Systems and methods for monitoring health and delivering drugs transdermally

• US 20050182307A1
• Filed: 03/28/2005
• Published: 08/18/2005
• Est. Priority Date: 06/01/2000
• Status: Active Grant

• Current Assignee: Georgetown University, Leidos, Inc. (Leidos Holdings, Inc.)
• Original Assignee: Dermal Systems International, Inc., Georgetown University, Science Applications International Corporation
• Inventors: Peck, Carl C., White, Robert C., Schneider, Thomas W., Paranjape, Makarand, Currie, John F.
• Granted Patent: US 7,931,592 B2
• Time in Patent Office: Days
• US Class Current: 600/300
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/150007 Details
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

The present invention pertains to a system and method for transdermal sampling, comprising: at least one sampler for retrieving and transferring at least one analyte obtained transdermally from the skin of a subject; at least one detector system for identifying and quantifying said at least one analyte; and at least one logic module for (i) receiving and storing input data from said at least one detector, (ii) relating the input data to other data obtained from the subject, (iii) displaying output information, (iv) transmitting the output information to another system, and (v) controlling the operation of said at least one sampler and at least one detector.

Claims

1-114. -114. (canceled)

115. A transdermal sampling system, comprising:

at least one sampler for retrieving and transferring at least one analyte obtained transdermally from the skin of a subject, wherein the sampler is a microfabricated device comprising a microfluidic assembly;

at least one detector system for identifying and quantifying said at least one analyte; and

at least one logic module for (i) receiving and storing input data from said at least one detector, (ii) relating the input data to other data obtained from the subject relating to the condition of the subject, (iii) displaying output information indicative of health and clinical state of the subject as determined from the relating of the input data to the other data, (iv) transmitting the output information to another system, and (v) controlling the operation of said at least one sampler and at least one detector.

117. The system of claim 115, wherein said at least one sampler further comprises means for enhancing permeability of the skin of a subject for retrieving said at least one analyte therefrom.

118. The system of claim 117, wherein said means for enhancing permeability comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface, and configured for ablating a portion of the stratum corneum of the skin of a subject and collects of interstitial fluid from the subject'"'"'s underlying viable epidermis.

119. The system of claim 117, wherein said means for enhancing permeability comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface, and configured for ablating a portion of the stratum corneum of the skin of a subject and accesses interstitial fluid from the subject'"'"'s underlying viable epidermis.

120. The system of claim 117, wherein said means for enhancing permeability of the skin comprises a radiation source positioned for generating and directing radiation to a subject'"'"'s skin surface, effective to ablate a portion of the stratum corneum of the skin of a subject, to allow collection of interstitial fluid from the subject'"'"'s underlying viable epidermis.

121. The system of claim 120, wherein said radiation source is a light source.

122. The system of claim 121, wherein said light source is a laser.

123. The system of claim 117, wherein said means for enhancing permeability of the skin comprises a radiation source positioned for generating and directing radiation to a subject'"'"'s skin surface, effective to ablate a portion of the stratum corneum of the skin of a subject, to allow diffusion from interstitial fluid from the subject'"'"'s underlying viable epidermis.

124. The system of claim 117, wherein said means for enhancing permeability of the skin is at least one of:

(i) means for chemically altering the surface of the skin;

(ii) means for puncturing the surface of the skin;

(iii) means for solubilizing the surface of the skin;

(iv) means for illuminating the surface of the skin sufficient to cause ablation thereof; and

(v) means for irradiating the surface of the skin to cause ablation thereof.

125. The system of claim 115, wherein said at least one detector system comprises an optical detection system comprised of at least one light source effective to excite fluorophores, and at least one detector for detecting fluorescence from excited fluorophores.

126. The system of claim 125, wherein said light source comprises at least one LED or at least one laser.

130. The system of claim 115, further comprising an adhesive to substantially adhere the sampler to the skin of the subject.

134. The system of claim 115, further comprising means for monitoring predetermined physiological data as said other data, for relating to the input data by said at least one logic module.

135. The system of claim 115, further comprising means for monitoring environmental conditions data as said other data, for relating to the input data by said at least one logic module.

136. The system of claim 115, wherein said at least one detector system comprises a patch sensitive to at least one analyte for changing color in response to contact with said at least one analyte, and at least one detector for detecting a change in color of the patch.

146. The device of claim 115, wherein said at least one detector system comprises an optical detection system comprised of a light source effective to excite fluorophores, and at least one detector for detecting fluorescence from excited fluorophores.

