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Issue 4 Summer 2002 - Applied Biosystems

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4<br />

O<br />

Corporate review<br />

Introducing the Next Generation of Production<br />

Level DNA Analysis Systems<br />

n April 23, <strong>2002</strong> <strong>Applied</strong> <strong>Biosystems</strong> announced<br />

the introduction of the <strong>Applied</strong> <strong>Biosystems</strong> 3730<br />

and 3730xl DNA Analyzers. These next generation<br />

production scale systems are expected to improve<br />

data quality and increase productivity by a factor<br />

of two or more compared to current technology<br />

platforms. They bring powerful new tools for rapid,<br />

accurate, and cost-effective DNA analysis to<br />

discovery researchers worldwide studying human<br />

and other genomes.<br />

The addition of the 3730 and 3730xl DNA Analyzers<br />

to the <strong>Applied</strong> <strong>Biosystems</strong> existing portfolio of<br />

industry-leading DNA analyzers provides researchers<br />

with a wider range of platforms to address their<br />

throughput and application needs. The 3730<br />

analyzer, a 48-capillary electrophoresis system,<br />

combines the core technology of the highly successful<br />

ABI PRISM ® 3100 Genetic Analyzer with new advances<br />

in automation and optics, to meet the needs of higher<br />

throughput individual researchers and core facilities.<br />

The 3730 platform can also be upgraded to the<br />

3730xl DNA Analyzer, the 96-capillary successor to<br />

the ABI PRISM ® 3700 DNA Analyzer.<br />

While researchers and production facilities are<br />

expected to primarily use the 3730xl DNA Analyzer<br />

for production sequencing – both de novo and<br />

resequencing – the 3730 DNA Analyzer is expected<br />

to be used for a wider range of sequencing and<br />

fragment analysis applications including de novo and<br />

comparative sequencing and genotyping. The new<br />

systems run both ABI PRISM ® BigDye ® Terminator<br />

chemistries for sequencing and five-dye chemistries<br />

for fragment analysis, as do all <strong>Applied</strong> <strong>Biosystems</strong><br />

DNA analyzers.<br />

Throughput, Automation, Efficiency Improvements<br />

The 3730 and 3730xl DNA Analyzers can<br />

reduce sequencing project costs and increase<br />

efficiency by providing longer read lengths,<br />

enhanced instrument sensitivity and efficiency<br />

and the highest 24-hour unattended capacity of any<br />

DNA analyzer. Sequence read lengths of greater<br />

than 1,000 base pairs and improved basecalling<br />

could reduce the number of samples needed<br />

to complete de novo genome sequencing and<br />

resequencing projects by 20-40% respectively.<br />

<strong>Applied</strong> <strong>Biosystems</strong>: Pioneers in Genetic Analysis Systems<br />

Both new systems are part of the pioneering line of<br />

capillary electrophoresis instruments for DNA<br />

analysis from <strong>Applied</strong> <strong>Biosystems</strong>. The ABI PRISM ®<br />

310 Genetic Analyzer, the first commercially<br />

available capillary sequencer, was introduced in<br />

1995. That was followed in 1998 by the introduction<br />

of the 96-capillary ABI PRISM ® 3700 DNA Analyzer.<br />

Government and commercial researchers in the<br />

United States, Europe and Asia used the 3700<br />

system to sequence the human genome.<br />

Researchers worldwide currently use the 3700<br />

system for the industrial-scale analysis of genomic<br />

information. The 16-capillary ABI PRISM ® 3100<br />

Genetic Analyzer, introduced in 2000 was designed<br />

to provide the flexibility of the 310 system with<br />

added throughput for medium-to-high throughput<br />

laboratories. The ABI PRISM ® 3100-Avant Genetic<br />

Analyzer, introduced in April <strong>2002</strong>, is a four-capillary<br />

electrophoresis system that can be upgraded to the<br />

16-capillary 3100 system (see page 14).<br />

Applera Announces New Knowledge Business for<br />

Celera Discovery System (CDS)<br />

Applera Corporation announced earlier this year that<br />

its <strong>Applied</strong> <strong>Biosystems</strong> Group will become the<br />

exclusive distributor of the Celera Discovery System <br />

(CDS) operated by its Celera Genomics Group and<br />

that <strong>Applied</strong> <strong>Biosystems</strong> will integrate CDS and other<br />

genomic and biological information into a new<br />

Knowledge Business.<br />

For the future, <strong>Applied</strong> <strong>Biosystems</strong> has plans for<br />

its Knowledge Business to include genomic assays<br />

and related content (see page 29), as well as other<br />

information-rich products, services, and analytical<br />

tools to meet the needs of its life sciences<br />

customers. The Knowledge Business products and<br />

services will be marketed, in part, on an expanded<br />

information portal.<br />

For more information on<br />

3730/3730xl DNA Analyzers enter: No. 401<br />

Q TRAP LC/MS/MS System<br />

More Metabolites, More Proteins, More Confidence in Your Results<br />

Prof. Gérard Hopfgartner, University of Geneva, Switzerland<br />

O<br />

ne of the first steps in the investigation of the<br />

biotransformation of a new potential drug is the<br />

characterisation of its metabolites in in vitro systems.<br />

To cope with new demands of the pharmaceutical industry,<br />

such as reducing the discovery and development time of new<br />

drugs, powerful tools are needed to complete the various tasks.<br />

This is particularly true for the bioanalytical support for<br />

drug metabolism and pharmacokinetics studies. Many in vitro<br />

samples can be generated using hepatocytes and microsomes<br />

from different species and liquid chromatography combined<br />

with mass spectrometry (LC/MS) already plays a very important<br />

role in this field. Once these metabolites have been<br />

characterised in vitro it is important to monitor their presence<br />

in vivo and to follow their pharmacokinetic profile. The goal is<br />

to obtain as much information as possible regarding the<br />

structure of the metabolites present in plasma and their<br />

quantity in a very short period of time. Often in vivo samples<br />

contain very low concentrations of the drug and its metabolites<br />

and only limited sample volume is available. Sensitivity in the<br />

cover story<br />

low nanogram range is required and the challenge can be<br />

compared to the search for ‘needles in a haystack’<br />

Currently there is no unique mass spectrometer which has<br />

all the desired features required for this type of work and<br />

most laboratories use the combination of various types of<br />

mass spectrometers (MS) including triple quadrupole, ion trap,<br />

quadrupole time-of-flight (QqTOF) MS with relative long<br />

analysis times. Good chromatographic separation remains an<br />

important element. Selective scan modes such as neutral<br />

loss scan and precursor scan experiments which can be<br />

performed on triple quadrupole instruments, are very important<br />

to determine the biotransformation products in complex<br />

matrices. Phase I metabolites such as oxidative products or<br />

phase II metabolites (glucuronides or sulphates) can be rapidly<br />

identified using this technology.<br />

On triple quadrupole instruments the sensitivity in product ion<br />

scan mode is often not sufficient to obtain good spectra quality.<br />

QqTOF technology can overcome this lack of sensitivity with<br />

additional accurate mass information.<br />

page 6<br />

5

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