Massachusetts Institute of Technology

University of California

Uwe Pliquett

James C Weaver

Robert Samuel Langer

Mark R Prausnitz

Thomas E Zewert

Rita Vanbever

Joseph Kost

Samir Suresh Mitragotri

Richard H Guy

Christopher Cullander

Timothy Vaughan

Tani Chen

Thiruvallur R Gowrishankar

A method for measuring biopotential of an organism includes electroporating a portion of a tissue surface of the organism. The biopotential of the organism is then measured with electrodes at the electroporated portion of the organism. The portion of the organism that is electroporated can be, for example, a skin surface of the organism. A resistance-decreasing agent, such as heparin, sodium thiosulfate, thioglycolic acid solution and dithioglycolic acid can be applied to the tissue surface to facilitate reduction in electrical resistance. Another example of a resistance-decreasing agent is a keratin-disrupting agent, such as sulforhodamine. Examples of suitable biopotential measurements include electrocardiographic, electroencephalographic, electromyographic, electrohysterographic and elctrokymographic measurements. The method decreases skin resistance to diminish unwanted electrical voltages that compete with biopotential measurements, thereby significantly improving the biopotential measurement.

Biopotential measurement including electroporation of tissue surface

Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by application of an electric field, for example, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field.

Effect of electric field and ultrasound for transdermal drug delivery

The present invention relates to an apparatus and method for localized electroporation of tissue. An apparatus includes a perforate electrically insulating layer, a first electrode at a first side of the perforate electrically insulating layer and a second electrode at a second side of the perforate electrically insulating layer. An electric field extending between the first and second electrodes will preferentially extend through perforations of the electrically insulating layer. The electric field thereby causes electroporation of tissue that is proximate to the first electrode and is partitioned from the electrically insulating layer and the second electrode by the first electrode. The apparatus controllably limits the depth of the electric field within a tissue, such as skin, thereby electroporating a surface layer, such as a stratum corneum layer of the skin, without stimulating submerged nerve endings within the skin. Sensation of the applied voltage and especially pain sensation can thereby be controlled by the invention.

Apparatus and method for electroporation of tissue

A method of modifying epidermis for transport of a material by electroporation includes applying to epidermis an agent that, upon entry into the epidermis, will modify the epidermis to thereby cause and altered rate of transport of a material across the epidermis. Typically, the altered rate will be an increased rate of transport. The epidermis is electroporated, whereby at least a portion of the modifying agent enters the electroporated epidermis, thereby modifying the epidermis to cause an altered rate of transport of a material across the epidermis. In another embodiment, the modifying agent can modify the epidermis to enable measurement and/or monitoring of physiological conditions or change within or beneath the epidermis. The modifying agents can also be employed to facilitate discharge of fluids from within an organism, such as by providing pathways for discharge of fluids from a tumor. Examples of modifying agents include: oxidizing agents; reducing agents; particles, such as optical indicator beads or beads that include drugs to be released into tissue; electrically-charged particles or molecules; etc. Materials that can be transported by the method of the invention include, for example, proteins, nucleic acids, electrically charged molecules or particles, microorganisms suitable for immunization, etc. Also, tissues other than skin can be employed in the method of the invention.

Introduction of modifying agents into skin by electroporation

A method for delivering a nucleotide into an organism includes applying a composition which includes a nucleotide component to epidermis of the organism. The epidermis is electroporated, whereby at least a portion of the composition enters or passes across the epidermis, thereby delivering the nucleotide into the organism. An example of a suitable nucleotide which can be delivered by the method of the invention includes antisense oligodeoxynucleotides for treatment of melanomas.

Delivery of nucleotides into organisms by electroporation

A method is disclosed for treating tissue in response to a stimulus generated by the tissue. In one embodiment, the method transdermally treats an organism in response to a stimulus. In this embodiment, the medication is applied to epidermis of the organism, and the epidermis is electroporated in response to a stimulus, whereby the medication passes through the epidermis at a rate sufficient to alter the stimulus, thereby transdermally treating the organism. In another embodiment, the method measures a blood component content of blood. A portion of epidermis is electroporated to cause an aqueous fluid to be directed through an electroporated epidermis to a surface of the epidermis. Thereafter, the blood component content of the aqueous fluid is measured for correlation with a known aqueous fluid blood component content associated with a known concentration of blood component in the blood. The blood component concentration of the blood can thereby be measured. In still another embodiment, the method includes directing a medication to the tissue which can alter the stimulus when the tissue is electroporated, and electroporating the tissue in response to a stimulus, whereby the medication passes through the tissue in an amount sufficient to alter the stimulus, thereby treating the organism.

Growing community of inventors

Leipzig, Germany

Uwe Pliquett