Soham Sinha

All Publications

• Scalable Human IPSC-to-3D Bioprinting Pipeline: Successful Large-Scale Production Using Automated Bioreactor Systems Ladi, R., Ho, D., Lee, S., Du, J., Weiss, J., Tam, T., Sinha, S., Klinger, D., Devine, S., Hamfeldt, A., Leng, H., Herrmann, J., He, M., Fradkin, L., Tan, T., Standish, D., Tomasello, P., Traul, D., Dianat, N., Vicard, Q., Katikireddy, K., Skylar-Scott, M. CELL PRESS. 2024: 640

  View details for Web of Science ID 001332783402271

• A Visual, In-Expensive, and Wireless Capillary Rheometer for Characterizing Wholly-Cellular Bioinks. Small (Weinheim an der Bergstrasse, Germany) Du, J., Lee, S., Sinha, S., Solberg, F. S., Ho, D. L., Sampson, J. P., Wang, Q., Tam, T., Skylar-Scott, M. A. 2023: e2304778

  Abstract

  Rheological measurements with in situ visualization can elucidate the microstructural origin of complex flow behaviors of an ink. However, existing commercial rheometers suffer from high costs, the need for dedicated facilities for microfabrication, a lack of design flexibility, and cabling that complicates operation in sterile or enclosed environments. To address these limitations, a low-cost ($300) visual, in-expensive and wireless rheometer (VIEWR) using 3D-printed and off-the-shelf components is presented. VIEWR measurements are validated by steady-state and transient flow responses for different complex fluids, and microstructural flow profiles and evolution of yield-planes are revealed via particle image velocimetry. Using the VIEWR, a wholly-cellular bioink system comprised of compacted cell aggregates is characterized, and complex yield-stress and viscoelastic responses are captured via concomitantly visualizing the spatiotemporal evolution of aggregate morphology. A symmetric hyperbolic extensional-flow geometry is further constructed inside a capillary tube using digital light processing. Such geometries allow for measuring the extensional viscosity at varying deformation rates and further visualizing the alignment and stretching of aggregates under external flow. Synchronized but asymmetric evolution of aggregate orientation and strain through the neck is visualized. Using varying geometries, the jamming and viscoelastic deformation of aggregates are shown to contribute to the extensional viscosity of the wholly-cellular bioinks.

  View details for DOI 10.1002/smll.202304778

  View details for PubMedID 38085139

• Large-Scale Production of Wholly-Cellular Bioinks via the Optimization of Human Induced Pluripotent Stem Cell Aggregate Culture in Automated Bioreactors. Advanced healthcare materials Ho, D. L., Lee, S., Du, J., Weiss, J. D., Tam, T., Sinha, S., Klinger, D., Devine, S., Hamfeldt, A., Leng, H. T., Herrmann, J. E., He, M., Fradkin, L. G., Tan, T. K., Traul, D., Vicard, Q., Katikireddy, K., Skylar-Scott, M. A. 2022: e2201138

  Abstract

  Combining the sustainable culture of billions of human cells and the bioprinting of wholly-cellular bioinks offers a pathway towards organ-scale tissue engineering. Traditional 2D culture methods are not inherently scalable due to cost, space, and handling constraints. Here, we optimize the suspension culture of human induced pluripotent stem cell-derived aggregates using an automated 250 mL stirred tank bioreactor system. Cell yield, aggregate morphology, and pluripotency marker expression are maintained over three serial passages in two distinct cell lines. Furthermore, we demonstrate that the same optimized parameters can be scaled to an automated 1 L stirred tank bioreactor system. Our 4-day culture resulted in a 16.6- to 20.4-fold expansion of cells, we generate approximately 4 billion cells per vessel, while maintaining > 94% expression of pluripotency markers. The pluripotent aggregates can be subsequently differentiated into derivatives of the three germ layers, including cardiac aggregates, and vascular, cortical and intestinal organoids. Finally, the aggregates are compacted into a wholly-cellular bioink for rheological characterization and 3D bioprinting. The printed hAs are subsequently differentiated into neuronal and vascular tissue. This work demonstrates an optimized suspension culture-to-3D bioprinting pipeline that enables a sustainable approach to billion cell-scale organ engineering. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/adhm.202201138

