Biology subjects

Manna, R.

Publications and source records attributed to Manna, R..

7 recordsLinked to original sources

bioRxiv2026

Machine Learning-Based Early Prediction of Neural Microelectrode Lifetime Under Accelerated Aging Conditions

Objective. Chronically implantable medical devices may require functional lifetimes of decades in order to reduce or eliminate the need for their explantation and replacement, which may involve invasive and sometimes risky surgery. However, when devices become exceptionally long-lived, preclinical studies validating their lifetimes become difficult to execute within reasonable timeframes even when accelerated life testing methods are employed. Computational methods capable of accurately and reliably predicting microelectrode lifetime from early-life data could therefore considerably expedite the development of long-lived implantable devices. Approach. Here, inspired by similar studies predicting functional lifetimes of lithium-ion battery cells from early-life data, we developed a machine learning model based on Elastic Net regression and early-life feature engineering to predict impedance-defined microelectrode lifetimes under accelerated aging conditions and evaluated its predictive performance. We also provide a dataset of electrochemical measurements from aging microelectrodes for public use. Main results. Using measurements collected through Day 5, the 10-feature Elastic Net model achieved a root mean squared error of 3.71 accelerated-aging days and a mean absolute percentage error of 13.90% under device-level validation. In an independent fabrication batch, covariance alignment and calibration using five labeled channels from one device in each target group reduced mean absolute percentage errors from 38.1% to 22.5% for Small electrodes and from 56.6% to 18.2% for Medium electrodes. Significance. These results highlight the potential of machine learning-based approaches to accurately predict neural microelectrode lifetimes from early-life data. Such methods may inform the design of future accelerated life studies, providing meaningful longevity estimates from shorter testing periods and potentially accelerating the development of long-lived implantable devices for clinical use.

bioengineering↗

bioRxiv2026

End-to-end automation of behavioural experiments with a collaborative robot

Reliable behavioural measurement is critical to neuroscience discovery, but end-to-end automation of experiments using live animals is challenging. Preparation and transfer of live animals into and out of behavioural assays require skilled, dexterous, gentle and consistent handling. This is difficult to achieve without bespoke automation systems, which resist wide adoption. We present STELA, a robotic cell featuring off-the-shelf collaborative robot (cobot) that autonomously runs the complete workflow of a Drosophila behaviour experiment, from vial to data. Designed to emulate human routine fly laboratory procedures in human workspace, it performs manipulation of fly culture vials, CO2 fly anaesthesia, vision-guided sex classification, single live fly manipulation, and loading and disassembly of a behaviour assay, all in a programmed loop. In 24-h working day, STELA completed 16 experiments (1024 individual visual learning assays in flies) compared to the human who, in an 8-hour working day, completed 6 (384 assays). Retention of flies fit for analysis was similar (93.85% versus 83.33%, respectively), but with 12-fold improvement in handling consistency by the robot. In biologically matched behaviour experiments, robotic and manual handling resulted in the same mean fly behavioural outcomes, yet the robot significantly reduced inter-individual variability in baseline and learning behaviours. STELA demonstrates that it is possible to deploy standard robotic systems to flexibly automate one of the most challenging animal experiments. It provides a low-variance, high-throughput platform for scalable experimentation, and a path to closed-loop, democratized robotic acceleration of experimental discovery.

animal behavior and cognition↗

bioRxiv2026

Long-Lasting Electrohydrodynamically Printed Transparent Soft Microelectrode for Implantable Biointerfaces

Reliable and scalable soft implantable neural interface fabrication remains a key challenge for chronic bioelectronic applications. Here, we present a transparent soft microelectrode fabricated with electrohydrodynamic (EHD) printing, utilizing the fluorinated polymer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS) to form seamless, selectively patterned multilayer structures with low impedance and long-term stability. Controlled in situ curing during printing yields dense, void-free substrate and encapsulation layers, suppressing interfacial defects and ionic pathways, while maintaining high optical transparency (>60%) with PEDOT:PSS. The printed microelectrodes exhibit low impedance, high charge storage and injection capacities, and stable electrochemical behavior under biomimetic conditions. In addition, the devices demonstrate robust mechanical and electromechanical stability under cyclic deformation in both dry and wet environments, as well as under prolonged electrical stimulation. Accelerated aging studies project multi-year operational lifetimes, and in vitro/in vivo biocompatibility assessments confirm excellent tissue integration. These results establish EHD-printed fluorinated polymer-based microelectrodes as a scalable and durable platform for chronic implantable biointerfaces. ToC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/726391v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@f4f717org.highwire.dtl.DTLVardef@8a34a1org.highwire.dtl.DTLVardef@185540dorg.highwire.dtl.DTLVardef@51462a_HPS_FORMAT_FIGEXP M_FIG C_FIG This report presents an electrohydrodynamically printed transparent soft microelectrode for chronic purposes. Electrohydrodynamic printing promotes seamless multilayer structures with selective deposition and long-term mechanical stability. The devices show low impedance, high charge capacity, and robust electrochemical/electromechanical properties. Accelerated aging projects [~]7.2 year lifetimes, and XPS/SEM-EDS confirm strong ion barrier properties and biocompatibility for chronic implantation.

