Pushing Analytical
Boundaries with
High‑Throughput LC/MS
Discover how two powerful platforms are
redefining workflows in high‑speed, high‑volume
science.
In cutting‑edge analytical labs, researchers sprint to unlock bio‑ Multiplexing to maximize LC/MS efficiency
marker secrets, ushering in a new era of tailored treatments. High‑throughput demands require labs to think beyond tradi‑
Simultaneously, toxicologists scrutinize pollution data, driving tional LC procedures, and Agilent’s StreamSelect system is
urgent solutions. The future belongs to those who innovate, designed for just that. StreamSelect boosts sample through‑
adapt and respond with lightning speed. put by multiplexing up to four LC streams into a single mass
High‑throughput liquid chromatography‑mass spectrometry spectrometer, all while maintaining chromatographic accuracy.
(LC/MS) tackles lab challenges with accuracy and agility, clear‑ The accompanying diagram illustrates how each of the four LC
ing data logjams long associated with LC analysis. This article streams injects samples at staggered intervals, reducing mass
explores how high‑throughput LC/MS can expand your lab's spectrometer idle time and enabling simultaneous analysis of
capabilities, covering key factors to consider when selecting multiple streams. This efficiency maximizes data collection,
the right system. Through real‑world examples from Agilent’s producing enhanced results within the same time window.
StreamSelect and RapidFire platforms, see how these tech‑ “With StreamSelect, you can easily quadruple the efficiency of
nologies optimize workflows across industries, from pharma‑ your mass spectrometer by staggering up to four injections
ceuticals to environmental monitoring. and focusing only on the key data segments,” says Kevin Mc‑
Cann, a Product Owner at Agilent. “It seamlessly adapts your
standard procedures to handle significantly more samples
while maintaining the same high standards of retention time,
separation quality, and analytical accuracy.”
System 1
0 min 4 min In a multiplexed system, having multiple LC streams provides
a built‑in safety net for handling errors. If one stream experi‑
System 2 ences a malfunction, the instrument can automatically shift to
1 min another operational path, ensuring that data collection contin‑
ues uninterrupted. This flexibility is critical for labs managing
System 3 large sample loads and maintaining consistent results—espe‑
2 min
cially during periods of high demand.
McCann highlights how StreamSelect’s ability to hold over
System 4
3 min 2,000 temperature‑controlled samples supports this uninter‑
rupted workflow, allowing for continuous operation during full
Collected shifts or even overnight. “When you return from an unattended
MS data run, you don’t want error messages—you want data ready for
analysis,” he advises.
The Agilent StreamSelect LC/MS system can collect four times the results
in the same time window by reducing MS idle time. One example of StreamSelect’s capabilities is in cardiovascular
research, where it measured the biomarkers ADMA and SDMA
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simultaneously. Using a four‑stream multiplexed LC/MS setup, RapidFire’s automation supports thousands of samples with
each stream fed into a single mass spectrometer, signifi‑ minimal oversight, adapting to different plate formats—from
cantly increasing sample throughput. This method maintained 96‑well to 1536‑well microplates. Integrated robotics, plate
accuracy across runs, with precise retention times, strong storage, and a barcode reader facilitate sample handling. With
reproducibility, and high sensitivity. ADMA and SDMA showed temperature‑controlled storage and reusable SPE cartridges,
linear results over a broad concentration range, with clear and RapidFire delivers consistent results over extended runs. For
well‑separated peaks. even greater efficiency, its 'BLAZE' mode allows direct flow‑
StreamSelect demonstrates exceptional reliability over ex‑ injection, reducing acquisition times to as little as 2 seconds
tended workloads, as shown in a study of 1,000 continuous per sample.
injections of six cannabinoids. Retention time reproducibility A recent case study highlights RapidFire’s impact in drug dis‑
across the four streams achieved relative standard deviations covery, where it’s accelerating macromolecular analysis with
as low as 1.54%. native mass spectrometry. Brandon Ruotolo of the University
of Michigan describes how RapidFire has transformed their
Using SPE to supercharge LC/MS speed workflow, reducing analysis times from hours to about 30 sec‑
McCann notes that StreamSelect provides a straightforward onds per sample. This rapid processing enables high‑through‑
upgrade when moving from traditional LC/MS to high‑through‑ put screening, delivering detailed data on binding stoichiom‑
put solutions. Labs can use the same methods, data formats, etry, protein stability, and interaction dynamics—critical factors
and retention times as their current LC/MS setup, without in drug discovery that go beyond simple yes/no binding results.
needing to adjust workflows or mass spec data. Designed with both efficiency and space in mind, RapidFire
But when speed is paramount, RapidFire offers a clear ad‑ combines its ultra‑fast sampling capabilities with compact
vantage. By bypassing conventional LC separation and using instrumentation. Its compatibility with Agilent’s Ultivo triple
automated, micro‑scale solid‑phase extraction (SPE) cartridg‑ quadrupole MS further enhances sensitivity while conserving
es, it prepares samples and acquires data in as little as 8–15 bench space. For labs with limited room, this makes RapidFire
seconds. Samples are aspirated from well plates, loaded onto an ideal fit.
an SPE cartridge, washed to remove salts and buffers, and
optionally rinsed to clear weakly bonded molecules. An elution Expanding applications of high-throughput LC/MS
solvent then directs the analytes to the mass spectrometer, High‑throughput LC/MS is advancing possibilities across both
while the cartridge quickly re‑equilibrates for the next sample, established and cutting‑edge fields. From regulatory testing to
ensuring high‑throughput alongside accuracy. synthetic biology, advanced instrumentation enables labs to
achieve faster, more adaptable workflows while maintaining
rigorous data quality.
