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Hardware Capability (Clink for throughput
capability and target applications in ChemCORE)
GENERAL DESCRIPTION
ChemCORE houses several liquid handlers including
one Tekbench™ Work Station, two Cybi-Well™ systems,
and BioMek2000™ work station. They are capable
of handling 96- and 384-well plates in a variety
of formats including high throughput liquid handling,
cherry-picking and volume dispensing. The detection
modules include the
BD Pathway™ 855
Bioimager, Epic ™ System,
Tecan Safire 2 reader,
Aquest™
(currently Analyst GT) plate
reader,
ICR-8000™ atomic
absorption spectrometer, SpectraMax™ 340 reader,
and LAS-3000 Fuji imaging station. The liquid handling
and detection module are highly integrated by a
Mitsubishi RV-2AJ robotic arm and Zymark Twister™ II
arm. In addition, both liquid handling modules and
detection modules are robotically linked to accessory
units including a Kendro Cytomat 6070 automated
incubator, Elx-405 plate washers, and Multidrop
dispensers.
The integration and performance of liquid
handlers, detection modules and accessory
equipment are controlled by customized a Genera™ software
package, which allows for multi-tasking of
instrument clusters, web-based remote monitor/control,
as well as stand-alone performance of individual
units. The data acquisition, analyses, and
storage are carried out by several CPUs and
managed by an Oracle server along with several
software packages to perform SAR and chemoinformatics
analyses. Data access and analyses can be
performed within our ChemCORE-maintained network.
DETECTION INSTRUMENTS
FDSS6000 System,
a high-throughput kinetic
fluorescence reader by
Hamamatsu
http://www.fdssdrug.com
Brief
description (
for throughput details )
The FDSS6000 System is an
imaging based plate reader for
cellular assays, assay
development and high
throughput screening which can
utilize both fluorescence and
luminescence modalities.
FDSS 6000 can
respond to various fluorescent
probes, and can perform
cell-based assay at high speed
and with high precision. Since
it corresponded to High
Throughput Screening (HTS),
the multi-dispenser and the
micro plate automatic handling
system were equipped, and
improvement in the speed and
automation were realized. The
fluorescence observation
application of ion imaging and
FRET can be supported, and the
dispenser of a maximum of 3
sets can be loaded.
Simultaneous loading of the
object for fluorescence and
the camera for luminescence is
possible.
Uses and
applications
1.
Netzer, R.,
Bischoff, U. & Ebneth, A. HTS
techniques to investigate the
potential effects of compounds
on cardiac ion channels at
early-stages of drug
discovery. Current Opinion
in Drug Discovery &
Development 6, 462
- 469 (2003).
2. Kim, H. S. et al. Design,
synthesis, and biological
evaluation of
1,3-dioxoisoindoline-5-carboxamide
derivatives as T-type calcium
channel blockers.
Bioorganic & Medicinal
Chemistry Letters 17,
476-481 (2007).
3. Poul, E. L. et al.
Adaptation of Aequorin
Functional Assay to High
Throughput Screening. J
Biomol Screen 7,
57-65 (2002).
Epic ™ System,
a high-throughput label-free
detection platform from
Corning®
http://www.corning.com
Brief
description (
for throughput details )
The Epic™
System is a new
high-throughput label-free
detection platform from
Corning, Inc, consisted of an
SBS-standard 384-well
microplate with optical
sensors and HTS-compatible
microplate reader capable of
reading up to 40,000 wells per
8 hours and a set of
label-free, direct-bind and
functional assay protocols.
Its sensitivity of 5pg/mm2
enables the detection of the
binding of a 300Da compound to
a 70kDa immobilized target
with CVs of 10% or less. This
powerful combination of
features and performance
capabilities not only enables
researchers to evaluate many
of the biomolecular
interactions in molecular and
cellular biology, but also
provides the added benefit of
integration with an already
installed HTS capital base. In
addition, the Epic™ System
makes the screening of
"intractable" targets and
pathway interactions that
cannot be screened today
possible. The universal
applicability of the Epic™
System across biochemical
assay types also enables the
discovery of new chemical
entities (small molecule) as
well as new biological
entities (large molecule).
Uses and
applications
1. Wu, Meng;
Coblitz, Brian; Shikano,
Sojin; Long, Shunyou; Spieker,
Matt; Frutos, Anthony G.;
Mukhopadhyay, Sunil; Li, Min,
Phospho-specific recognition
by 14-3-3 proteins and
antibodies monitored by a high
throughput label-free optical
biosensor. FEBS Letters, In
Press.