bioengineering↗

bioRxiv2025

Promoter evolution in HIV-1C establishes latent reservoirs highly resistant to reversal

Latent viral reservoirs remain a major barrier to curing HIV-1, with the long-terminal repeat (LTR) and Tat playing crucial roles in regulating viral transcription. Subtype-specific transcription factor binding site (TFBS) variations within the LTR significantly influence latency and reservoir stability. In earlier work, we identified HIV-1C LTR variants with duplicated TFBS motifs, including NF-{kappa}B, AP1, RBEIII, and TCF-1/LEF-1. Using five cell models, including Jurkat and primary CD4 T cells, we compared canonical R-LTR and variant R2-LTR strains. Across sub-genomic reporters, single-round infections, and full-length viral vectors, we found that the balance between RBEIII and NF-{kappa}B motifs governs stability of latency. The two-viruses-one-cell system that normalized confounding environmental factors further revealed that latency is primarily controlled by intrinsic transcriptional circuits rather than external stimuli. In longitudinal studies of HIV-1 individuals from acute and chronic infection phases, we observed dominant R strains during early infection and the spontaneous emergence of R2 strains in nearly half of chronic-phase subjects, a process accelerated by ART. Upon CD4 T cell activation, R strains preferentially rebounded, while R2 strains showed strong resistance to reversal, even in subjects harbouring a co-infection. Together, these findings establish the clinical significance of LTR variation in latency regulation and identify the R2 phenotype as a critical determinant of reservoir persistence. These results underscore the importance of addressing reservoir heterogeneity in cure strategies, particularly in HIV-1C-prevalent regions.

microbiology↗

bioRxiv2024

Behavioral individuality is a consequence of experience, genetics and learning

Learning and memory are essential components of our individuality. While it is established that behaviour can vary across genetically identical individuals, it remains unknown how much of this variation stems from momentary experience during learning compared to genetics and its past interactions with the environment. To address this, we measured behaviour in thousands of flies from 90 genetic backgrounds while they performed tasks in conditions that either did or did not require learning. Flies that were genetically identical, raised under the same conditions and tested simultaneously in the same environment persistently modified the extent of expressed individuality when they could learn. This learning-induced residual expression of individuality and its dynamics were subdued or absent in innate, learning-independent behaviours. We could quantify and then recreate this phenomenon in computer simulations. The emergence of in silico behavioural individuality was most consistent with the individuality of real flies once we enabled reinforced learning in simulated agents. Moreover, we showed that minor differences in initial conditions of the experiment can exacerbate the expression of individuality within a genotype in a learning-dependent manner. Our results establish that besides the classical G x E interactions shared between individuals in the past, learning from individual momentary experience further extends the expression of individuality.

animal behavior and cognition↗

bioRxiv2023

Pump-free and high-throughput generation of monodisperse hydrogel beads by microfluidic step emulsification for dLAMP-on-a-chip

Step emulsification (SE), which generates droplets by a sharp change in confinement, has emerged as a potential alternative to flow-focusing technology. Water/dispersed phase is continuously pumped through a shallow inlet channel into a deep chamber pre-filled with the oil/continuous phase. The need for one or more pumps to maintain a continuous flow for droplet generation, and the consequent use of high sample volumes, limit this technique to research labs. Here, we report a pumpfree SE technique for rapid and high-throughput generation of monodisperse hydrogel (agarose) beads using <40 {micro}l sample volume. Instead of using syringe pumps, we sequentially pipetted oil and liquid agarose into a microfluidic SE device to generate between 20000 and 80000 agarose beads in [~] 2 min. We also demonstrated the encapsulation of loop-mediated isothermal amplification mixture inside these beads at the time of their formation. Finally, using these beads as reaction chambers, we amplified nucleic acids from P. falciparum and SARS-CoV-2 inside them. The pump-free operation, tiny sample volume, and high-throughput generation of droplets by SE make our technique suitable for point-of-care diagnostics.

bioengineering↗

bioRxiv2020

SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma

To investigate the evolution of SARS-CoV-2 in the immune population, we co-incubated authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for 7 passages, but after 45 days, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed at day 80 by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom and South Africa of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed. One Sentence SummaryThree mutations allowed SARS-CoV-2 to evade the polyclonal antibody response of a highly neutralizing COVID-19 convalescent plasma.

immunology↗