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omation mbers - Society for Laboratory Automation and Screening

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8:00 am Wednesday, February 4 Emerging Technologies – Cell Based <strong>Screening</strong> Room A3<br />

Evan Cromwell<br />

Blueshift Biotechnologies, Inc.<br />

238 E. Caribbean Drive<br />

Sunnyvale, Cali<strong>for</strong>nia 94089<br />

ecromwell@blueshiftbiotech.com<br />

Novel Cellular Analysis Plat<strong>for</strong>m <strong>for</strong> Drug Discovery<br />

124<br />

Co-Author(s)<br />

Chris Shumate,<br />

Paul B. Comita<br />

The drug discovery industry is in need of improved screening technologies that provide knowledge <strong>and</strong> <strong>for</strong>esight<br />

into success of new drug c<strong>and</strong>idates. Currently most discovery ef<strong>for</strong>ts make use of fluorescence intensity <strong>for</strong> high<br />

throughput <strong>and</strong> high content screening (HTS/HCS). One of the more recent developments in optical imaging <strong>for</strong><br />

complex biological systems is the use of fluorescence emission lifetime <strong>for</strong> imaging microscopy (FLIM). Fluorescent<br />

lifetime <strong>and</strong> polarization imaging of cells provide powerful tools <strong>for</strong> assays that use detection of the presence,<br />

quantity, <strong>and</strong> location of labeled molecules <strong>and</strong> their binding state. Incorporating these features into a fast <strong>and</strong><br />

inexpensive commercial product is a significant technical challenge. Blueshift Biotechnologies is addressing<br />

this challenge by exploiting recent advances in laser sources, semiconductor inspection technology, fluorescent<br />

probes, <strong>and</strong> high content screening. Blueshift will present a novel cellular analysis plat<strong>for</strong>m to drive drug discovery<br />

research <strong>and</strong> HTS applications.<br />

8:15 am Wednesday, February 4 Emerging Technologies – Cell Based <strong>Screening</strong> Room A3<br />

James Costantin<br />

Molecular Devices Corp.<br />

1131 Orleans Drive<br />

Sunnyvale, Cali<strong>for</strong>nia 94089<br />

<strong>Screening</strong> <strong>for</strong> Ion Channel Modulators Using the IonWorks HT System<br />

Co-Author(s)<br />

Shawn H<strong>and</strong>ran, Andrew Wittel,<br />

Sven Brown, Nick Callamaras,<br />

Wilhelm Lachnit<br />

The IonWorks HT instrument is an automated high throughput voltage clamp plat<strong>for</strong>m that measures whole-cell<br />

currents from multiple cells in parallel using 384-well PatchPlates. This robust, turn-key plat<strong>for</strong>m per<strong>for</strong>ms highly<br />

consistent, single-point lead c<strong>and</strong>idate screens <strong>for</strong> modulators of ion channel activity <strong>and</strong> has the fidelity required<br />

<strong>for</strong> IC50 determinations. Successful recordings have been obtained from a variety of cultured cell lines (e.g., CHO,<br />

CHL, HEK) expressing recombinant ion channels. For single-point screening, data was generated from compound<br />

plates prepared containing r<strong>and</strong>omly distributed compounds as well as controls. Following the identification of<br />

active wells, an 8-point IC50 curve <strong>for</strong> each compound was obtained. Results are presented <strong>for</strong> compounds that<br />

affect hERG, Na+ <strong>and</strong> other voltage-gated ion channels. The IC50 curves generated from IonWorks HT are<br />

comparable to values obtained in parallel by conventional patch clamp electrophysiology. IonWorks HT provides<br />

an enormous opportunity to screen pharmaceutical compound libraries directly at the electrophysiological level <strong>for</strong><br />

more cost-effective <strong>and</strong> accelerated identification of therapeutic ion channel targets.

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