integrated LC 

Built for Reliability: Experience exceptional robustness and consistently accurate analytical results you can trust.

Sustainable by Design: Crafted from sustainable materials and featuring new functions to reduce your environmental impact.

Uncompromising Performance: Delivers the same outstanding capabilities as previous models in an eco-friendlier design.

As the global demand for both efficiency and sustainability transforms analytical operations, Shimadzu’s innovative “smart” and “eco-friendly” solutions help users reduce their environmental impact while boosting productivity.

Green Transformation

Eco-Friendly Solutions for People and the Planet

Sustainable Material Integration
Chemically recycled plastics are used in select product components to decrease reliance on petroleum and limit carbon dioxide output.

Optimized Packaging Materials
Smarter packaging design—lighter, smaller, and more efficient—helps cut shipping costs and reduce environmental impact.

Lower Running Costs
Higher durability of parts reduces replacement frequency. That means fewer analysis interruptions during part replacements, which increases the instrument uptime rate and improves operating efficiency.

Lower Power Consumption
The auto-shutdown function minimizes power consumption while in the standby mode after analyses, which can reduce standby mode power consumption by 95 % or more compared to the regular standby mode.

intelligent

The new i-Series models offer three key functionalities for diagnosis, prevention, and system restoration to maintain analytical robustness.

Diagnoses Pump and Autosampler Status

During the pump’s flow path check, the system identifies check valve malfunctions, while the autosampler’s flow path check detects contamination and blockages in the injection system.

Automatic Equilibration with Column Protection

To prevent column deterioration caused by sudden pressure spikes, the mobile phase flow rate should be gradually increased as the column temperature rises. The FlowPilot flow rate control feature is synchronized with the column oven temperature, ensuring columns are protected from abrupt pressure changes during automatic equilibration.

iCMP Next-Generation Column Management

Maintaining a record of column usage history is crucial for ensuring high data reliability. The intelligent Column Management Platform (iCMP)* provides an integrated solution for tracking column usage,
improving both usability and data integrity.

* Sold separately. Only available with LabSolutions CS.

iCMP Next-Generation Column Management

innovative

Enhancing Workflows Through Automation and Remote Monitoring

With FlowPilot automated flow rate control, mobile phase monitoring, Analytical Intelligence driven functionality, and LabSolutions Direct software, everything from system startup to analysis shutdown can be managed through automated processes or remote control/monitoring. These automated workflows embed the expertise of seasoned analysts, ensuring consistent data acquisition over extended periods while reducing manual labor in the lab and enhancing overall productivity.

intuitive

The intuitive user interface mirrors the system’s flow path, allowing users to easily visualize operating status. Methods can be created or edited directly from the same screen, streamlining operation. Designed for ease of use, the interface enables even first-time liquid chromatography users to get started with minimal training.

The auto-validation function allows any user to follow a standardized procedure to easily verify instrument condition. It automatically checks key performance metrics, such as solvent delivery stability, wavelength and absorbance accuracy, gradient precision, and signal drift or noise. In addition, a built-in instrument check function performs routine pre-run inspections and generates a comprehensive report with self-diagnostic results and consumables usage—tracking solvent volume delivered, total injections by the autosampler, and lamp operating hours. All auto-validation results are centrally managed, enabling quick and accurate assessment of instrument status.

Limit sales to areas where utilities can be procured and systems can be supported.

Biomass energy, chemical recycling, and other new technologies are being researched and developed around the world in an effort to achieve a carbon-neutral society. However, there is concern that, unlike conventional fossil fuels, new raw materials generated from such R&D efforts may contain hydrocarbon mixtures that could have a detrimental effect on product quality or production processes. Of the hydrocarbons involved, it can be particularly difficult to detect heterocyclic compounds selectively with high sensitivity. Shimadzu’s unique ELEM-SPOT system is the world’s first Gas Chromatograph Mass Spectrometer (GC-MS) with an element-selective combustion unit (EL-30) included for selectively analyzing nitrogen-containing compounds or oxygenated compounds in complex hydrocarbon compounds with high sensitivity.

Principle of Detecting Oxygenated Compounds

• If now-common CxHyNzOw hydrocarbons are directly detected by FID or GC-MS after column separation, then they are detected based on a single peak. If that peak is detected by GC-MS after column separation and oxidative dissociation, and further analyzed by m/z, then MS chromatograms are obtained for each product of oxidative dissociation. Since the dissociation products are unique for each element contained in the compound, a unique chromatogram is obtained for each specific hetero-element contained in the compound.

In the analysis of oxygenated compounds, oxidative decomposition is performed using isotopic oxygen (¹⁸O₂) in the carrier gas, and screening is conducted to separate oxygen-containing compounds from other components.
Dedicated data analysis tools are employed to accurately identify oxygen-containing compounds.

• ¹⁸O₂ (Isotopic) Oxidation Gas
• ¹⁶O₂ Oxidation Gas

ELEM-SPOT, UFMS, LabSolutions and ClickTek are trademarks of Shimadzu Corporation or its affliated companies in Japan and/or other countries.

Spotting Targets Selectively

Hydrocarbon compounds are first separated by GC and then oxidatively dissociated in the element-selective combustion unit. Then the separated compounds are detected by MS using the selected ion monitoring (SIM) mode. As a result, the difficult analysis of trace quantities of an oxygenated compound was enabled by using isotopic oxygen (¹⁸O₂) as the oxidation gas (Pat. No. WO 2017/114654). Furthermore, nitrogen-containing compounds can be detected selectively by using regular oxygen (¹⁶O₂) as the oxidation gas.

• GC-Comb-MS ModeThe GC-Comb-MS mode is a configuration where an element-selective combustion unit is connected after the GC and before the MS. In this mode, oxygen/nitrogen-containing compounds can be selectively detected. After separating hydrocarbon compounds with GC, the compounds are oxidatively decomposed in the combustion catalytic reactor and detected using the SIM mode.

