Bioluminescence as a sensitive electroporation indicator in sub-microsecond and microsecond range of electrical pulses

Novickij, Vitalij; Zinkevičienė, Auksė; Malyško, Veronika; Novickij, Jurij; Kulbacka, Julita; Rembiałkowska, Nina; Girkontaitė, Irutė

doi:10.1016/j.jphotobiol.2020.112066

Cited by 7 publications

(5 citation statements)

References 44 publications

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“…The threshold value for reversible electroporation depends on the duration of exposure to the electric field ( 11 ). For the millisecond-long pulses, the electroporation threshold is expected to be on the order of 400 V/cm to 600 V/cm ( 11 , 26 ), while, for the microsecond pulse duration (as in the ePatch), the threshold is increased to 1.0 kV/cm to 1.5 kV/cm ( 27 – 29 ). When simulating 300-V pulses like in the ePatch, the highest electric field strength in the tissue is 15 kV/cm immediately next to the electrodes, but most of the tissue experiences field strengths of 2 kV/cm to 3 kV/cm ( Fig.…”

Section: Resultsmentioning

confidence: 99%

An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination

Xia

Jin

Byagathvalli

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array (“ePatch”) for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin’s epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.

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Section: Resultsmentioning

confidence: 99%

An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination

Xia

Jin

Byagathvalli

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…When operating at field strengths ranging from 2 kV cm À1 to 3 kV cm À1 in microseconds, the device surpasses the threshold for millisecond electroporation, effectively enhancing the cellular immune response to DNA vaccines. 127 This straightforward ePatch device requires no additional power and significantly improves DNA vaccination efficiency, even reducing the required vaccine dosage by tenfold, as evidenced by experimental results. 90 The integration of ultrasound with MNs also offers a promising approach for targeted drug delivery.…”

Section: The Emn Devices For Drug Deliverymentioning

confidence: 87%

Emerging microelectronic microneedles (eMN) for biomedical applications

Zhou,

et al. 2024

J. Mater. Chem. C

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“…Due to the length of the microneedles, the electric field is limited to the epidermis and superficial dermis, thus avoiding stimulation of the sensory and motor nerves located deeper in the dermis or muscle tissue. The nominal electric field strength in the tissue targeted by ePatch is ~2000–3000 kV/cm, 32 similar to the electric field strength used for microsecond‐long electroporation pulses 37–39 . In a recent study, we showed that electroporation by ePatch elicited at least a 10‐fold dose‐sparing antibody response against SARS‐CoV‐2 compared to intramuscular or intradermal injections of a SARS‐CoV‐2 DNA vaccine in mice 32 …”

Section: Introductionmentioning

confidence: 85%

“…The nominal electric field strength in the tissue targeted by ePatch is ~2000–3000 kV/cm, 32 similar to the electric field strength used for microsecond‐long electroporation pulses. 37 , 38 , 39 In a recent study, we showed that electroporation by ePatch elicited at least a 10‐fold dose‐sparing antibody response against SARS‐CoV‐2 compared to intramuscular or intradermal injections of a SARS‐CoV‐2 DNA vaccine in mice. 32 …”

Section: Introductionmentioning

confidence: 99%

Tolerability of a piezoelectric microneedle electroporator in human subjects

Lu,

Rohilla,

Felner

et al. 2024

Bioengineering & Transla Med

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Electroporation, or the use of electric pulses to facilitate the intracellular delivery of DNA, RNA, and other molecules, is a well‐established technique, that has been demonstrated to significantly augment the immunogenicity of DNA/mRNA vaccines and therapeutics. However, the clinical translation of traditional electroporators has been limited due to high costs, large size, complex user operation, and poor tolerability in humans due to nerve stimulation. In prior work, we introduced ePatch: an ultra‐low‐cost, handheld, battery‐free electroporator employing a piezoelectric pulser coupled with a microneedle electrode array that showed enhanced immunogenic responses to an intradermal SARS‐CoV‐2 DNA vaccine in mice. The current study shifts focus from efficacy to tolerability, hypothesizing that ePatch's microneedle array, which localizes the electric field to the superficial skin strata, will minimize nerve stimulation and improve patient comfort. We tested this hypothesis in 14 healthy adults, monitoring pain and other potential adverse effects associated with electroporation. Compared to the insertion of a traditional hypodermic needle, the ePatch was less painful. Adverse effects such as pain, tenderness, erythema and swelling at the application sites were minimal, transient, and statistically indistinguishable between the experimental and placebo ePatch application, suggesting excellent tolerability towards electroporation. In summary, ePatch has a favorable tolerability profile in humans and offers the potential for the safe use of electroporation in a variety of clinical settings, including DNA and mRNA vaccination.

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Bioluminescence as a sensitive electroporation indicator in sub-microsecond and microsecond range of electrical pulses

Cited by 7 publications

References 44 publications

An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination

An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination

Emerging microelectronic microneedles (eMN) for biomedical applications

Tolerability of a piezoelectric microneedle electroporator in human subjects

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