147. The device of claim 146, wherein said light source is selected from the group consisting of at least one LED or at least one laser.

179. The transdermal sampling system according to claim 115, wherein the microfluidic assembly comprises at least one serpentine capillary channel.

180. The transdermal sampling system according to claim 115, wherein the microfluidic assembly further comprises:

at least one reservoir channel;

at least one bottom capping section; and

at least one top capping section.

181. The transdermal sampling system according to claim 180, wherein the at least one reservoir channel further comprises at least one seal for retaining a physiologically compatible fluid within the at least one reservoir channel.

182. The transdermal sampling system according to claim 181, wherein the at least bottom capping section comprises a micro-heating element.

183. The transdermal sampling system according to claim 182, wherein the micro-heating element serves to ablate stratum corneum.

184. The transdermal sampling system according to claim 182, wherein the micro-heating element serves to rupture the at least one seal.

185. The transdermal sampling system according to claim 182, wherein the micro-heating element serves both to ablate stratum corneum and to rupture the at least one seal.

186. The transdermal sampling system according to claim 180, wherein the at least one top capping section comprises two or more electrodes.

187. The transdermal sampling system according to claim 186, wherein the two or more electrodes serve to assist the flow of a physiologically compatible fluid through an at least one serpentine capillary channel.

188. The transdermal sampling system according to claim 180, further comprising a sensor for detecting the at least one analyte.

189. The transdermal sampling system according to claim 188, wherein the sensor for detecting the at least one analyte comprises a patch sensitive to the at least one analyte for changing color in response to contact with the at least one analyte, and at least one detector for detecting a change in color of the patch.

190. The transdermal sampling system according to claim 115, wherein the microfluidic assembly contains a physiologically compatible fluid that transfers at least one analyte obtained transdermally from the skin of a subject.

191. The transdermal sampling system according to claim 130, wherein the adhesive substantially prevents movement of the transdermal sampling system relative to the skin of the subject.

192. The transdermal sampling system according to claim 130, wherein the adhesive serves to prevent loss of the physiologically compatible fluid.

193. The transdermal sampling system according to claim 130, wherein the adhesive is water impermeable.

194. The transdermal sampling system according to claim 115, wherein at least one surface of the microfluidic assembly is modified in a manner to enhance sampling function.

195. The transdermal sampling system according to claim 194, wherein the modification of the at least one surface of the microfluidic assembly prevents the adsorption of protein to the at least one surface of the microfluidic assembly.

196. The transdermal sampling system according to claim 194, wherein the modification of the at least one surface of the microfluidic assembly attaches to the at least one surface of the microfluidic assembly at least one specific-binding molecule which specifically binds the at least one analyte.

208. The transdermal sampling system according to claim 181, wherein the seal is semi-permeable or selectively permeable.

137. A microfabricated device for allowing remote monitoring of a subject, comprising:

at least one sampler unit body for retrieving and transferring at least one analyte obtained transdermally from the skin of a subject, wherein the sampler unit body is a microfabricated device comprising a microfluidic assembly;

at least one detector system connected to said at least one sampler unit body for identifying and quantifying at least one analyte obtained from a subject; and

a transmitter/receiver for transmitting data relating to at least one analyte detected by said detection system to a logic module for processing thereby, and for allowing control of the microfabricated device by a logic module.

138. The device of claim 137, wherein said microfluidic assembly comprises:

at least one reservoir;

at least one conduit in communication with the at least one reservoir, wherein the at least one conduit receives the at least one analyte from the at least one reservoir and transmits the at least one analyte through the at least one conduit; and

the at least one detector is in association with the at least one conduit to detect the at least one analyte transmitted through the at least one conduit.

139. The device of claim 137, wherein said at least one sampler unit body further comprises means for enhancing permeability of the skin of a subject for retrieving said at least one analyte therefrom.

140. The device of claim 139, wherein said means for enhancing permeability comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface, and configured for ablating a portion of the stratum corneum of the skin of a subject to allow collection of interstitial fluid from the subject'"'"'s underlying viable epidermis.

141. The device of claim 139, wherein said means for enhancing permeability of the skin comprises a radiation source positioned for generating and directing radiation to a subject'"'"'s skin surface, effective to ablate a portion of the stratum corneum of the skin of a subject, to allow diffusion of interstitial fluid from the subject'"'"'s underlying viable epidermis.