MS Chromatogram from GC-Comb-MS (Oxygen Content Analysis)

• (1) Cyclohexanone(8) Hexylbutyrate(2) 2-ethoxyethylacetate(9) Dodecane(3) Benzaldehyde(10) Phenethyl acetate(4) Dimethyl malonate(11) Dimethyl phthalate(5) 2-pentyl butyrate(12) Acephatene(6) Acetaldehyde(13) Dibenzofurane(7) 1-octanol(14) EicosaneNote: This provides a unique chromatogram that can be used to determine whether compounds contain oxygen.
  Compounds 9, 12, and 14 do not contain oxygen.

MS Direct Mode

The MS Direct mode is a common configuration in GC-MS. The ELEM-SPOT system enables analysis in a typical GC-MS setup without passing through the element-selective combustion unit by switching the configuration flow paths.

Securing a Seamless Workflow

• The GC-Comb-MS mode enables selective analysis of specific heterocyclic compounds with high sensitivity while the MS direct mode enables conventional GC/MS analysis. Each mode can be specified and controlled easily using the LabSolutions system control software, allowing both modes to be used quickly and conveniently for analysis.

• Automated Switching between Oxidation GasesIn GC-Comb-MS mode, Shimadzu’s unique GC gas selector can automatically switch between oxidation gases for trace analysis of either oxygen or nitrogen.

Simplified Routine Maintenance

• One-Step GC Injection Port MaintenanceSystems are equipped standard with ClickTek nuts that enable one-step maintenance of a sample injection port without using a tool to open/close the sample injection port.
• Easier Reaction Tube ReplacementThe reactor is oriented horizontally to provide easier access to the reaction tube and eliminate the need for reactor disassembly for the tube replacement.

Supporting Cutting-Edge R&D

The ELEM-SPOT system can provide analysis results that are essential for researching and developing biomass, chemical recycling, and other solutions for achieving a carbon-neutral society.

• Analysis of Oxygenated Compounds in Wood Bio-OilBiomass used as a raw material for bio-oils can contain large amounts of oxygenated compounds that can damage the catalysts used during oil purification. Therefore, such compounds must be identified and removed.
• Changes in the Catalytic Ability of Hydrotreating Phenols Over TimeNote: As the continuous usage time of the catalyst increases, it can be seen that oxygen-containing components such as phenols are not processed.Because the ELEM-SPOT system can uniquely identify oxygenated compounds in countless matrices, it can be useful for quickly checking the effectiveness of oxygenated compound removal capacity over time.

Analysis of Nitrogen-Containing Compounds in Bio-Oils Derived from Algae

Algae, which has attracted attention as a raw material for bio-oils, contains many nitrogen compounds. However, nitrogen compounds can affect catalytic performance during hydrogenolysis, so they must be appropriately treated before bio-oil purification. Shown above is a chromatogram of bio-crude oil derived from algae and a chromatogram of specifically detected nitrogen compounds in crude oil. In addition to oxygenated compounds, the ELEM-SPOT system can specifically detect compounds that contain nitrogen atomic configurations.

“Smaller, simpler, and easier to use – without compromising performance.” That’s the demand from analysts. And that’s why Shimadzu developed the Brevis GC-2050. This new space-saving GC delivers uncompromising analytical performance in a modern yet rugged design, easily meeting the analysis needs of laboratories in a range of industries.

Windows is either a registered trademark or a trademark of Microsoft Corporation in the United States and/or other countries. Chromeleon is a trademark of Thermo Fisher Scientific Inc. and its affiliated entities.
OpenLab is a trademark or a registered trademark of Agilent Technologies, Inc. in the United States and/or other countries. Empower is a trademark of Waters Corporation and its affiliated entities.
Brevis, AOC, ClickTek, LabSolutions, Analytical Intelligence logo, i-PeakFinder, and Nexis are trademarks of Shimadzu Corporation or its affiliated companies in Japan and/or other countries.

Compact without Compromise

Space-saving yet expandable design

• The compact Brevis GC-2050, with a 350 mm system width, including an auto-injector (AOC-30i), makes even more use of lab space. Compared to the flagship Nexis GC-2030, the system’s width has been reduced by approximately 35 %. At the same time, it is possible to connect additional headspace samplers, a mass spectrometer, and other accessories (available soon), providing the scalability to cover the analytical needs of today’s GC/GCMS users.

Sufficient GC oven size

• Despite its space-saving design, this GC oven does not require a dedicated column, and up to two general capillary columns can be used.

Remote Display

• Even without a monitor on the Brevis GC-2050, you can use the GC Remote Display installed on a PC or tablet to monitor the device status and perform operations.Note: Only one Remote Display can be connected to a single GC at a time.
  Connection Method: LAN / USB cable.

Compact and easy to maintain

①One-touch inlet maintenance

The injection port can be opened or closed without tools by simply sliding the ClickTek Nut lever. Replace the insert, slide the lever, and feel the click to ensure leak-free performance.

②Fast inlet maintenance, Easy sTop

Clicking the Maint. (Maintenance) button on the GC front will start lowering the temperature of the GC inlet and oven, and stop the gas supply automatically*. After maintenance of the inlet, clicking the button again will return the instrument to standby after an automatic leak check. Routine maintenance procedures can be further simplified.

Note: Disabling the automatic gas supply shutdown to protect the MS detector is possible.

③Tool-less column installation

The ClickTek makes column attachment a one-touch operation. A noticeable clicking sensation signals a secure column connection, putting the user at ease.

Note: The ClickTek connector is optional.

Less Energy and Gas Consumption

ECO design

The Brevis GC-2050 consumes 30 % less power than conventional GCs. It also minimizes helium usage and supports operations with alternative carrier gases.

• Comparison of power consumption on a GC run cycle.
  *Comparisons were made under the following analytical conditions.SPL: 270℃, FID: 270℃,
  Oven: 50℃ → (10℃/min）→250℃（10min Hold）→（Cooling）→50℃
  *The amount of electricity consumed will vary depending on the laboratory environment.
• High-performance insulating materials and a smaller oven have eliminated heat loss. As a result, the Brevis GC-2050 achieves about a 30 % reduction in power consumption during analysis compared to conventional GCs.