2. Fang, Ye;
Ferrie, Ann M.; Fontaine,
Norman H.; Mauro, John;
Balakrishnan, Jitendra,
Resonant Waveguide Grating
Biosensor for Living Cell
Sensing. Biophys. J. 2006, 91,
(5), 1925-1940.
3. Fang, Ye;
Ferrie, Ann M.; Li, Guangshan,
Cellular functions of
cholesterol probed with
optical biosensors. Biochimica
et Biophysica Acta (BBA) -
Molecular Cell Research 2006,
1763, (2), 254-261.
Ion Channel
Reader 8000 and 12000,
an atomic absorption
spectroscopy and flux assay
based ion channel activity
detection system from Aurora
Biomed Inc.
http://www.aurorabiomed.com
Brief
description (
for throughput details )
The ICR 8000
detects ion channel activity
using atomic absorption
spectroscopy and flux assays. Fux assays utilize tracer ions
to study the ion channel of
interest. The Ion Channel
Reader 8000 provides a medium
throughput format up to 5000
data points/day for ion
channel screening by the flux
assay approach. The ICR 8000
displays broad utility; it can
be applied to assess
voltage-gated (hERG, BK/SK,
Kv1.1, 1.4, 1.5, KCNQ, 2P,
etc.) and ligand-gated (KATP,
nAChR, etc.) potassium
channels, voltage-gated sodium
channels (SCN5a, Nav1.2) and
transporters (Na/K-ATPase, K-Cl
Co-transporter). This allows
researchers to accelerate drug
development efforts in the
treatment and prevention of
diseases associated with ion
channels. It can accommodate
both 96 and 384 well plates
with CV less than 5%.
The ICR 12000
system is essentially
identical to ICR8000.
the primary difference lies
that it is a 12 burners
instead of a single burner in
ICR8000. Hence, ICR12000
increases the throughput by a
factor of 12.
Uses and
applications
1. Terstappen,
Georg C., Functional Analysis
of Native and Recombinant Ion
Channels Using a High-Capacity
Nonradioactive Rubidium Efflux
Assay. Analytical Biochemistry
1999, 272, (2), 149-155.
2. Tang, Weimin;
Kang, Jiesheng; Wu, Xiaying;
Rampe, David; Wang, Lin; Shen,
Hong; Li, Zhuyin; Dunnington,
Damien; Garyantes, Tina,
Development and Evaluation of
High Throughput Functional
Assay Methods for hERG
Potassium Channel. J Biomol
Screen 2001, 6, (5), 325-331.
3. Terstappen,
Georg C., Nonradioactive
Rubidium Ion Efflux Assay and
Its Applications in Drug
Discovery and Development.
ASSAY and Drug Development
Technologies 2004, 2, (5),
553-559.
4. Sun H,
Shikano S, Xiong Q & Li M
(2004).
Function
recovery after chemobleaching
(FRAC): evidence for activity
silent membrane receptors on
cell surface.
Proc Natl Acad Sci USA
101(48):16964-9.
5. Sun, Haiyan;
Liu, Xiaodong; Xiong, Qiaojie;
Shikano, Sojin; Li, Min,
Chronic Inhibition of Cardiac
Kir2.1 and hERG Potassium
Channels by Celastrol with
Dual Effects on Both Ion
Conductivity and Protein
Trafficking. J. Biol. Chem.
2006, 281, (9), 5877-5884.
BD Pathway™
855 Bioimager,
an automated, confocal,
real-time, single cell kinetic
and endpoint imaging system from
BD Biosciences.
http://www.bdbiosciences.com
Brief
description (
for throughput details )
The BD Pathway
Bioimager is an automated,
confocal, real-time, single
cell kinetic and endpoint
imaging system that has been
integrated into a single,
compact unit. The BD Pathway
was designed to provide
high-resolution, automated
confocal imaging with
sophisticated imaging software
to assist in developing better
cell-based assays. The system
allows the user to explore
biological events without many
of the restrictions of
conventional microscope-based
high content imaging systems.
