A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications

Duc T.T. Phan, Xiaolin Wang, Brianna M. Craver, Agua Sobrino, Da Zhao, Jerry C. Chen, Lilian Y.N. Lee, Steven George, Abraham P. Lee, Christopher C.W. Hughes

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

There is a growing awareness that complex 3-dimensional (3D) organs are not well represented by monolayers of a single cell type-the standard format for many drug screens. To address this deficiency, and with the goal of improving screens so that drugs with good efficacy and low toxicity can be identified, microphysiological systems (MPS) are being developed that better capture the complexity of in vivo physiology. We have previously described an organ-on-a-chip platform that incorporates perfused microvessels, such that survival of the surrounding tissue is entirely dependent on delivery of nutrients through the vessels. Here we describe an arrayed version of the platform that incorporates multiple vascularized micro-organs (VMOs) on a 96-well plate. Each VMO is independently-addressable and flow through the micro-organ is driven by hydrostatic pressure. The platform is easy to use, requires no external pumps or valves, and is highly reproducible. As a proof-of-concept we have created arrayed vascularized micro tumors (VMTs) and used these in a blinded screen to assay a small library of compounds, including FDA-approved anti-cancer drugs, and successfully identified both anti-angiogenic and anti-tumor drugs. This 3D platform is suitable for efficacy/toxicity screening against multiple tissues in a more physiological environment than previously possible.

Original languageEnglish (US)
Pages (from-to)511-520
Number of pages10
JournalLab on a Chip
Volume17
Issue number3
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Preclinical Drug Evaluations
Toxicity
Tumors
Screening
Tissue
Physiology
Hydrostatic pressure
Pharmaceutical Preparations
Nutrients
Tissue Survival
Monolayers
Assays
Neoplasms
Hydrostatic Pressure
Angiogenesis Inhibitors
Pumps
Microvessels
Food

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

Cite this

Phan, D. T. T., Wang, X., Craver, B. M., Sobrino, A., Zhao, D., Chen, J. C., ... Hughes, C. C. W. (2017). A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. Lab on a Chip, 17(3), 511-520. https://doi.org/10.1039/c6lc01422d

A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. / Phan, Duc T.T.; Wang, Xiaolin; Craver, Brianna M.; Sobrino, Agua; Zhao, Da; Chen, Jerry C.; Lee, Lilian Y.N.; George, Steven; Lee, Abraham P.; Hughes, Christopher C.W.

In: Lab on a Chip, Vol. 17, No. 3, 01.01.2017, p. 511-520.

Research output: Contribution to journalArticle

Phan, DTT, Wang, X, Craver, BM, Sobrino, A, Zhao, D, Chen, JC, Lee, LYN, George, S, Lee, AP & Hughes, CCW 2017, 'A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications', Lab on a Chip, vol. 17, no. 3, pp. 511-520. https://doi.org/10.1039/c6lc01422d
Phan, Duc T.T. ; Wang, Xiaolin ; Craver, Brianna M. ; Sobrino, Agua ; Zhao, Da ; Chen, Jerry C. ; Lee, Lilian Y.N. ; George, Steven ; Lee, Abraham P. ; Hughes, Christopher C.W. / A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. In: Lab on a Chip. 2017 ; Vol. 17, No. 3. pp. 511-520.
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