142. The device of claim 141, wherein said radiation source is a light source.

143. The device of claim 142, wherein said light source is a laser.

144. The device of claim 139, wherein said means for enhancing permeability of the skin is at least one of;

(i) means for chemically altering the surface of the skin, (ii) means for puncturing the surface of the skin, (iii) means for solubilizing the surface of the skin, (iv) means for illuminating the surface of the skin sufficient to cause ablation thereof, and (v) means for irradiating the surface of the skin to cause ablation thereof.

145. The device of claim 137, wherein said at least one sampler unit body comprises a plurality of sampling conduits;

and said at least one detector system comprises a plurality of detector systems.

148. The device of claim 138, wherein said at least one reservoir contains a fluid and transmits the fluid to a subject'"'"'s skin and to the at least one conduit.

149. The device of claim 148, wherein said fluid contained in said at least one reservoir permeates a subject'"'"'s skin.

150. The device of claim 148, wherein the reservoir retains the fluid in the reservoir with a breakable seal, wherein the breaking of the breakable seal releases the fluid.

151. The device of claim 137, wherein the sampler unit body substantially adheres to the skin of a subject.

152. The device of claim 137, further comprising at least one substance located in said sampler unit body which is capable of binding an analyte of interest, and said substance being detectable by said at least one detector system.

153. The device of claim 137, wherein said at least one detector system comprises a patch sensitive to at least one analyte for changing color in response to contact with said at least one analyte, positioned for contact with said at least one analyte, and at least one detector positioned for detecting a change in color of the patch.

154. The device of claim 137, wherein said sampler unit body is a silicon body having an array of capillary conduits extending therethrough for sampling analyte from the skin of a subject through said capillary conduits;

and at least one detector chamber associated with said at least one detection system, and in communication with said capillary conduits for detecting analytes received within the capillary chamber.

155. The device of claim 154, wherein said sampler unit body further comprises means for enhancing permeability of the skin of a subject for retrieving said at least one analyte therefrom.

156. The device of claim 155, wherein said means for enhancing permeability comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface, and configured for ablating a portion of the stratum corneum of the skin of a subject to allow collection of interstitial fluid from the subject'"'"'s underlying viable epidermis.

157. The device of claim 155, wherein said means for enhancing permeability comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface, and configured for ablating a portion of the stratum corneum of the skin of a subject to allow diffusion from interstitial fluid from the subject'"'"'s underlying viable epidermis.

158. The device of claim 155, wherein said means for enhancing permeability of the skin comprises a radiation source positioned for generating and directing radiation to a subject'"'"'s skin surface, effective to ablate a portion of the stratum corneum of the skin of a subject to allow collection of interstitial fluid from the subject'"'"'s underlying viable epidermis.

159. The device of claim 155, wherein said means for enhancing permeability of the skin comprises a radiation source positioned for generating and directing radiation to a subject'"'"'s skin surface, effective to ablate a portion of the stratum corneum of the skin of a subject to allow diffusion of interstitial fluid from the subject'"'"'s underlying viable epidermis.

160. The device of claim 159, wherein said radiation source is a light source.

161. The device of claim 160, wherein said light source is a laser.

162. The device of claim 155, wherein said means for enhancing permeability of the skin is at least one of;

(i) means for chemically altering the surface of the skin, (ii) means for puncturing the surface of the skin, (iii) means for solubilizing the surface of the skin, (iv) means for illuminating the surface of the skin sufficient to cause ablation thereof, and (v) means for irradiating the surface of the skin to cause ablation thereof.

163. The device of claim 155, wherein said at least one detector system comprises an optical detection system comprised of light sources effective to excite fluorophores, and at least one detector for detecting fluorescence from excited fluorophores.

164. The device of claim 163, wherein said light source comprises at least one LED or at least one laser.

165. The device of claim 155, wherein said silicon body comprises at least one reservoir in communication with said capillary conduits, wherein a fluid retained in the at least one reservoir transmits from the reservoir to the subject'"'"'s skin into at least one of the said capillary conduits.

166. The device of claim 165, wherein said silicon body further comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface at a location proximate to where said fluid is pumped into contact with the skin of a subject, wherein the microheater ablates a portion of the stratum corneum of the skin of a subject.

207. The transdermal sampling system according to claim 150, wherein the seal is semi-permeable or selectively permeable.