  View details for PubMedID 36314397

• LoCHAid: An ultra-low-cost hearing aid for age-related hearing loss PLOS ONE Sinha, S., Irani, U. D., Manchaiah, V., Bhamla, M. 2020; 15 (9): e0238922

  Abstract

  Hearing aids are the primary tool in non-medical rehabilitation for individuals with hearing loss. While the costs of the electronic components have reduced substantially, the cost of a hearing aid has risen steadily to the point that it has become unaffordable for the majority of the population with Age-Related Hearing Loss (ARHL) especially for those residing in low- and middle-income countries. Here, we present an ultra-low-cost, affordable and accessible hearing aid device ('LoCHAid'), specifically targeted towards treating ARHL in elderly patients. The LoCHAid components cost 98 cents (< $1) when purchased in bulk for 10,000 units and can be personalized for each user through a 3D-printable case. It is designed to be an over-the-counter (OTC) self-serviceable solution for elderly individuals with ARHL. Electroacoustic measurements show that the device meets most of the targets set out by the WHO Preferred Product Profile and Consumer Technology Association for hearing aids. The frequency response of the hearing aid shows selectable gain in the range of 4-8 kHz, and mild to moderate gain between 200-1000 Hz, and shows very limited total distortion (1%). Simulated gain measurements show that the LoCHAid is well fitted to a range of ARHL profiles for males and females between the ages of 60-79 years. Overall, the measurements show that the device offers the potential to benefit individuals with ARHL. Thus, our proposed design has the potential to address the challenge of affordable and accessible hearing technology for hearing impaired elderly individuals especially in low- and middle-income countries.

  View details for DOI 10.1371/journal.pone.0238922

  View details for Web of Science ID 000575688700022

  View details for PubMedID 32966301

  View details for PubMedCentralID PMC7510997

• ElectroPen: An ultra-low-cost, electricity-free, portable electroporator. PLoS biology Byagathvalli, G., Sinha, S., Zhang, Y., Styczynski, M. P., Standeven, J., Bhamla, M. S. 2020; 18 (1): e3000589

  Abstract

  Electroporation is a basic yet powerful method for delivering small molecules (RNA, DNA, drugs) across cell membranes by application of an electrical field. It is used for many diverse applications, from genetically engineering cells to drug- and DNA-based vaccine delivery. Despite this broad utility, the high cost of electroporators can keep this approach out of reach for many budget-conscious laboratories. To address this need, we develop a simple, inexpensive, and handheld electroporator inspired by and derived from a common household piezoelectric stove lighter. The proposed "ElectroPen" device can cost as little as 23 cents (US dollars) to manufacture, is portable (weighs 13 g and requires no electricity), can be easily fabricated using 3D printing, and delivers repeatable exponentially decaying pulses of about 2,000 V in 5 ms. We provide a proof-of-concept demonstration by genetically transforming plasmids into Escherichia coli cells, showing transformation efficiency comparable to commercial devices, but at a fraction of the cost. We also demonstrate the potential for rapid dissemination of this approach, with multiple research groups across the globe validating the ease of construction and functionality of our device, supporting the potential for democratization of 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 resource-poor laboratories.

  View details for DOI 10.1371/journal.pbio.3000589

  View details for PubMedID 31922526

  View details for PubMedCentralID PMC6953602

• A 3D-printed hand-powered centrifuge for molecular biology. PLoS biology Byagathvalli, G., Pomerantz, A., Sinha, S., Standeven, J., Bhamla, M. S. 2019; 17 (5): e3000251

  Abstract

  The centrifuge is an essential tool for many aspects of research and medical diagnostics. However, conventional centrifuges are often inaccessible outside of standard laboratory settings, such as remote field sites, because they require a constant external power source and can be prohibitively costly in resource-limited settings and Science, technology, engineering, and mathematics (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 field biology and educational settings.

  View details for DOI 10.1371/journal.pbio.3000251

  View details for PubMedID 31112539

  View details for PubMedCentralID PMC6528969