Ramakrishnan Venkatasubramanian

University of Copenhagen

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Poras T. Balsara

The University of Texas at Dallas

Sujan K. Manohar

The University of Texas at Dallas

Anette Müllertz

University of Copenhagen

Thomas Rades

University of Copenhagen

Stine B. Bering

University of Copenhagen

Karoline Aasmul‐Olsen

University of Copenhagen

Georgia-Ioanna Nora

University of Copenhagen

Jacob Rune Jørgensen

University of Copenhagen

Vikas Paduvalli

Analog Devices (United States)

Sophie Strindberg

University of Copenhagen

Cooperative Institutions

University of Copenhagen

Technical University of Denmark

Danish National Research Foundation

The Velux Foundations

Aarhus University

Ørsted (Denmark)

Lund University

Aarhus University Hospital

The University of Texas at Dallas

Villum Fonden

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Bidirectional Single-Supply Level Shifter with Wide Voltage Range for Efficient Power Management

Sujan K. Manohar Vinod K. Somasundar Ramakrishnan Venkatasubramanian Poras T. Balsara

Level shifter circuits are used to interface multiple voltage islands in many modern ICs or Systems-on-Chip (SoCs). Single-supply level shifters are being used to reduce the power routing resources and minimize the routing congestion at the chip level. A single-supply bidirectional level shifter aimed at low voltage which offers a wide voltage range (SS-WVRLS) is designed using standard commercial 90nm CMOS process. The proposed level shifter uses analog and digital circuit techniques to provide full voltage shifting range for any combination of supply voltages (VDDIN = VDD,VDDIN <; VDD or VDDIN >; VDD) in any step size (paper shows 25mv step) with no requirement for special low-Vτ or high-V _τ devices, thus reducing the process cost. Post layout SPICE simulation comparison results show that proposed circuit is functional for full core supply voltage range (0.6V - 1.32V) compared to other published level shifters. The circuit was tested for robustness under process mismatch conditions by 1000 point global and local Monte Carlo simulations.

Logic level

Process corners

Spice

Robustness

10.1109/vlsid.2012.58

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Citations (6)

In Vitro, Ex Vivo and In Vivo Evaluation of Microcontainers for Oral Delivery of Insulin

Pharmaceutics (2020)

Jacob Rune Jørgensen Feiyang Yu Ramakrishnan Venkatasubramanian Line Hagner Nielsen Hanne Mørck Nielsen

Enhancing the oral bioavailability of peptides has received a lot of attention for decades but remains challenging, partly due to low intestinal membrane permeability. Combining a permeation enhancer (PE) with unidirectionally releasing microcontainers (MCs) has previously been shown to increase insulin permeation across Caco-2 cell monolayers. In the present work, this setup was further employed to compare three common PEs—sodium caprate (C10), sodium dodecyl sulfate (SDS), and lauroyl carnitine. The concept was also studied using porcine intestinal tissue with the inclusion of 70 kDa fluorescein isothiocyanate-dextran (FD70) as a pathogen marker. Moreover, a combined proteolysis and Caco-2 cell permeation setup was developed to investigate the effect of soybean trypsin inhibitor (STI) in the MCs. Lastly, in vivo performance of the MCs was tested in an oral gavage study in rats by monitoring blood glucose and insulin absorption. SDS proved to be the most potent PE without increasing the ex vivo uptake of FD70, while the implementation of STI further improved insulin permeation in the combined proteolysis Caco-2 cell setup. However, no insulin absorption in rats was observed upon oral gavage of MCs loaded with insulin, PE and STI. Post-mortem microscopic examination of their gastrointestinal tract indicated lack of intestinal retention and optimal orientation by the MCs, possibly precluding the potential advantage of unidirectional release.

Ex vivo

Sodium dodecyl sulfate

Caco-2

10.3390/pharmaceutics12010048

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Citations (24)

NEM relay based memory architectures for low power design

Ramakrishnan Venkatasubramanian Sujan K. Manohar Vikas Paduvalli Poras T. Balsara

Nano-electromechanical (NEM) relays are a promising class of emerging devices that exhibit zero leakage operation. This work proposes three new NEM relay based parallel readout memory bitcell architectures that have faster access time, and remove the reliability issues associated with previously reported serial readout architectures. Accurate Verilog-A models were developed based on published fabrication results of NEM relays operating at 1V with a nominal air gap of 5 - 10nm. Bitcell stability and access time analysis are performed for all the proposed architectures and the results are presented.

