High throughput optical sensor arrays for drug screening

In the world of drug discovery, high throughput whole cell assays are a critical step in discovering therapeutically relevant drug compounds [1]. This report details the development of several novel sensor systems capable of detecting cellular ion flux in multi-well plate format. Optodes are employed as the primary sensors, which are an optically based ion selective polymer. These assays utilize both potassium and sodium selective optodes to provide real time measurements of extracellular ion concentration, which can yield extremely valuable information regarding compound induced cellular activity [2]. Individual assay formats have been specifically tailored for use with both adherent and suspended cell lines. For adherent cell lines, the optode based sensor system was evaluated using an HEK 293 cell model. To evoke cellular activity, the cells were exposed to Isoproterenol and Forskolin, which are known to elicit intracellular cyclic AMP production. The assay proved robust in detecting long term drug induced extracellular potassium flux. Ion flux magnitude was used to generate EC50 values of 1.185 nM and 66.5 nM for Isoproterenol and Forskolin, respectively. These values correlate closely with reported values that were attained with assays using intracellular calcium as the active biomarker [3-5].

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Mechanical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Harjes, Daniel I

Advisor dc:contributor.advisor

• Heather A. Clark and Roger D. Kamm.

• Mechanical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/38270

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38270