Nanoliter Cell Culture Array with Tunable Chemical Gradients

Jonathan Avesar, Yaron Blinder, Hadar Aktin, Ariel Szklanny, Dekel Rosenfeld, Yonatan Savir, Moran Bercovici, Shulamit Levenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

A multitude of cell screening assays for diagnostic and research applications rely on quantitative measurements of a sample in the presence of different reagent concentrations. Standard methods rely on microtiter plates of varying well density, which provide simple and standardized sample addressability. However, testing hundreds of chemical dilutions requires complex automation, and typical well volumes of microtiter plates are incompatible with the analysis of a small number of cells. Here, we present a microfluidic device for creating a high-resolution chemical gradient spanning 200 nanoliter wells. Using air-based shearing, we show that the individual wells can be compartmentalized without altering the concentration gradient, resulting in a large set of isolated nanoliter cell culture wells. We provide an analytical and numerical model for predicting the concentration within each culture chamber and validate it against experimental results. We apply our system for the investigation of yeast cell metabolic gene regulation in the presence of different ratios of galactose/glucose concentrations and successfully resolve the nutrient threshold at which the cells activate the galactose pathway.

Original languageEnglish
Pages (from-to)7480-7488
Number of pages9
JournalAnalytical Chemistry
Volume90
Issue number12
DOIs
StatePublished - 19 Jun 2018
Externally publishedYes

Funding

FundersFunder number
Israel Innovation Authority in Israel’s Ministry of Economy
Israel Science Foundation1902/12
Planning and Budgeting Committee of the Council for Higher Education of Israel

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