Verilog

Leakage (economics)

10.1109/nano.2012.6322087

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Combining lipid based drug delivery and amorphous solid dispersions for improved oral drug absorption of a poorly water-soluble drug

Journal of Controlled Release (2022)

Georgia-Ioanna Nora Ramakrishnan Venkatasubramanian Sophie Strindberg Scheyla Daniela Siqueira-Jørgensen Livia Pagano

Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the aim of enhancing physical stability, solubilization and absorption of the model drug ritonavir. Ritonavir was loaded at a concentration above its saturation solubility (Seq) in the SNEDDS (superSNEDDS, 250% of Seq). An ASD of ritonavir with polyvinylpyrrolidone-vinyl acetate copolymers (Kollidon® VA64) was prepared by ball milling. Relevant control formulations, which include conventional SNEDDS (90% of Seq), superSNEDDS with a physical mix of Kollidon® VA64 and ritonavir (superSNEDDS+PM) and an aqueous suspension of ritonavir were used. A pharmacokinetic (PK) study in rats was performed to assess the relative bioavailability of ritonavir after oral administration. This was followed by evaluating the formulations in a novel two-step in vitro lipolysis model simulating rat gastric and intestinal conditions. The addition of a ritonavir containing ASD to superSNEDDS increased the degree of supersaturation from 250% to 275% Seq in the superSNEDDS and the physical stability (absence of drug recrystallization) of the system from 48 h to 1 month under ambient conditions. The PK study in rats displayed significantly higher Cmax and AUC0-7h (3-fold increase) and faster Tmax for superSNEDDS+ASD compared to the conventional SNEDDS whilst containing 3 times less lipid than the latter. Furthermore, superSNEDDS+ASD were able to keep the drug solubilised during in vitro lipolysis to the same degree as the conventional SNEDDS. These findings suggest that dissolving an ASD in a superSNEDDS can contribute to the development of novel oral delivery systems with increased bioavailability for poorly water-soluble drugs.

Ritonavir

10.1016/j.jconrel.2022.06.057

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Citations (20)

Hybrid NEMS-CMOS DC-DC Converter for Improved Area and Power Efficiency

Sujan K. Manohar Ramakrishnan Venkatasubramanian Poras T. Balsara

Nano-electromechanical (NEM) relays are a promising class of emerging devices that exhibit zero leakage operation. Numerous end applications of NEM relay logic circuits have been proposed recently [1][2]. This work explores the usage of NEM relays in on-chip DC-DC converters. As a feasibility study of using NEMS in integrated power electronics, discontinuous conduction mode (DCM) buck regulator with specifications suitable for portable applications has been implemented in a NEMS-CMOS hybrid design and the results are compared against a standard commercial 0.35 μm CMOS implementation. R _on of the NEM relay switch is constant and is insensitive to the gate slew rate. This creates a paradigm shift in design of power switches. This coupled with infinite R _off offers significant area and power advantages over CMOS. Accurate Verilog-A models were developed based on published fabrication results of NEM relays [1] operating at 1V with a nominal air gap of 5-10nm. This work shows that NEMS-CMOS hybrid DC-DC converter has an area savings of 60V over CMOS and achieves 95% efficiency at max load condition (50mA).

Nanoelectromechanical systems

10.1109/vlsid.2012.74

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Citations (8)

Ultra low power high efficiency charge pump design using NEM relays

2022 IEEE 65th International Midwest Symposium on Circuits and Systems (MWSCAS) (2011)

Ramakrishnan Venkatasubramanian Sujan K. Manohar Poras T. Balsara

The zero leakage operation of Nano-electromechanical (NEM) relays make the device a promising candidate among emerging devices. Numerous end applications of NEM relay logic circuits have been proposed recently. This work explores the usage of NEM relays in on-chip power management circuits. R _on of the NEM relay switch is constant and is insensitive to the gate slew rate. This creates a paradigm shift in design of power switches. This coupled with infinite R _off offers significant area and power advantages over CMOS. Accurate Verilog-A models were developed based on published fabrication results of NEM relays operating at 1V with a nominal air gap of 5 - 10nm. As a feasibility study of using NEMS in integrated power electronics, a step-down charge pump with specifications suitable for audio power amplifier applications has been implemented and the results are compared against a standard commercial 65nm CMOS implementation. This work shows that NEM relay based charge pump has an area savings of 73X, power savings of 14X over CMOS and achieves 96:1% efficiency at max load condition (18mA).

