Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening

Microwell technology has revolutionized many aspects of in vitro cellular studies from 2D traditional cultures to 3D in vivo-like functional assays. However, existing lithography-based approaches are often costly and time-consuming. This study presents a rapid, low-cost prototyping method of CO[subs...

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Main Authors: Tu, Ting-Yuan, Wang, Zhe, Bai, Jing, Sun, Wei, Peng, Weng Kung, Huang, Ruby Yun-Ju, Thiery, Jean-Paul, Kamm, Roger Dale
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Wiley Blackwell 2015
Online Access:http://hdl.handle.net/1721.1/97505
https://orcid.org/0000-0002-7232-304X
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author Tu, Ting-Yuan
Wang, Zhe
Bai, Jing
Sun, Wei
Peng, Weng Kung
Huang, Ruby Yun-Ju
Thiery, Jean-Paul
Kamm, Roger Dale
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Tu, Ting-Yuan
Wang, Zhe
Bai, Jing
Sun, Wei
Peng, Weng Kung
Huang, Ruby Yun-Ju
Thiery, Jean-Paul
Kamm, Roger Dale
author_sort Tu, Ting-Yuan
collection MIT
description Microwell technology has revolutionized many aspects of in vitro cellular studies from 2D traditional cultures to 3D in vivo-like functional assays. However, existing lithography-based approaches are often costly and time-consuming. This study presents a rapid, low-cost prototyping method of CO[subscript 2] laser ablation of a conventional untreated culture dish to create concave microwells used for generating multicellular aggregates, which can be readily available for general laboratories. Polymethylmethacrylate (PMMA), polydimethylsiloxane (PDMS), and polystyrene (PS) microwells are investigated, and each produces distinctive microwell features. Among these three materials, PS cell culture dishes produce the optimal surface smoothness and roundness. A549 lung cancer cells are grown to form cancer aggregates of controllable size from ≈40 to ≈80 μm in PS microwells. Functional assays of spheroids are performed to study migration on 2D substrates and in 3D hydrogel conditions as a step towards recapitulating the dissemination of cancer cells. Preclinical anti-cancer drug screening is investigated and reveals considerable differences between 2D and 3D conditions, indicating the importance of assay type as well as the utility of the present approach.
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spelling mit-1721.1/975052022-09-28T16:37:42Z Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening Tu, Ting-Yuan Wang, Zhe Bai, Jing Sun, Wei Peng, Weng Kung Huang, Ruby Yun-Ju Thiery, Jean-Paul Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Program in Comparative Media Studies/Writing Kamm, Roger Dale Microwell technology has revolutionized many aspects of in vitro cellular studies from 2D traditional cultures to 3D in vivo-like functional assays. However, existing lithography-based approaches are often costly and time-consuming. This study presents a rapid, low-cost prototyping method of CO[subscript 2] laser ablation of a conventional untreated culture dish to create concave microwells used for generating multicellular aggregates, which can be readily available for general laboratories. Polymethylmethacrylate (PMMA), polydimethylsiloxane (PDMS), and polystyrene (PS) microwells are investigated, and each produces distinctive microwell features. Among these three materials, PS cell culture dishes produce the optimal surface smoothness and roundness. A549 lung cancer cells are grown to form cancer aggregates of controllable size from ≈40 to ≈80 μm in PS microwells. Functional assays of spheroids are performed to study migration on 2D substrates and in 3D hydrogel conditions as a step towards recapitulating the dissemination of cancer cells. Preclinical anti-cancer drug screening is investigated and reveals considerable differences between 2D and 3D conditions, indicating the importance of assay type as well as the utility of the present approach. Singapore-MIT Alliance for Research and Technology Mechanobiology Institute, Singapore 2015-06-22T18:21:45Z 2015-06-22T18:21:45Z 2013-08 2013-07 Article http://purl.org/eprint/type/JournalArticle 21922640 http://hdl.handle.net/1721.1/97505 Tu, Ting-Yuan, Zhe Wang, Jing Bai, Wei Sun, Weng Kung Peng, Ruby Yun-Ju Huang, Jean-Paul Thiery, and Roger D. Kamm. “Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening.” Advanced Healthcare Materials 3, no. 4 (August 27, 2013): 609–616. https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1002/adhm.201300151 Advanced Healthcare Materials Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC
spellingShingle Tu, Ting-Yuan
Wang, Zhe
Bai, Jing
Sun, Wei
Peng, Weng Kung
Huang, Ruby Yun-Ju
Thiery, Jean-Paul
Kamm, Roger Dale
Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening
title Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening
title_full Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening
title_fullStr Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening
title_full_unstemmed Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening
title_short Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening
title_sort rapid prototyping of concave microwells for the formation of 3d multicellular cancer aggregates for drug screening
url http://hdl.handle.net/1721.1/97505
https://orcid.org/0000-0002-7232-304X
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