167. A microfabricated device for sampling analytes from the skin of a subject, comprising:

a detection chamber for receiving analytes retrieved from the skin of a subject, wherein the analytes are retrieved by a microfabricated device comprising a microfluidic assembly;

a photonic detection system, comprising a photonics source located attached to said microfabricated device in association with said detection chamber; and

at least one detector associated with said detection chamber for detecting analytes received in said detection chamber.

168. The device of claim 167, wherein said photonics source is at least one LED or at least one laser.

169. The device of claim 167, further comprising substances in said device which bind with selected analytes, and which fluoresce when said photonics source applies radiation thereto.

170. A microfabricated device for sampling analytes from the skin of a subject, comprising:

a detection chamber for receiving analytes retrieved from the skin of a subject, wherein the analytes are retrieved by a microfabricated device comprising a microfluidic assembly;

a patch which changes color when contacted by predetermined analytes, located attached to said microfabricated device in association with said detection chamber; and

detectors associated with said detection chamber, for detecting a change of color of the patch indicating the presence of a predetermined analyte.

171. A device for sampling and detecting analytes retrieved from the skin of a subject, comprising:

at least one microfluidic conduit for retrieving and transmitting an analyte from the skin of a subject to a detector, wherein the microfluidic conduit is a microfabricated device; and

means for enhancing permeability of the skin of a subject for retrieving said at least one analyte therefrom.

172. The device of claim 171, wherein said means for enhancing permeability comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface, and configured for ablating a portion of the stratum corneum of the skin of a subject to allow collection of interstitial fluid from the subject'"'"'s underlying viable epidermis.

173. The device of claim 171, wherein said means for enhancing permeability comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface, and configured for ablating a portion of the stratum corneum of the skin of a subject to allow diffusion from interstitial fluid from the subject'"'"'s underlying viable epidermis.

174. The device of claim 171, wherein said means for enhancing permeability of the skin comprises a radiation source positioned for generating and directing radiation to a subject'"'"'s skin surface, effective to ablate a portion of the stratum corneum of the skin of a subject, to allow collection of interstitial fluid from the subject'"'"'s underlying viable epidermis.

175. The device of claim 171, wherein said means for enhancing permeability of the skin comprises a radiation source positioned for generating and directing radiation to a subject'"'"'s skin surface, effective to ablate a portion of the stratum corneum of the skin of a subject, to allow diffusion from interstitial fluid from the subject'"'"'s underlying viable epidermis.

176. The device of claim 174, wherein said radiation source is a light source.

177. The device of claim 176, wherein said light source is a laser.

178. The device of claim 171, wherein said means for enhancing permeability of the skin is at least one of:

(i) means for chemically altering the surface of the skin;

(ii) means for puncturing the surface of the skin;

(iii) means for solubilizing the surface of the skin;

(iv) means for illuminating the surface of the skin sufficient to cause ablation thereof; and

(v) means for irradiating the surface of the skin to cause ablation thereof.

197. A method of biomedically monitoring a subject'"'"'s condition, the method comprising:

ablating a subject'"'"'s skin to allow interstitial fluid to perfuse therethrough;

collecting interstitial fluid from the subject'"'"'s ablated skin, using a microfabricated device comprising a microfluidic assembly; and

identifying and quantifying at least one type of selected molecules contained in the collected interstitial fluid.

198. The method of claim 197, wherein the at least one type of molecule is a metabolic marker of stress.

199. The method of claim 197, wherein the at least one type of molecule is at least one of an organophosphate, microbial toxin, inflammatory sequeli to microbial toxin, spore metabolite, prealbumin, C-reactive protein, troponin I, estrogen, and testosterone.

200. The method of claim 197, further comprising monitoring at least one of the subject'"'"'s vital physiologically statistics.

201. The method of claim 200, wherein said at least one of the subject'"'"'s vital physiological statistics comprises at least one of body temperature, pulse rate, blood pressure, and heart activity.

202. The method of claim 197, further comprising monitoring and detecting environmental conditions in which the subject is located.

203. The method of claim 197, wherein said identifying and quantifying comprises transferring said at least one type of molecule to a patch which changes color when in contact with said at least one type of molecule, and detecting a change in color of the patch.

204. The method of claim 197, wherein said identifying and quantifying comprises binding the at least one type of molecule with a second type of molecule which fluoresces when irradiated, irradiating the at least one type of molecule bound to the second type of molecule, and detecting any resultant fluorescence.

205. The method of claim 204, wherein the source for irradiating is a laser or an LED.