Department of Biomedical Engineering

Indian Institute of Technology Hyderabad (IITH) is a premier institute of science and technology established in 2008. IITH has been consistently ranked in the&nbsp;<a href="https://iith.ac.in/reports/" rel="noopener noreferrer">top 10 institutes</a>&nbsp;in India for Engineering&nbsp;<a href="https://www.nirfindia.org/2021/EngineeringRanking.html" rel="noopener noreferrer" target="_blank">according to NIRF</a>&nbsp;making it one of the most coveted schools for science and technology in the country.

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The very foundation of IIT Hyderabad is based on&nbsp;<a href="https://iith.ac.in/research/">research and innovation</a>. The vibrant research culture is evident from the number of patents and publications that IITH produces consistently every year. IITH offers&nbsp;<a href="https://iith.ac.in/academics/programmes-offered/">graduate programs</a>&nbsp;at both a masters, and a doctoral level, in several diverse areas. There are separate programs for technology, design, science, and liberal arts. The&nbsp;<a href="https://iith.ac.in/academics/post-graduate/">MTech program</a>&nbsp;is offered in various modes and durations to cater to the ever-growing need of postgraduate level professionals in the country.

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IIT Hyderabad

Deep Brain Stimulation (DBS) is an established and effective neuromodulation technique preferred in treating several neurological and neuropsychiatric disorders such as Parkinson's Disease(PD), epilepsy, obsessive compulsive disorder, depression and several such disorders. Magnetoencephalography (MEG) is a widely used neuroimaging strategy to understand the pathology and the therapeutic effects of DBS in clinical cohorts. One of the significant limitations is the inability to differentiate the DBS stimulation artefact from actual neuronal excitations, especially in lower frequency bands of interest where sub-harmonics of DBS artefacts may obscure the biological response and is a confounder. The primary objective of this study is to understand how DBS stimulation artefacts affect MEG signals and to this end, we employ a phantom based on a water melon. Using this phantom, we record the spectral signature of the DBS stimulation artefact at various DBS frequencies and stimulation voltages, the effect of standard artefact rejection approaches like spatiotemporal signal space separation (tSSS). We present in this paper the results of the initial analysis. © 2021 IEEE.

World University root node

2021 IEEE International Conference on Distributed Computing, VLSI, Electrical Circuits and Robotics, DISCOVER 2021 - Proceedings

How Does Deep Brain Stimulation Affect Magnetoencephalography Data?

We report a low cost Full-field Optical Coherence Tomography system for tissue demarcation to identify early morphological alteration of epithelial linings of the stomach. It can help to perform an accurate histological analyses non-invasively. © COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only.

Progress in Biomedical Optics and Imaging - Proceedings of SPIE

Full-field optical coherence tomography for optical biopsy applications

For treating cancer at various stages, chemotherapy drugs administered in combination provide better treatment results with lower side effects compared to single-drug therapy. However, finding the potential drug combinations has been challenging due to the large numbers of possible combinations from approved drugs and the failure of in vitro 2D well plate-based cancer models. 3D spheroid-based high-throughput microfluidic platforms recapitulate some of the important features of native tumor tissue and offer a promising alternative to evaluate the combinatory effects of the drugs. This study develops a novel polydimethylsiloxane (PDMS) based microfluidic design with a dynamic environment and strategically placed U-shaped wells for testing all seven possible combinations (three single-drug treatments, three pairwise combinations, treatment with all three drugs) of three chemotherapy drugs (Paclitaxel, Vinorelbine, and Etoposide) on lung tumor spheroids. The design of U-shaped wells has been validated with computational results. Firstly, we test all combinations of drugs on the conventional well plate in static conditions with 3D tumor spheroids. Based on static drug testing results, we show a proof-of-concept by testing the most effective drug combination on the microfluidic device in a dynamic environment. The concentration of the drugs used in combination falls below the maximum tolerated dose (MTD) of the individual drugs, towards low dose metronomic (LDM) chemotherapy. LDM combinatorial chemotherapy identified in this study can potentially lower toxicity and provide better treatment results in cancer patients. The device can be further used to culture patient-specific tumor spheroids and identify synergistic drug combinations for personalized medicine. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Department of Chemical Engineering

Biomedical Microdevices

A novel design of microfluidic platform for metronomic combinatorial chemotherapy drug screening based on 3D tumor spheroid model

A mesoionic N-heterocyclic carbene-gold(i) complex with a unique Au⋯H-C(methine) intramolecular hydrogen bonding interaction has been investigated in the solid state. The structure of this new neutral gold(i)-carbene was characterized by FT-IR and NMR spectroscopy, TGA, and X-ray diffraction techniques. Density functional theory (DFT) and atoms-in-molecule (AIM) analysis revealed that the gold-hydrogen bonding situation is more favored. Besides, the photophysical properties of the gold(i) complex were also investigated. This journal is © The Royal Society of Chemistry.

Department of Chemistry

Dalton Transactions

A gold(i) 1,2,3-triazolylidene complex featuring the interaction between gold and methine hydrogen

Acne is one of the common dermatological skin inflammatory conditions. The current therapeutic modalities for the treatment of acne include the administration of antibiotics and anti-inflammatory agents. The rising instance of antibiotic resistance in acne strains has led to the exploration of alternative therapeutic modalities. In the current study, we have employed a liposomal gold nanoparticle entrapping curcumin (Au Lipos Cur NPs) for dual light-mediated therapy for the treatment of acne. These nanoparticles exerted a positive zeta potential that enabled their localized follicular delivery by iontophoresis. The localized deposition of Au Lipos NPs leads to photothermal transduction causing destruction of sebaceous glands. Furthermore, when the nanoparticles were assessed in vitro by sequential irradiation with NIR and blue light, it resulted in significant inhibition of bacterial growth. Thus the dual light-mediated therapy by Au Lipos Cur NPs can form a potential therapeutic modality for the efficient treatment of recurrent acne. This journal is © The Royal Society of Chemistry.