Safer and even faster analysis with H₂ gas

• High-speed analysis of impurities in benzene using hydrogen carrier gas

• The Brevis GC-2050 can be equipped with a hydrogen sensor. Not only does it enable early detection of potential leaks in the oven and maintain a safe standby mode, but if a hydrogen leak occurs, it turns off the main power to prevent an accident. In addition, the GC main unit has an automatic carrier gas leak check function that supports the use of hydrogen carrier gas. Furthermore, a gas selector* can switch the carrier gas to nitrogen after an analysis has been completed to enhance safety. Hydrogen carrier gas enables fast analysis (application example above) and maximizes throughput in the laboratory.* Hydrogen sensor and gas selector are options.

Built-in Analytical Intelligence

Automatic remote operation

• With Remote Display and LabSolutions Direct, GC systems can be accessed from anywhere with a smart device or a PC, dramatically improving the analysis workflow and enabling new ways of working.

Automating the Procedures of Experienced Analysts, Clean Pilot　

• Baselines can be unstable during GC startup. The Clean Pilot feature provides quick and efficient automatic conditioning to provide stable analytical results while reducing the burden on laboratory personnel.

Analysis Starts Immediately under the Optimal Conditions, Automatic Start and Stop Function

The Brevis GC-2050 automatically performs gas and temperature control, allowing the system to shut down and start up unattended. When not performing analysis, the system can be shut down to reduce unnecessary power and gas consumption, thereby reducing running costs.

Supply Gas Check　

• When connecting a main and a spare gas cylinder to the gas selector (option), the gas selector will monitor the main gas cylinder pressure and automatically switch the gas supply to the backup line when the cylinder becomes empty. This prevents problems before they occur and allows you to continue analysis with peace of mind.

Enabling Remote Control and Monitoring, LabSolutions Direct

• Remote operation and monitoringLabSolutions Direct, a standard feature of LabSolutions, allows you to monitor instrument status and chromatographic signals, start and stop the instrument, and start the analysis from a web browser on a PC or smart device at a remote location.

Making Routine Analysis More Convenient

2D Code Navigation

When a smart device reads the code or clicks the URL link on a PC, a solution, including procedures or videos, is presented for a quick recovery.

Best-in-Class Performance

Outstanding Analytical Reproducibility

The Brevis GC-2050 provides best-in-class analytical precision. The latest auto-injector, AOC-30i, enables continuous analysis with a high level of precision that cannot be achieved with manual operation. In addition, the flow controller (AFC) with a built-in CPU supports constant linear velocity, constant flow rate, and constant pressure control of carrier gas to achieve outstanding analytical reproducibility with ultra-high speed and ultra-precise control.

• Continuous analysis of the Grob Test Mixture

Column replacement is a breeze with the Shim-pack NT-ODS slide-in column. Simply slot the monolithic column into place and it connects automatically, with no need for any tools and no risk of human error.

Remote data monitoring allows more flexibility in scheduling and work from home possibilities.

Intuitive to operate

Hardware and software advances in HPLC over recent years have led to a fully-automated analysis cycle as standard. However, column installation has remained a manual step requiring user know-how. With the LC-2030C NT we introduce a dedicated slide-in column, the Shim-pack NT-ODS. The user can simply insert this column into the front slot and it will be automatically incorporated into the flow path. Analysis can then be begun from the LCD touch panel. The whole procedure can be carried out by staff without specific training. Equipment status and chromatograms can be monitored from outside the lab during analysis, and data results can be processed remotely through a networked PC, opening up more possibilities for flexible workplace.

Consistent data between users

Column connections can affect the shape of chromatograms, either through small differences between users or human error. Since the Shim-pack NT-ODS is connected automatically by the instrument, there is no need to worry about these possible effects.

Stable column performance over a large number of samples

The dedicated Shim-pack NT-ODS is a monolithic-type column. The packing state of its separation medium is maintained over a long continuous analysis, whereas a particle-type column may deteriorate. The Shim-pack NT-ODS therefore provides long-term stability even over a large number of continuous injections.

Shim-pack NT-ODS is a silica-based monolithic column with both macropore (µm) and mesopore (nm) structure. The macropore structure helps to avoid column clogging, resulting in long-term stability. The well-designed chemical structure of the stationary phase provides superior reproducibility.

Switch back to analysis with conventional methods

The Co-Sense series features automatic sample processing systems intended to improve the efficiency of LC-MS operations by automating complicated sample processing steps. This eliminates the need for tedious, time-consuming, and expensive manual processes. It also achieves parameter settings for separating target components by HPLC can be set freely without being encumbered by LC-MS limitations. The Co-Sense series is especially well suited to the structural analysis of impurities in pharmaceuticals. It is also advantageous for LCMS measurement in the life sciences or chemical industry fields, such as to research metabolites in biological organisms or to analyze the side reaction in chemical synthesis.

Co-Sense Series Features

Full Automation of Sample Processing

All sample processing steps are automated, from introducing the sample, purifying target components, concentrating, and desalting, to solvent replacement and collecting fractions in NMR sample tubes or delivering the sample to an LCMS system. Consequently, it not only increases productivity, but also eliminates operator errors inherent in manual processes. Also, since samples are processed serially online, even unstable samples can be measured reliably.

Improved Measurement Sensitivity

Because target components can be concentrated to levels several times to several tens of times that of conventional LC-NMR and LC-MS systems, NMR and MS spectra with high S/N ratios can be obtained in a short time and measurement throughput is increased.

Optimized HPLC Conditions

Since separation by HPLC is not dependent on NMR measurements, optimal separation parameters can be specified. Therefore, there is no need to evaluate parameters based on NMR considerations. This reduces the amount of work involved in setting parameters.

Easier to Operate

Systems are controlled using software with a graphical user interface. This makes the software easy to operate and allows confirming the system operating status at a glance.

Reduced Solvent Consumption

The Co-Sense for LC-NMR system uses normal inexpensive solvents for fractionation processes, which can consume large amounts of solvent. In contrast, it uses only small amounts of expensive deuterated solvents, which contributes to operating cost reduction.

The name “Co-Sense” means a collaboration of senses, which is the concept of the product. It represents the user and manufacturer working together to create new value.

