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Byagathvalli, G.

Publications and source records attributed to Byagathvalli, G..

3 recordsLinked to original sources

A piezoelectric electroporator (Piezopen) for enhanced ''naked'' RNA vaccine delivery

Despite the success of COVID-19 mRNA vaccines, they still face challenges with high costs, complex manufacturing, off-target biodistribution, and systemic reactogenicity stemming from their inflammatory carriers: lipid nanoparticles (LNPs). While "naked" RNA delivery could in principle solve these issues, studies have suggested that it is infeasible due to rapid degradation by RNases and poor cellular entry, thereby necessitating formulations that enhance intracellular delivery and RNA stability. Now, we challenge this paradigm by showing that a simple and inexpensive (<$1), lighter-derived electroporator with microneedle electrodes (Piezopen) can augment gene expression and immunogenicity to naked mRNA leading to comparable responses to LNPs at low doses. We achieve robust responses in the absence of systemic inflammation and reactogenicity using skin-targeted delivery, administer diverse construct types (i.e., mRNA, self-amplifying RNA (saRNA), circular RNA (circRNA)), and demonstrate cross-species validation in live human skin to derisk subsequent clinical application. Our results introduce Piezopen as an inexpensive, well-tolerated, and efficacious alternative to LNPs for mRNA vaccine delivery, designed to facilitate routine vaccinations and pandemic response.

bioengineering↗

A 3D-printed hand-powered centrifuge for molecular biology

The centrifuge is an essential tool for many aspects of research and medical diagnostics. However, conventional centrifuges are often inaccessible outside of conventional laboratory settings, such as remote field sites, require a constant external power source, and can be prohibitively costly in resource-limited settings and STEM-focused programs. Here we present the 3D-Fuge, a 3D-printed hand-powered centrifuge, as a novel alternative to standard benchtop centrifuges. Based on the design principles of a paper-based centrifuge, this 3D-printed instrument increases the volume capacity to 2 mL and can reach hand-powered centrifugation speeds up to 6,000 rpm. The 3D-Fuge devices presented here are capable of centrifugation of a wide variety of different solutions such as spinning down samples for biomarker applications and performing nucleotide extractions as part of a portable molecular lab setup. We introduce the design and proof-of-principle trials that demonstrate the utility of low-cost 3D printed centrifuges for use in remote and educational settings.

bioengineering↗

ElectroPen: An ultralow-cost piezoelectric electroporator

Electroporation is a basic yet powerful method for delivering small molecules (RNA, DNA, drugs) across cell membranes by application of an electrical field. Due to its vital role, electroporation has wide applicability from genetically engineering cells, to drug- and DNA-based vaccine delivery. Despite its broad applications in biological research, the high cost of electroporators is an obstacle for many budget-conscious laboratories. To address this need, we describe a simple, inexpensive, and hand-held electroporator inspired by a common household piezoelectric gas lighter. The proposed \"ElectroPen\" device costs about 20 cents, is portable (13 g), is fabricated on-demand using 3D-printing, and delivers repeatable exponentially decaying pulses of about 2000 V in 5 ms. We provide a proof-of-concept demonstration by genetically transforming plasmids into E. coli strains and show comparable transformation efficiency and cell growth with commercial devices, but at a fraction of the cost. Our results are validated by an independent team across the globe, providing a real-world example of democratizing science through frugal tools. Thus, the simplicity, accessibility, and affordability of our device holds potential for making modern synthetic biology accessible in high-school, community, and field-ecology laboratories.

bioengineering↗