Biomaterials Science

Iontophoresis mediated localized delivery of liposomal gold nanoparticles for photothermal and photodynamic therapy of acne

The most challenging phase in the clinical translation of drugs is the complex process of screening various drugs and evaluating their therapeutic effects in vitro and in vivo. Microfluidic models have been recognized as an interesting alternative to animal models for drug screening. Enhanced permeation and retention (EPR) effect is one of the most widely used standard for drug delivery in solid tumors with high vascular density and active angiogenesis. The nascent blood vessels in the tumor vicinity have large gaps between the endothelial junctions which allow nanoparticles to pass through them, resulting in selective extravasation and passive accumulation in the tumor regions. In this study, an attempt has been made to mimic some of the physiological characteristics in solid tumors such as endothelial gap junctions, obstructed blood vessels and EPR using a microfluidic platform for drug screening under dynamic culture conditions. The microfluidic chip was fabricated using soft lithography technique. Numerical simulations were performed to analyze the flow patterns inside the chip. Fluorescent gold nanoclusters (Au NCs) were synthesized and their accumulation in the tumor cells cultured inside the microfluidic chip was studied. The experimental results showed an increased uptake of Au NCs in the cells near the endothelial gap junctions in comparison to the cells away from the junctions. The observations in the study correlated with the leaky nature of the tumor vasculature, owing to the enhancement of vascularization and thereby EPR effect. Hence, the fabricated microfluidic device has the potential of minimizing the number of pre-clinical trials using animal models, allowing easier drug screening. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Microfluidics and Nanofluidics

Microfluidic design of tumor vasculature and nanoparticle uptake by cancer cells

Continuous monitoring of an electrocardiogram (ECG) in private diagnostic spaces such as vehicles or apartments allows early detection of cardiovascular diseases. We will use an armchair with integrated capacitive electrodes to record the capacitive electrocardiogram (cECG) during everyday activities. However, movements and other artifacts affect the signal quality. Therefore, an artifact index is needed to detect artifacts and classify the cECG. The unavailability of cECG data and reliable ground truth information requires new recordings to develop an artifact index. This study is designed to test the hypothesis: an artifact index can be devised, which intends to estimate the signal quality of segments and classify signals. In a single-arm study with 44 subjects, we will record two activities of 11-minute duration: reading and watching television. During recording, we will capture cECG, ECG, and oxygen saturation (SpO2) with time synchronization as well as keypoint-based movement indicators obtained from a video camera. SpO2 provides additional information on the subject’s health status. The keypoint-based movements indicate artifacts in the cECG. We will combine all ground truth data to evaluate the index. In the future, we aim at using the artifact index to exclude cECG segments with artifacts from further analysis. This will improve cECG technology for the measurement of cardiovascular parameters. Copyright: © 2021 Warnecke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Fulltext

PLoS ONE

Registered report protocol: Developing an artifact index for capacitive electrocardiography signals acquired with an armchair

Scientific Reports

Author Correction: Fabrication of microfluidic device for Aflatoxin M1 detection in milk samples with specific aptamers (Scientific Reports, (2020), 10, 1, (4627), 10.1038/s41598-020-60926-2)

The perfusion-based in vitro three-dimensional (3D) tumor models built on the microfluidic technology are leading the current research in tumor modeling for testing anticancer drugs/agents. The conventional two-dimensional in vitro and animal models used in preclinical drug development have many drawbacks. Tumor models based on the microfluidic principles and technology promise to overcome many of those drawbacks. The inclusion of physiological tumor parameters on a microscale chip is beneficial in obtaining precise tumor pathology and meaningful drug responses, which can aid in predicting human clinical drug outcomes. In this chapter, we mainly focus on the microphysiological models, which have a flow component in the device design, and their maturation toward highly complex multiorgan systems. The microfluidic tumor models incorporating pharmacokinetics and pharmacodynamics (PK/PD) of anticancer drugs are explained. Finally, we discuss the challenges involved in the determination of drug absorption, distribution, metabolism, excretion, and toxicity, along with the recently developed 3D microfluidic tumor models that can help acquire these data as per the mathematical PK/PD models. © 2020 Elsevier Inc. All rights reserved.

Biomaterials for 3D Tumor Modeling

Perfusion-based 3D tumor-on-chip devices for anticancer drug testing

There is a globally rising healthcare need to develop new anticancer therapies as well as to test them on biologically relevant in vitro cancer models instead of overly simplistic 2D models. To address both these needs, a 3D lung cancer spheroid model is developed using human A549 cells trapped inside a collagen gel in a compartmentalized microfluidic device and homogenously sized (35–45 µm) multicellular tumor spheroids are obtained in 5 days. The novel tryptophan-rich peptide P1, identified earlier as a potential anticancer peptide (ACP), shows enhanced cytotoxic efficacy against A549 tumor spheroids (>75%) in clinically relevant low concentrations, while it does not affect human amniotic membrane mesenchymal stem cells at the same concentrations (<15%). The peptide also inhibits the formation of tumor spheroids by reducing cell viability as well as lowering the proliferative capacity, which is confirmed by the expression of cell proliferation marker Ki-67. The ACP offers a novel therapeutic strategy against lung cancer cells without affecting healthy cells. The microfluidic device used is likely to be useful in helping develop models for several other cancer types to test new anticancer agents. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim