecting the interstitial fluid (ISF) from the patient's skin in accordance with the method of claim 1; and analyzing the collected ISF for a presence or concentration of (i) a biomarker indicative of the disease, the injury, the environmental exposure, or the physiological status, (ii) a pharmaceutical compound, (iii) a metabolite, or (iv) a combination thereof. ### Claim 14 (depends on 1) The method of claim 1, wherein the inducing the local edema is effected by a laser treatment of the patient's skin. ### Claim 15 (depends on 14) The method of claim 14, wherein the laser treatment comprises an ablative or non-ablative fractional laser treatment. ### Claim 16 (depends on 1) The method of claim 1, wherein the inducing the local edema is effected by treating the patient's skin with radiofrequency energy. ### Claim 17 (depends on 16) The method of claim 16, wherein the radiofrequency energy is applied with an electrode, and the electrode comprises at least one microneedle of the plurality of microneedles. ### Claim 18 (depends on 1) The method of claim 1, wherein the inducing the local edema is effected by treating the patient's skin with ultraviolet light, visible light, near infrared light, infrared light, or a combination thereof. ### Claim 19 (depends on 18) The method of claim 18, wherein the ultraviolet light, the visible light, the near infrared light, the infrared light, or the combination thereof induces production of a heat shock protein in the patient's skin. ### Claim 20 A device for collection of interstitial fluid (ISF) from a patient's skin, the device comprising: an array of solid microneedles configured for insertion across the stratum corneum of the patient's skin, each solid microneedle having an outer surface, an insertion tip end portion, and a base end portion; a backing structure from which the array of microneedles extends; an ISF collection matrix disposed in proximity to the base end portion of the microneedles to receive the ISF flowing along the outer surface toward the base end portion of the microneedles when the microneedles are inserted into the patient's skin; and a means for inducing local edema to mobilize ISF within the patient's dermis at an insertion site where the microneedles are inserted into the patient's skin. ### Claim 21 A device for collection of interstitial fluid (ISF) from a patient's skin, the device comprising: an array of solid microneedles configured for insertion across the stratum corneum of the patient's skin, each solid microneedle having an outer surface, an insertion tip end portion, and a base end portion; a backing structure from which the array of microneedles extend; and a means for inducing local edema to mobilize ISF within the patient's dermis at an insertion site where the microneedles are inserted into the patient's skin. ### Claim 22 A method for collecting interstitial fluid (ISF) from a human subject's skin, the method comprising: inserting a plurality of microneedles into the human subject's skin at an insertion site to form a plurality of apertures in the subject's stratum corneum at the insertion site; inducing local edema, without use of a bioactive agent, to mobilize ISF within the subject's dermis at the insertion site; and collecting the ISF that flows from the apertures to a surface of the human subject's skin, wherein the inducing the local edema within the subject's dermis is effective to increase a rate and/or a total amount of the ISF flowing from the apertures.