System Variation

• Co-Sense for Impurities

Analysis of ultra-trace impurities or components in complex matrices

• Co-Sense for BA(biological sample analysis)

nalysis of low molecular weight compounds in biological samples

• Co-Sense for LC-MS

Structural Analysis of impurities using Mass spectrometry

The i-Series Method Transfer System (MT system) enables both conventional analysis via its high compatibility with existing LC systems and rapid analysis via high-speed methods.In pharmaceutical development, a single integrated system allows process synthesis screening analysis for synthetic substances in the UHPLC flow line, and impurity content identification in the HPLC flow line.

Analysis results from LC systems in the same laboratory may differ, even with the same method, due to differences in the system delay volumes of these systems. The i-Series MT system demonstrates outstanding reproducibility between various LC systems with different system delay volumes, simplifying method transfer between instruments.

Further more, with the i-Series MT system the process of migrating from UHPLC to HPLC or from HPLC to UHPLC can be accomplished using a single system.

The i-Series MT system is based on the same user-friendly i-Series, but maximizes performance and reliability for migrating and transferring customer methods.

Dual Flow Lines Simplify the Process of Migrating Methods

A single integrated system allows analyses in two flow lines with UHPLC and HPLC delay volumes. In addition to simplifying the transfer of analytical methods for customers using HPLC, it can also streamline the process of converting customers’ analytical methods from HPLC to higher-speed UHPLC.

Supports Method Compatibility Compliant with the United States Pharmacopeia

General Chapter <621> Chromatography in the United States Pharmacopeia specifies allowable ranges for changes to analytical parameters, so that revalidation is not necessary as long as the setting values remain within those allowable ranges. i-Series MT system includes dual flow lines for HPLC and UHPLC analysis. With two system volumes, it can support both existing analytical methods and UHPLC methods.

ACTO Function Achieves Higher Reproducibility

The newly developed Analytical Condition Transfer and Optimization (ACTO) function incorporated in LabSolutions allows users to transfer injection timings matched to differences in system volumes between instruments, without editing the concentration gradient programs in existing methods.

More Optimal Method Transfer with a Simple Operation

Reproducing analysis results is difficult even when the same columns and the same mobile phase conditions are used, because the gradient analysis start times differ due to differences in internal volumes between LC systems. With the ACTO function, differences in internal volume can be fine-tuned to heighten data reproducibility between different systems and streamline method transfer.

Achieves Seamless Method Transfer Process

Transfer Methods with a Single Button Operation—ACTO Function

The ACTO function also includes functionality for transferring HPLC methods to UHPLC methods. Just by loading method files prepared on an existing system and entering information about the columns used, the optimized methods will be presented for fast analysis. By selecting one of the flow lines, the function can also transfer methods from UHPLC to HPLC.

The i-Series MT system has two flow lines matched to the UHPLC and HPLC delay volumes. In addition to simplifying method transfer for customers using HPLC, this single integrated system also streamlines reviewing procedures for increasing the speed of customers’ methods using UHPLC.

Designed for User-Friendly Operability

—Core Technologies That Provide a Solid Foundation for Analysis

Nexera FV

Dissolution tests are widely used in original pharmaceuticals development and quality control and for bioequivalence tests in generic drugs.

The Nexera FV provides substantial labor savings by automating processes ranging from the dispensing of dissolution media to data acquisition and data analysis.

In addition, the system is based on the Nexera X3, renowned for its speed, sensitivity, and stability. Now you can quickly obtain reliable dissolution test results. The Nexera FV can also be used as a standard UHPLC system, ensuring high laboratory throughput.

-Provides Labor Savings and Faster Speeds in Dissolution Testing-

System Configuration for Online Dissolution Testing

With the Nexera FV, the dissolution tester and the autosampler are connected online, so everything is automated from sampling to dilution to data acquisition and analysis. As a result, there is less test-related work for the operator, and a subsequent increase in processing throughput.
In addition, there is no manual dispensing of samples, ensuring reliable results.

Flow Vials Provide Automated of Dissolution Testing

A dissolution medium from the dissolution tester flows directly into flow vials loaded into the autosampler. A bubble suppression design has been adopted for these flow vials, enabling high-accuracy sampling of dissolution media.
Depending on the dissolution tester used, 8 or 12 flow vials can be loaded. Further, since the flow vials are purposefully designed not to control the temperature, salt precipitation from the dissolution medium is suppressed.

-Enables Testing of Quickly Dissolving Samples-　　　　　　　　

Two Analysis Modes Promote Faster Dissolution Testing

Direct Injection Analysis Mode: Exclusively with the Nexera System

In this mode, the dissolution medium delivered from the dissolution tester is directly loaded and analyzed. This is effective if the analysis of the number of vessels finishes before the next sampling interval.
This analysis mode can be selected precisely because the Nexera FV is compatible with UHPLC analysis.

Fraction Analysis Mode: For Confirmation of Dissolution Profiles at Short Sampling Intervals

This analysis mode is used for tests in which the sampling interval is short. This is suitable when checking the dissolution profile of instantly soluble samples. The Nexera autosampler’s high-speed performance makes this system compatible with sampling intervals as short as five minutes. In addition, up to 768 samples can be fractionated, making this mode effective when the dissolution quantity is large and dilution will be required.

Reliable Performance Expands the Range of Choices

Compatible with High-Concentration Samples Requiring Dilution

High dissolution quantity samples often require dilution. Samples can be diluted by using the fraction analysis mode. High injection accuracy is provided even at trace quantities, enabling reliable dilution even without manual handling.
The data shows a comparison between a standard liquid (aqueous caffeine solution), with the dilution ratios manually adjusted by an experienced engineer, and a standard liquid automatically diluted by the Nexera FV. This data shows that the system can perform dilution reliably.

One System Plays Two Roles, Significantly Improving the Throughput of the Testing Lab

The Nexera FV is a multipurpose system for on-line dissolution testing and high-efficiency UHPLC analysis, such as compound screening, and everyday method development applications. This significantly increases the system operation rate in the laboratory.

Long-Lasting Consumables Provide for High Cost-Effectiveness

A special septum is used for the flow vial that receives the dissolution medium. It boasts a better degree of adherence after needle penetration in comparison to a regular septum, and can be used for 100 continuous injections without leaking. This greatly reduces maintenance, enabling continuous testing.