BD Pathway
offers:
§
True confocal
real-time imaging
§
Full-spectrum
laser-free illumination
§
Ability to run
kinetic and endpoint assay
formats
§
Integrated
liquid handling with
image-as-you-add capability
§
96- and
384-multiwell plate and slide
imaging
§
Environmentally
controlled for live cell
experiments
§
Flexible
software allowing easy data
navigation and classification
§
Integrated
binocular viewing
§
Ultra-high
precision linear x,y, and z
motors
Uses and
applications
1. Chan, Grace
K. Y.; Richards, Gillian R.;
Peters, Marco; Simpson, Peter
B., High Content Kinetic
Assays of Neuronal Signaling
Implemented on BDTM Pathway
HT. ASSAY and Drug Development
Technologies 2005, 3, (6),
623-636.
2. Lang, Paul;
Yeow, Karen; Nichols, Anthony;
Scheer, Alexander, Cellular
imaging in drug discovery. Nat
Rev Drug Discov 2006, 5, (4),
343-356.
3. Timothy, J.
Mitchison, Small-Molecule
Screening and Profiling by
Using Automated Microscopy.
ChemBioChem 2005, 6, (1),
33-39
Safire²™ plate
reader,
a monochrometer based
multifuntional plate reader from
Tecan.
http://www.tecan.com
Brief
description (
for throughput details )
Safire² has
been developed with the drug
discovery process in mind. Due
to its in-built flexibility,
sensitivity and performance,
Safire² is the ideal
instrument to bridge the gap
between assay development and
high throughput screening.
Safire² is a fully modular
monochromator-based microplate
detection system that offers a
range of high speed detection
techniques. In assay
development, which requires
frequent changing of
applications and fluorophores,
the monochromator-based
Safire² eliminates the need
for cumbersome filter changes
thereby saving time and money.
The modular concept
of Safire² allows upgrades to
new detection modes at any
time if there is a need to
have access to further
applications. Detection
modules are available for top
and bottom fluorescence
intensity measurements,
fluorescence polarization
studies and multi-channel
absorbance and luminescence
measurements. Safire² is
easily combined with a stacker
module for batch processing of
up to 50 microplates.
Uses and
applications
1. Park SH,
Raines RT. Fluorescence
polarization assay to quantify
protein-protein interactions.
Methods Mol Biol.
2004;261:161-6.
2. Lakowicz, J.R. Principles
of Fluorescence Spectroscopy,
2nd ed., Plenum, New York,
1999.
3. Valeur, B.
Molecular Fluorescence, Wiley-VCH,
Weinheim, 2001.
4. Wu, Meng;
Coblitz, Brian; Shikano,
Sojin; Long, Shunyou;
Cockrell, Lisa M.; Fu, Haian;
Li, Min, SWTY-A general
peptide probe for homogeneous
solution binding assay of
14-3-3 proteins. Analytical
Biochemistry 2006, 349, (2),
186-196.
5. Coblitz,
Brian; Shikano, Sojin; Wu,
Meng; Gabelli, Sandra B.;
Cockrell, Lisa M.; Spieker,
Matt; Hanyu, Yoshiro; Fu,
Haian; Amzel, L. Mario; Li,
Min, C-terminal Recognition by
14-3-3 Proteins for Surface
Expression of Membrane
Receptors. J. Biol. Chem.
2005, 280, (43), 36263-36272.
Aquest™
(currently Analyst GT) plate
reader,
a filter based multifunction
plate reader  from
LJL system (currently
Molecular Devices).
http://www.moleculardevices.com
Brief
description
(
for throughput details )
Analyst set the
standard for no-compromise
performance in 384-well plates
when it was introduced.
Acquest, the first
commercially available 1536
multimode reader, brought that
performance to high-density
microplates. Now Analyst GT
builds on that reputation with
significantly faster read
speeds for all plate formats.
Analyst GT achieves this
performance with
second-generation SmartOptics™,
a unique system that selects
and configures light sources,
filters, detectors, and
optical paths to ensure
maximum assay performance.
Previously, systems that
offered 96- through 1536-well
compatibility sacrificed read
time or sensitivity to read
high-density 1536-well plates.
Analyst GT improves on Acquest,
the benchmark for 1536-well
point reading systems, by
dramatically increasing read
speed without compromising
signal-to-noise and
signal-to-background.
Uses and
applications
1. Park SH, Raines RT.
Fluorescence polarization
assay to quantify
protein-protein interactions.
Methods Mol Biol.
2004;261:161-6.
2. Lakowicz, J.R. Principles
of Fluorescence Spectroscopy,
2nd ed., Plenum, New York,
1999.
3. Valeur, B.
Molecular Fluorescence, Wiley-VCH,
Weinheim, 2001
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