Slew rate

10.1109/mwscas.2011.6026545

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Citations (5)

Design, evaluation, and in vitro–in vivo correlation of self-nanoemulsifying drug delivery systems to improve the oral absorption of exenatide

Journal of Controlled Release (2025)

Ramakrishnan Venkatasubramanian Passant M. Al-Maghrabi Oscar Alavi Tania Kjellerup Lind Philip Sassene

The ability to predict the absorption of exenatide (Ex), a GLP-1 analogue, after oral dosing to rats in self-nanoemulsifying drug delivery systems (SNEDDS), using in vitro methods, was assessed. Ex was complexed with soybean phosphatidylcholine (SPC) prior to loading into SNEDDS. A design of experiments (DoE) approach was employed to develop SNEDDS incorporating medium-chain triglycerides (MCT), medium-chain mono- and diglycerides (MGDG), Kolliphor® RH40, and monoacyl phosphatidylcholine. SNEDDS with higher proportions of MGDG and Kolliphor® RH40 demonstrated a 9-fold reduction in droplet size (230 to 26 nm), a 1.5-fold decrease in lipolysis (0.23 to 0.34 mmol of FFA), and a 2-fold enhancement in exenatide protection against proteolysis (73 % to 38 %) compared to those with higher MCT content. Permeability studies in Caco-2 cells showed that SNEDDS with higher proportion of MGDG displayed a 40-fold increase in apparent permeability of FD4, when compared to SNEDDS with higher proportion of MCT. An oral gavage study in rats revealed a 1.8-fold higher absorption of Ex in SNEDDS with a higher proportion of MGDG and Kolliphor®RH40 compared to SNEDDS with higher MCT. These results establish a clear in vitro-in vivo correlation, demonstrating that the selected in vitro methods effectively differentiated formulations with high and low absorption of exenatide after oral dosing in rats.

Ex vivo

10.1016/j.jconrel.2025.01.013

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Assessing acute colitis induced by dextran sulfate sodium in rats and its impact on gastrointestinal fluids

Drug Delivery and Translational Research (2023)

Mette Klitgaard Maja Nørgaard Kristensen Ramakrishnan Venkatasubramanian Priscila R. Guerra Jette Bredahl Jacobsen

10.1007/s13346-023-01313-y

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Citations (3)

Dairy-Derived Emulsifiers in Infant Formula Show Marginal Effects on the Plasma Lipid Profile and Brain Structure in Preterm Piglets Relative to Soy Lecithin

Nutrients (2021)

Nicole Lind Henriksen Karoline Aasmul‐Olsen Ramakrishnan Venkatasubramanian Mikkel Nygaard Richard R. Sprenger

Breastfed infants have higher intestinal lipid absorption and neurodevelopmental outcomes compared to formula-fed infants, which may relate to a different surface layer structure of fat globules in infant formula. This study investigated if dairy-derived emulsifiers increased lipid absorption and neurodevelopment relative to soy lecithin in newborn preterm piglets. Piglets received a formula diet containing soy lecithin (SL) or whey protein concentrate enriched in extracellular vesicles (WPC-A-EV) or phospholipids (WPC-PL) for 19 days. Both WPC-A-EV and WPC-PL emulsions, but not the intact diets, increased in vitro lipolysis compared to SL. The main differences of plasma lipidomics analysis were increased levels of some sphingolipids, and lipid molecules with odd-chain (17:1, 19:1, 19:3) as well as mono- and polyunsaturated fatty acyl chains (16:1, 20:1, 20:3) in the WPC-A-EV and WPC-PL groups and increased 18:2 fatty acyls in the SL group. Indirect monitoring of intestinal triacylglycerol absorption showed no differences between groups. Diffusor tensor imaging measurements of mean diffusivity in the hippocampus were lower for WPC-A-EV and WPC-PL groups compared to SL indicating improved hippocampal maturation. No differences in hippocampal lipid composition or short-term memory were observed between groups. In conclusion, emulsification of fat globules in infant formula with dairy-derived emulsifiers altered the plasma lipid profile and hippocampal tissue diffusivity but had limited effects on other absorptive and learning abilities relative to SL in preterm piglets.

10.3390/nu13030718

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Citations (12)

Energy efficient circuit design using nanoelectromechanical relays

PhDT (2012)

Ramakrishnan Venkatasubramanian

Nanoelectromechanical systems

Source

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Citations (1)