-Substantial Improvements in Work Scheduling-　　　　　

Special Software Makes Testing Preparation More Efficient

DT-Solution Software Supports the Creation and Implementation of Test Schedules

With dissolution tests, one of the most labor-intensive processes is establishing a batch schedule for the test. The custom DT-Solution software eases the burden. With this software, the user can configure all the required information in a single window. Then, click a single button to automatically generate a batch schedule in LabSolutions software so that testing can start. In dissolution tests performed with the Nexera FV, preparation time is minimal.

Rapid Confirmation of Test Results and Automatic Generation of Reports

The browser function built into LabSolutions is convenient for assessing changes in the chromatogram over time. Multiple data sets can be displayed simultaneously in a single window, so the data can be compared at a glance. In addition, the creation of reports on can be completely automated with the multi-data report function. When the test finishes, a result table, pivot graphs, and test pass/fail judgments for each component are created automatically, so the test results can be rapidly confirmed.

Streamline and Simplify Establishing the Conditions for Preparative Work

Nexera Prep System

Streamline development of Analysis Conditions and Optimization of Preparative Parameters

In order to separate multiple components, the analysis and fractionation parameters must be optimized, which involves a great deal of work.
Shimadzu provides the Method Scouting system, which investigates conditions at the analytical level. Method Scouting system fully automates method scouting in which combinations of mobile phases and columns are automatically changed, equilibrated, and evaluated, allowing efficient method development.
Further, the preparative system performs automatic simulations using the pre-preparative results, enabling optimization of the fractionation parameters.
This reduces the work involved in investigating conditions, which saves on mobile phase solvent and samples.

Development of Analytical Conditions (Method Scouting System)

A development is performed to separate the target compounds at the analysis level.
Using the Shimadzu Method Scouting system together with Method Scouting Solution, a special software program, provides a fast and accurate method scouting workflow, which supports heightened efficiency in method development.

Significantly Reduces the Process of Setting Fractionation Parameters

Simple parameter setting by fraction simulator

LabSolutions software provides simulation functions that reduce the labor involved in investigating conditions for analytical and preparative work.
With the LabSolutions fractionation simulator (patent pending), specify the peak segment in the chromatogram to fractionate, and the system automatically sets the parameters required for fractionation. This reduces the time spent on setting fractionation conditions to about 1/4 the typical expenditure.

Noise skipping by new algorithm

When configuring fractionation via automatic peak recognition, noise in the chromatogram is sometimes mistaken for component peaks, resulting in an insufficient number of test tubes for intended collection or improper positioning of collected fractions. With the LabSolutions software Peak Sensitivity Determination function (patent pending), peaks are recognized from the number of data points consecutively exceeding the configured threshold value, to determine whether to fractionate.

Fraction Purity Checks（LH-40）

A fraction purity check can easily be performed with a single system. Purity checks can be performed without changing the fraction recovery container, so the workload is reduced and throughput is improved.

Sample Rescue Function Prevents the Loss of Precious Samples (LH-40, FRC-40)

Even if a problem occurs during preparative work, the sample remaining in the system can be recovered. By following the rescue instructions, the precious sample is recovered into the specified container rather than being discarded. Additionally, by using the optional waste collector, samples that cannot be recovered due to fractionation mistakes can be retained.

• Fraction Collector

Preparative Work for Target Components at High Purity Levels and High Concentrations

Equipped with Technology for the Trap Enrichment of Target Components

Nexera UFPLC, Ultra Fast Preparative and Purification Liquid Chromatograph System

Significantly Reduces the Processes Involved from Preparative Work to Purification (Free basing Treatment) and Powderization

The ultra fast preparative and purification liquid chromatograph system, Nexera UFPLC, streamlines purification operations by automating the preparative process from separation to concentration, purification, and collection.
In conventional preparative LC, the amount of fraction is diluted with the mobile phase, resulting in a huge volume, which takes time to evaporate, and post-treatment work, such as removal of salts derived from the mobile phase, is required. Nexera UFPLC concentrates target components by using a trap column. In addition, salts derived from the mobile phase and counter ions of the target compound are removed. Furthermore, because organic solvents are used to elute the target components,the time for evaporation can be significantly reduced.
Nexera UFPLC can also be used for standard preparative chromatography by collecting the fractions directly without any concentration steps.

Automation of the Preparative Purification Process

When target compounds are to be powderized, this process can be hindered by a number of factors including the presence of acids, salts, and refractory solvents. With the UFPLC Ultra Fast Preparative and Purification Liquid Chromatograph, these hindrances to powderization can be removed by flushing them out using a trap column, allowing a high purity powder of the target component to easily be obtained by anyone.

Even Trace Components Are Recovered at High Concentrations

Normally, when preparing trace quantity target components, preparative work involves injecting the sample multiple times to obtain sufficient amounts of the target. As a result, the volume of fractionation liquid ultimately obtained increases in proportion to the number of injections, increasing solvent use and dry down time. With the UFPLC Ultra Fast Preparative and Purification Liquid Chromatograph, even with multiple injections, the fraction of the target component is injected into the same trap column for enrichment. The final volume of fractionated liquid from the trap column is minimized, exchanging the weaker loading solvent for a suitable organic solvent. The target component can then be recovered at high purity levels and at high concentrations.

Purification Solution Simplifies Settings Related to Preparative Purification

The special Purification Solution software is equipped with peak tracking functions that enable the target peaks and fractionate and be checked at a glance.

Various Fractionation Modes

To ensure that valuable samples are fractionated, Purification Solution offers three fractionation modes.

Automatic Removal of Non-volatile Salts

In the conventional preparative LC, salts derived from the mobile phase are included in the recovered product. With Nexera UFPLC, salts derived from the mobile phase can be removed on the trap column.
In the picture below, Ibuprofen was prepared using a solvent containing ammonium chloroacetate, a non-volatile salt. With conventional preparative LC, ammonium chloroacetate precipitated at the same time during evaporation. However, ibuprofen was recovered as a single component with Nexera UFPLC due to the use of a trap column.

Concentration and Powdering of Target Ingredients in a Short Period of Time

Using Nexera UFPLC, samples are repeatedly injected and the target components are introduced into the same trap column, allowing concentration on the trap column (up to 100 mg capacity). After concentration, the target component is eluted with an organic solvent, allowing recovery of the target component at a high concentration and shortening the time for evaporation. The volume of recovered liquid and the time required for evaporation were measured when 100 mg of the target component, ibuprofen, was purified by trap purification. Compared to the conventional preparative LC process, the overall time was reduced by 50%.