Load/wash Extra wash Elute Re-equilibrate
Maximize throughput for rapid screening
Binding solvent Wash solvent To MS Binding solvent
The speed and efficiency of high‑throughput instrumentation
make it ideal for high‑volume, rapid screening applications.
In fields such as food safety and forensic science, RapidFire
has accelerated critical analyses including antibiotic residue
screening in honey and smokeless powder detection in soil,
reducing sample processing times to just seconds. Stream‑
RapidFire RapidFire RapidFire RapidFire Select has also proven its value in high‑throughput screening
Cartridge Cartridge Cartridge Cartridge
by quadrupling sample analysis for complex testing, such as
cannabinoid quantitation in urine.
To waste To waste Elution solvent To waste
Analytes of interest Adapt and scale existing methods
Molecules similar to analytes of interest
Salts For labs seeking to scale up without reworking existing meth‑
Buffers ods, StreamSelect provides a direct path to higher throughput.
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This adaptability makes it a strong choice for clinical research izing LC and MS data in a robust system compatible with exist‑
and environmental labs. ing LC/MS formats.
Enhance analytical accuracy
Navigating high-throughput options
Both platforms contribute to increased analytical accuracy,
Ultimately, the right high‑throughput LC/MS system depends on
especially in complex sample matrices. RapidFire has shown
your lab’s requirements. StreamSelect is ideal for chromatog‑
robust performance in applications such as opioid profiling,
raphy‑based workflows, offering multiplexing with full integrity,
where precise quantitation is essential. StreamSelect also
while RapidFire bypasses these steps for unmatched speed.
ensures consistent accuracy in these types of analyses, main‑
taining retention time reproducibility and low relative standard “It’s not always about choosing between StreamSelect and Rapid‑
deviation across hundreds of injections. Fire; many labs benefit from using both,” McCann explains. “The
decision hinges on the unique demands of each application.”
Automate workflows
Ready to push the limits of what’s possible? Use the decision
Automation powers high‑throughput LC/MS, and RapidFire’s
tree to discover strategic pathways, and connect with your
solid‑phase extraction (SPE) technology is a strong fit for
Agilent representative to see how these solutions can expand
applications in synthetic biology. For microbial cell factories
your lab’s potential.
converting renewable feedstocks into valuable chemicals and
materials, RapidFire offers an efficient and precise approach
to strain screening. Both RapidFire and StreamSelect integrate
advanced data management and analysis software, central‑
RapidFire StreamSelect
– Processes samples in as little as 2 seconds. – Increases throughput up to 4x while preserving
– Achieves high‑throughput without compromising data chromatographic separation.
integrity. – Analyzes up to 1,000 samples daily with staggered LC
– Automates data acquisition of up to 130,000 samples. injections.
– Integrated robotics enable hands‑free operation. – Integrates easily into workflows, streamlining the transition to
high‑throughput.
– Reusable SPE cartridges minimize solvent use and waste.
– Operates continuously with automatic error handling to
prevent sample loss.
– Scales effortlessly, ideal for handling demand surges.
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High‑throughput LC/MS:
How Will You Push the Boundaries?
Maximize Throughput for Rapid Screening Automate Workflows
Biopharma: Food: R&D: Clinical Research: Environmental: Food:
Lead the market Verify authenticity Condense Automate Be the authority Guarantee trust
by slashing with unmatched years of biomarker in real‑time with seamless,
discovery speed. discovery into analysis for 24/7 pollutant tracking. continuous
timelines. mere months. research. monitoring.
Can you use SPE for Is your priority full
SPE purification, or is LC LC Speed automation with speed, or Detail
separation a must? chromatographic detail?
RapidFire StreamSelect
Do you need to maintain
NO YES
exact LC conditions?
Adapt and Scale Existing Methods Enhance Analytical Accuracy
Pharma: Bioanalysis: Environmental: Pharma: Forensics: Profiling:
Improve Expand testing Manage demand Set the standard Ensure evidence Shape the future
PK studies with capabilities with surges without for drug purity integrity with of molecular
faster processing. proven assays. changing and compliance. precise analysis. analysis.
workflows.
The right choice isn’t always obvious—many labs use
both solutions. Contact an Agilent representative to find
the best fit for your high-throughput needs.
www.agilent.com/en/contact-us/page 4
