Enhanced analyte access through epithelial tissue
Inventors
Heikenfeld, Jason Charles • Jajack, Andrew • BROTHERS, Michael Charles
Assignees
University of Cincinnati • Epicore Biosystems Inc
Publication Number
US-10471249-B2
Publication Date
2019-11-12
Expiration Date
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
A device for increasing a concentration of at least one analyte in an advective flow of biofluid includes an agent for enhancing a paracellular permeability of an epithelial tissue; and an iontophoresis electrode and a counter electrode, which are adapted to increase the concentration of said analyte in the advective flow of the biofluid. A method of sensing an analyte in a biofluid includes increasing a paracellular permeability of an epithelial tissue layer; and inducing electro-osmotic flow by reverse iontophoresis to increase a concentration of said analyte in an advective flow of the biofluid, wherein said advective flow is driven by at least one of saliva generation, sweat generation, or reverse iontophoresis.
Core Innovation
Embodiments of the disclosed invention function to increase the concentration of analytes in biofluids by increasing the paracellular permeability of the epithelial barrier using at least one paracellular-permeability-enhancing agent. The invention includes an agent for enhancing a paracellular permeability of an epithelial tissue and an iontophoresis electrode and a counter electrode, which are adapted to increase the concentration of said analyte in the advective flow of the biofluid. In another embodiment, analyte-rich interstitial fluid can be actively flowed into the secreted biofluid via electro-osmotic flow induced by reverse iontophoresis. The advective flow is driven by at least one of saliva generation, sweat generation, or reverse iontophoresis.
The background identifies that current wearable biosensors are limited in the data they collect and that blood is the gold standard for measuring biochemistry but requires invasive sampling. Other biofluids such as sweat, saliva, and tears can be non-invasively measured but contain analytes at more dilute concentrations compared to blood and interstitial fluid. Epithelial tissue separates biofluids from blood and ISF and the tight junctions in the paracellular pathway reduce effective concentrations observed in the secreted biofluid by at least 10× and more often 100 to 1000× or greater. Therefore, enhancing paracellular permeability and using electro-osmotic flow can improve extraction of analytes from blood and ISF into non-invasively accessible biofluids for sensing.
Claims Coverage
Overview: one independent claim is present and it discloses three main inventive features related to agent delivery, electrically driven transport, and fluid collection.
Paracellular-permeability-enhancing agent
An agent for enhancing a paracellular permeability of a device wearer's epithelial tissue.
Iontophoresis and reverse iontophoresis electrodes configured to increase analyte concentration
An iontophoresis electrode and a counter electrode, which are configured to increase the concentration of at least one analyte in a biofluid by the following: using iontophoresis to transport the agent into the epithelial tissue, and using reverse iontophoresis to at least partially cause an advective flow of the biofluid from the epithelial tissue into the device.
Collector for transporting biofluid
A collector for transporting the biofluid from the epithelial tissue into the device.
The independent claim covers a combination of a paracellular-permeability-enhancing agent, electrodes configured for iontophoretic delivery and reverse-iontophoretic advective flow to increase analyte concentration, and a collector to transport the resulting biofluid into the device.
Stated Advantages
Increase the concentration of analytes in biofluids to improve measurement of target analyte(s).
Improve the detection of previously hard-to-detect analytes, making non-invasive biosensing a more viable option for health monitoring.
Enable extraction of analytes from blood and interstitial fluid into non-invasively accessible biofluids (e.g., sweat, saliva, tears) for sensing.
Facilitate continuous, real-time sensing by increasing analyte access through epithelial tissue and by combining paracellular permeability enhancement with electro-osmotic flow.
Documented Applications
Non-invasive wearable biosensors for continuous biochemical monitoring using sweat, saliva, or tears as biofluids.
Devices for delivering paracellular-permeability-enhancing agents topically or via iontophoresis to epithelia including the epidermis, sweat gland epithelium, and oral mucosa to enhance analyte extraction.
Devices that induce reverse-iontophoresis-induced electro-osmotic flow to drive analytes from blood and interstitial fluid into an advective flow of biofluid for sensing (e.g., sweat sensing, saliva sensing).
Devices that combine agent delivery, reverse iontophoresis, and analyte-specific sensors to collect and continuously sense analyte-rich biofluid in real time or collect biofluid for later analysis.
Interested in licensing this patent?