Counter Ions Removal

In some cases, basic compounds can contain counter ions (such as trifluoroacetic acid, TFA) derived from both reagent and mobile phase. These components may remain as impurities, affecting the final purity. With Nexera UFPLC, the target component can be recovered as a high-purity free base (free base type) by using a trap column.

Structural Analysis without Preprocessing

The ¹⁹F NMR spectrum of a 0.1% TFA solution containing propranolol after freebasing treatment is shown. Compared to the untreated sample, the TFA-derived peak in the fractionated sample is significantly smaller, confirming that TFA is effectively removed in the purification process using Nexera UFPLC.

Preparative Work for Non-UV Absorptive Components

Capable of High Purity Preparation Triggered by up to Four Detector Channel Signals

Nexera Prep LC/MS Preparative System

Using MS Signal Triggers Enables Recovery with no Target Fraction Omissions

It can be difficult to prepare low UV absorptive components using just a UV signal as the trigger, so there is a risk that the fraction will be missed. By using the MS signal as the trigger, the preparative work can be performed simply, with nothing missed. By specifying the m/z of the target component, fractions can be collected with confidence. The LCMS-2050 mass spectrometer enables high-sensitivity and high-resolution detection for preparative work with no target components omitted.

Purification of Un-separated Target Components

Two specific m/z values (from the target component and its impurity) were simultaneously used to obtain an “high-purity” fraction, even in the case of incomplete chromatographic separation.

Flow Splitter for Fractionation Triggered by LC/MS Signals

For fractionation triggered by LC/MS signals, a portion of the sample must be introduced into the LC-MS.
The dedicated flow splitter splits a small portion of the flow from the preparative stream to the MS stream. This enables the use of LC-MS detection signals for triggering fractionation while maintaining a high recovery rate.

Customized Detection Methods

Signals from various detectors can be used for triggering the fractionation. The optimal system configuration can be obtained for different samples and conditions.

Increased Efficiency from Preparative Analysis Setup to Data Processing

Open Solution Software for Preparative Systems

Open Solution is open access software that not only streamlines preparative purification operations, but also supports multi-user operation of preparative systems. Even inexperienced users can perform routine preparative operations easily with minimal efforts.
The use of a network contributes to improved work efficiency.OpenSolution

Easy Operation, Screening Using Multiple Conditions

After logging into Open Solution, analysis can be started from a single screen by simply selecting a pre-registered method and registering a sample. Screening analysis can be easily performed with the same procedure. While the system is performing an analysis, a different user can schedule the next analysis.
Open Solution software will automatically include washing steps between different user methods, reducing the system downtime.

Confirmation of Fractionation and Re-injection Analysis

By selecting the vial displayed in the fraction collector diagram, the chromatogram, mass spectrum, and UV spectrum of that fraction can be easily confirmed. From the same screen, it is possible to directly check the purity of the fraction.

Automatic Scale-up from Analytical Scale to Preparative Scale

When screening analysis is performed to examine preparative conditions, the results are judged in three steps according to the degree of separation and MS spectral purity. If the judgment is acceptable, a preparative method is automatically generated. Therefore, the user can focus on examining conditions for samples with insufficient separation or aren’t detected.

Remote Data Processing

After data acquisition, the system sends an e-mail notification with a link to the data storage location and a report. Therefore, data processing can be performed immediately. In addition, data analysis can be performed from a remote PC by utilizing the network.

High Separation via Preparative Recycling

Components Difficult to Separate can be Recovered at High Purity Levels and at Low Cost

Recycling Preparative System

What is the recycling separation method?

Because long preparative columns are expensive, there is a need to use comparatively lower cost short columns.
In the recycling separation method (closed valve recycling), the eluate liquid containing the target components that has eluted from the separation column is recycled into the column, enabling an equivalent separation capacity to that of a longer column.

The figure below shows the results of a seven-cycle recycling separation. In the first injection (typical separation), the separation of the two components is insufficient (red area). However, when the column eluate is returned to the column from the detector, it is separated a second time. If this recycling is repeated, the results obtained are equivalent to connecting a number of columns in series corresponding to the number of repetitions. In this example, a 4.0 or better resolution was ultimately obtained with seven recycling separation cycles (blue area).

Example of the improvement in separation by recycling : The coeluting peaks (red) are completely separated (blue).

Flowrate : 10 mL/min
Detection wavelength : 254 nm
Column : Shim-pack PREP-ODS(H) 20 mm I.D. x 250 mm L.
Mobile phase : Water/methanol = 1/9 (v/v)
Sample : Mixed 1% n-butylbenzene/iso-butylbenzene solution

Recycle-Assist* – Special Preparative Recycling Software

Perform Automatic Preparative Recycling with a Simple GUI-Based Operating Environment

The graphical user interface (GUI) provides an environment where even novices to preparative recycling can perform operations simply and reliably. A single main window is used for the workflow from recycling to fractionation, thus reducing the risk of wasting precious samples through setting mistakes.

Recycling Conditions are Completely Set in Three Steps

Just click three points corresponding to the recycling start, recycling stop, and automatic collection start point to complete the settings for the recycling preparation conditions. Entering complicated numerical parameters is completely unnecessary, so recycling preparative work can start easily.

* This is compatible with the FRC-10A

Excellent System Expandability

System Configuration Applicable to a Variety of Applications

Solvent Delivery Unit Accommodates a Wide Range of Recovery Volumes

Solvent Delivery Unit Accommodates a Wide Range of Recovery VolumesShim-pack Scepter ColumnsThe LH-40 Liquid Handler, Combination of Autosampler and Fraction CollectorFRC-40, Highly Flexible Fraction Collector

The Nexera UC Prep is a new preparative supercritical fluid chromatography (SFC) system that offers both the high basic performance developed for the previous Nexera UC model and original state-of-the-art preparative SFC technologies. It resolves a number of issues in preparative tasks, reducing labor and improving efficiency while fitting into pre-existing workflows. Not only does the Nexera UC Prep achieve superior recovery rates for purification, it provides flexible system configurations in a compact design, requiring low installation space and allowing you to maximize lab resources.

