Appartus and method for continuous real-time trace biomolecular sampling, analysis, and delivery
Inventors
Currie, John Frederick • Paranjape, Makarand
Assignees
Cambridge Medical Technologies LLC
Publication Number
US-8364228-B2
Publication Date
2013-01-29
Expiration Date
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Abstract
A system and method for transdermal sampling wherein at least one pair of sample electrodes is adapted to provide voltage pulses capable of creating capillary openings in a subject's stratum corneum. Methods for using a transdermal sampling system by creating capillary openings in a subject's stratum corneum via the application of a series of voltage pulses to the stratum corneum and contacting at least a portion of at least one of the sample electrodes with interstitial fluid from the capillary openings are also presented.
Core Innovation
The invention is a system and method for transdermal sampling in which at least one pair of sample electrodes on a flexible substrate and an anchor layer are used to create capillary openings in a subject's stratum corneum by application of a sequence of electrical pulses, allowing interstitial fluid to contact the sample electrodes for continuous real-time trace biomolecular sampling and analysis. The trans-dermal platform in a preferred embodiment has a flexible substrate on which a pair of sample electrodes are joined by a resistive element, an electro-conducting enzyme anchor layer covering part of at least one of the sample electrodes, and a protective layer that may cover the platform except near the sample electrodes. Any target bio-molecule in the interstitial fluid drawn into the vicinity of the electro-conducting enzyme anchor layer interacts with the anchored enzyme and this interaction may be detected by electrochemical measurements.
The problem being solved is that prior transdermal sampling approaches typically make relatively large holes through the stratum corneum by ablation or puncture, producing local irritation and inflammation so channels cannot be maintained for extended periods, and prior device substrates such as silicon are relatively inflexible causing poor surface contact and loss of function with even small lateral motion. Because prior holes are typically tens of microns in diameter they cause irritation and cannot be maintained open for longer than a few hours to a few days, and complex micro-fabricated silicon systems are relatively inflexible making close surface contact difficult. To achieve minimally invasive, continuous real-time trace transdermal sampling, an improved system and method that overcomes these difficulties is needed.
The method of the invention disrupts the stratum corneum by applying a series of electrical pulses to create capillary openings between dead cells that wick interstitial fluid from the viable epidermis up to the sample electrodes so as to equilibrate and dynamically maintain equilibrium with interstitial fluid in underlying tissue for many hours. The device may include cavities and encapsulated materials for controlled chemical delivery at the sampling site and the same or separate electrodes may be prepared to selectively measure biochemical analytes or physico-chemical properties, with measurements being continuous in nature to track time variation of concentrations. [procedural detail omitted for safety]
Claims Coverage
The patent includes two independent claims. The following inventive features are extracted from those independent claims.
Flexible substrate with sample electrodes
A flexible substrate comprising at least one pair of sample electrodes disposed on the flexible substrate and first electrically conductive paths coupled to the at least one pair of sample electrodes.
Anchor layer on sample electrodes
An anchor layer covering at least a portion of at least one pair of sample electrodes.
Separate conductive paths and resistive element
A second pair of electrically conductive paths and at least one resistive element coupled to the second pair of electrically conductive paths disposed proximate to the at least one pair of sample electrodes.
Resistive element configured to thermally disrupt stratum corneum
The at least one resistive element is configured to provide a sequence of thermal heating to generate a temperature sufficient to disrupt stratum corneum cells without damaging the stratum corneum cells to allow interstitial fluid to pass through capillary openings and into contact with the at least one pair of sample electrodes.
Affixing the device to stratum corneum
Affixing a device for transdermal sampling to the stratum corneum layer of a subject, the device comprising the flexible substrate, at least one pair of sample electrodes, an anchor layer, first and second electrically conductive paths, and at least one resistive element disposed proximate to the sample electrodes.
Applying voltage pulses to generate thermal disruption
Applying voltage pulses to the at least one resistive element via the second pair of electrically conductive paths to generate a temperature sufficient to disrupt the stratum corneum cells so interstitial fluid contacts the at least one pair of sample electrodes. [procedural detail omitted for safety]
In summary, the independent claims cover a flexible transdermal sampling device having sample electrodes and an anchor layer, separate conductive paths including a resistive element disposed proximate to the electrodes that thermally disrupts the stratum corneum to allow interstitial fluid access, and a method of affixing that device and applying electrical pulses to effect the disruption.
Stated Advantages
Minimally invasive continuous real-time trace sampling of interstitial fluid from viable epidermis.
Ability to create capillary openings that wick interstitial fluid and maintain equilibrium with underlying tissue for many hours.
Selective electrochemical measurement of multiple biomolecules and physico-chemical properties at sampling points with continuous monitoring.
Controlled on‑command delivery of stored bio-chemicals and the ability to monitor efficacy and individual response in real time.
Compact, economical fabrication possibilities and higher packing densities when disruption electrodes are used for electrochemical measurements.
Increased electrical signal and reduced signal-to-noise ratio achievable by increasing effective electrode surface area or using nanomaterials.
Documented Applications
Monitoring viability and functionality of organs and tissues prepared and stored for surgical implantation.
Monitoring entire chemical panels for individuals, patients, or populations at risk.
Monitoring for critical care, shock, trauma and resuscitation.
Monitoring for chronic critical disease and for early detection of disease.
Monitoring for response to therapeutic treatment and quantifying individual efficacy and adverse reactions.
Gene therapy applications including scaling sampling site dimensions to analyze intracellular fluid and inject therapeutics into individual cells.
Analyzing previously collected biological fluids or environmental samples such as food, water, air, whole blood, urine, saliva, and chemical reactions by applying them to the sampling device.
Monitoring cell culture viability and metabolism, and monitoring precipitates, distillates, and filtered powders.
Point-of-care analysis such as immediate analysis of blood draws and continuous monitoring of air and water samples for chemical and biological contaminants.
Military monitoring of individuals (for example glucose and lactate monitoring of soldiers) and use as a critical care and triage instrument.
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