Unique technology achieves higher recovery rates

SFC shortens analysis times

Due to the low viscosity and high diffusivity of supercritical CO₂, column back pressure for supercritical fluid chromatography supercritical fluid chromatography (SFC) is low even at high flow rates which enables faster analysis without sacrificing column efficiency. This allows significantly shorter analysis times than HPLC.

In purification using SFC, the target compounds are recovered in high concentrations in an organic solvent, which saves time not only during analysis, but also during post-run processing after preparative tasks are complete. The Nexera UC Prep maximizes fractionation output with its high recovery rates and ability to carry out continuous preparative work that further shortens the user’s waiting time.

High recovery rates

In preparative SFC, one factor that results in lower recovery rates is increased scattering of the eluent when the CO₂ returns from a supercritical to a gaseous state. The Nexera UC Prep’s patented gas-liquid separator, the LotusStream separator, successfully reduces sample dispersion and carryover, while also achieving high recovery rates. These high recovery rates can be obtained regardless of flow rate or modifier concentration, even for volatile compounds such as the fragrance linalool.Comparison for 1% linalool

LotusStream separator (patented technology)

Decreases flow rate without increasing the pipe diameter by splitting flow through multiple channels. The CO2 is discharged externally while the liquid travels along the column and drips directly into the collection vessel without dispersing or spattering the eluate.

Direct fractionation into vials

Direct fractionation into 96-well plate

Stacked injection function eliminates waiting time

Normal injection wastes time between peak elutions. Using the Nexera UC Prep’s stacked injection function, samples can be injected continuously without any waiting time, enabling more samples to be processed. Settings for this function can be specified easily in the dedicated software Prep Solution.

Simple post-run processing

Because most of the mobile phase is vaporized supercritical CO₂, only the organic solvent (modifier) added to change the polarity of the mobile phase remains after preparative work. Since there is no water content in the recovery fraction, the concentration time is significantly shorter.

Solid autosamplers for increasing loading capacity

More of the target compound can be fractionated at once by loading a large volume. However, this can sometimes lead to poor separation and broad peak shapes because of sample solvent effects. By performing fractionation with the on-line SFE-SFC, solid samples can be enclosed in an extraction vessel and extracted directly without dissolving in a solvent. A good peak shape prevents simultaneous elution of contaminants and improves the purity of the target component.

Chromatogram of ketoprofen (5 mg) loaded

Prep Solutions enables a seamless preparative workflow

The dedicated software, Prep Solution, ensures that it is simple to scale up from an analytical to a preparative workflow, and makes it easy to configure parameter settings. It greatly increases the efficiency of preparative workflows.

Easy to understand even for first-time users

The parameter settings in Prep Solution have been kept as concise and intuitive as possible, so that all users can operate the system with minimal training. This also avoids the risk of wasting samples through human error.

A trial analysis, or scouting run, prior to fractionation confirms component peak shapes and retention times. Analysis can be started by simply inputting basic parameters in the three onscreen tabs.

The chromatogram obtained from the single analysis can be displayed in the simulation window, so that the collection start and stop times for each fraction can be selected with just a few mouse clicks. These settings can be applied to methods automatically.

Samples are fractionated based on the user-selected parameters. The fraction range is displayed on the chromatogram, which can be checked in real time.

Parameter settings for fractionation and injection can be adjusted during stacked injection (“on-the-fly” function).

Compact, benchtop design

This space-saving benchtop model includes a carbon dioxide pump that does not require an external chiller (cooling system for cooling system for heat generated when pumping CO₂ at high flow rates). In addition, one unit can handle a wide range of flow rates, lowering installation costs.

Benchtop system that can be installed anywhere

Usually a chiller is required to cool the solvent delivery pump when pumping CO2 at high flow rates. However, the Nexera UC Prep features a compressor-type cooling unit, reducing the size of the system and allowing it to be installed anywhere. Its footprint is equivalent to an analytical scale SFC system.

Wide range of flow rates available

In a single system, the Nexera UC Prep can handle ow rates from 10 to 150 mL/min for fractionation of a range of sample sizes, from a few hundred mg up to a few grams. Shimadzu provides various preparative systems, such as Nexera UC/s, which can perform SFC analysis and UHPLC analysis using a single system. The system corresponding to the application can be selected.

Add fractionation capabilities to the analytical SFC system

By adding a fraction collector to the analytical scale SFC system, it is possible to upgrade to a small-volume preparative system. A complete workflow can be carried out seamlessly on one system, from method development to fractionation.

Shimadzu’s unique LotusStream separator allows fractionation of small volumes, even into vessels such as 1.5 mL vials, without scattering of the solvent.

Small volume fractionation

Fully automated on-line extraction and fractionation

Nexera UC on-line supercritical fluid extraction (SFE) , SFC is a revolutionary system that combines on-line SFE, SFC and, fraction collector in a single flow. Target compounds are extracted from solid samples and then automatically transferred to SFC/MS so that no human intervention is required. The Nexera UC on-line SFE–SFC system reduces sample preparation time and acquires highly accurate data. Preparation can be carried out by connecting a fraction collector.

On-line Autpmation of theextraction and analysis of functional components in natural products

Target compounds are extracted from solid samples and then automatically transferred to SFC so that no human intervention is required. In the case of tomato paste, after preparing for analysis in as little as 5 minutes, extraction, separation, and detection of lycopene are automatically carried out. In addition to a shorter sample preparation, Nexera UC can automate the extraction, analysis, and fractionation process with the addition of a fraction collector.

On-line SFE–SFC technology achieves a high recovery rate

After placing the extraction vessel in position on the SFE unit and starting analysis in LabSolutions (analysis software), extraction and purification are performed seamlessly.
Online SFE–SFC enables the functional component “lycopene” to be automatically extracted from tomato paste. The amount of extracted lycopene is equivalent to the value indicated on the product packaging.

Maximize fractionation output and labor-savings

On-line extraction, separation, and fractionation are possible by connecting a fraction collector at the end of the detector. Furthermore, scale-up from analytical to preparative scale increases the volume of fractions. The Nexera UC Prep SFE unit (maximum ow rate: 150 mL/min) with a preparative column enables high-volume extraction. On-line SFE-SFC can automatically run the extraction, purification and fractionation continuously day or night. The target compounds are recovered in high concentrations in an organic solvent, saving time during post-run processing after preparative tasks are complete.

Nexera UC reduces environmental impact

Comparison of costs and consumption of organic solvent for a single analysis by conventional normal-phase LC vs. SFC is shown below. By using SFC, the total cost of analysis is reduced by 87.6% and the consumption of organic solvent is reduced by 94.2%.

Higher resolution

Improved separation and detection capabilities result from the low viscosity and high diffusion coefficient of Supercritical CO₂. As shown below, Nexera UC demonstrates high-separation selectivity for isomeric compounds that are difficult to separate by conventional HPLC.

Comparison of separation acquired by Conventional HPLC and SFC

Ideal for simultaneous analysis of compounds with a wide range of polarities

SFC can achieve a wide variety of separation patterns. This allows comprehensive analysis of compounds over a wide polarity range not previously possible with HPLC.　Different separation methods are generally used for fatty acids, which are typically analyzed by GC, and glycerides, which are typically analyzed by HPLC. However, because supercritical carbon dioxide has properties similar to hexane, SFC is well-suited for analyzing compounds with different polarity, providing an ideal solution for the simultaneous analysis of fatty acids and glycerides.

Simultaneous analysis of fatty acids and glycerides by SFC

Sensitivity results from different separation modes in HPLC vs SFC

Supercritical CO₂ has unique properties different from liquid. Using SFC in front of a mass spectrometer offers greater sensitivity than achieved with LC/MS/MS.

Comparison of peak intensity detected by LC/MSMS and SFC/MS/MS.
(Sample: Prostagrandin D2 10 pg)

Automatically performs a variety of method scouting processes

The high-speed performance of SFC can shorten the time required for method scouting. The system automatically generates a large number of methods by utilizing combinations of up to 12 columns, four modifiers, and different ratios of modifiers to mobile phase. With UHPLC/SFC Switching system, screening by UHPLC and SFC can be carried out in the same batch. Moreover, Method Scouting Solution, optional software for method scouting, makes it easy to set up multiple conditions.

A screen shot of Method Scouting Solution for Nexera UC user interface.

Chiral analysis with Nexera UC Chiral Screening System

CHIRALPAK^® Series and CHIRALCEL^® Series columns (Daicel Corporation) for chiral analysis are capable of resolving a wide variety of compounds by showing complementary separation targets. The combination of the Nexera UC Chiral Screening System and these columns simplifies method scouting for chiral analysis.

Available for both UHPLC and SFC analysis using a single system : Nexera UC/s

Various methods are needed to separate chiral compounds, structural isomers, and other such substances in all sorts of fields, such as pharmaceuticals, foods, and environmental testing. Because supercritical fluid chromatography (SFC), which uses supercritical CO₂ as a mobile phase, exhibits different separation behavior than ultra high performance liquid chromatography (UHPLC), superior separation results can be quickly obtained during method development by screening with both SFC and UHPLC separation methods.

Using the System for Chiral Analysis

In this example, methods were scouted for two types of chiral standard samples using both SFC and UHPLC. UHPLC and SFC parameter settings in the method scouting software can be specified by clicking a button to switch between modes.

A comparison of SFC/UHPLC chromatograms using three different columns indicated that UHPLC parameters provided better separation for omeprazole and SFC parameters provided better separation for imdapamide. LabSolutions software makes it easy to compare chromatograms from multiple sets of data.

Small volume fractionation

Upgrade to Analytical Fraction System

By adding a fraction collector to the analytical scale SFC, small-volume fractionation is also possible. A complete workflow can be carried out seamlessly on one system, from method development to fractionation.

In preparative SFC, one factor that results in lower recovery rates is increased scattering of the eluent when the CO₂ returns from a supercritical to a gaseous state. The Nexera UC Prep’s patented gas-liquid separator, the LotusStream separator, successfully reduces sample dispersion and carryover, while also achieving high recovery rates. It allows fractionation of small volumes, even into vessels such as 1.5 mL vials. The optical isomers of linalool were fractionated with high purity.

Fully automated on-line extraction and separation

Nexera UC on-line SFE-SFC is a revolutionary system that combines on-line supercritical fluid extraction (SFE) and SFC in a single flow path (patented technology). Target compounds are extracted from solid samples and then automatically transferred to SFC analytical system so that no human intervention is required. The Nexera UC on-line SFE-SFC system reduces the time for pretreatment of samples and acquires highly accurate data. In addition, off-line SFE can simplify pretreatment over existing solvent extraction methods.

Comparison of QuEChERS sample preparation and Nexera UC in the analysis of residual pesticides

A typical sample preparation takes 35 minutes and requires several manual steps. With Nexera UC, the same sample can be ready for on-line SFE/SFC analysis in as little as five minutes with only a few simple sample preparation steps.

* “Miyazaki Hydro-Protect”, Patented in Japan No.3645552

Customized modules for Nexera UC based on Nexera technology

Supercritical Fluid Extraction Unit SFE-30A

This unit operates at a maximum temperature of 80℃ to allow faster and more complete extractions. Five types of extraction vessels (two sizes (5 mL, 0.2 mL)made of PEEK(maximum pressure 20MPa), three sizes (10 mL, 5 mL, 0.2 mL) made of SUS) can be chosen based on the sample and sample amount.

CO₂ Solvent Delivery Unit LC-30AD_SF / Back Pressure Regulator Unit SFC-30A

Stable baseline with low pulsation is realized by LC-30AD_SF with a built-in cooler for pump heads, which delivers mobile phases up to 5 mL/min at pressures up to 66 MPa. The low dead volume of SFC-30A (0.7 μL) allows a mass spectrometer to be directly connected to the SFC system without splitting so that higher sensitivity can be achieved.

Nexera UC reduces environmental impact

Comparison of costs and consumption of organic solvent for a single analysis by conventional normal-phase HPLC vs. SFC is shown below. By using SFC, the total cost of analysis is reduced by 87.6% and the consumption of organic solvent is reduced by 94.2%.