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Batch Chromatography: Hipersep® line

The Hipersep® line (High Performance Liquid Chromatography) systems streamline lab, pilot and large scale purifications for a broad range of products: peptides, chiral compounds, complex synthetic mixtures, natural extracts, etc.

With the Cyclojet® option, Hipersep® systems dramatically increase the throughput of chiral separations.

Hipersep® systems combine perfectly with Prochrom® Dynamic Axial Compression (DAC) columns to provide the highest chromatographic performance.

Hipersep Systems offer numerous features:

Fully automatic operation
Designed for continuous operation (24/7)
3 injection modes
Low pressure, high pressure and manual modes
Choice of elution methods:
Various modes including isocratic or gradient (linear or step) elution
Advanced fraction collection:
Multiple fraction collection
Smart collection functions
Optimized performance
High accuracy gradient.

Specifications

Hipersep lab scale product line

Hipersep®	50-80	80-110
Productivity range (g/day)	10-200	20-300
Prochrom® column diameters (mm)	50	80
Prochrom® column diameters (mm)	80	110
Flow rate (ml/min)	100-600	200-900
Max operating pressure (bar)	100	100 (for 80)
Max operating pressure (bar)	100	70 (for 110)
Number of fractions * optional	5 to 10 *	5 to 10 *
Dimensions W x H x D (cm)	88 x 123 x 70	88 x 123 x 70

Typical Hipersep LAB unit shown with a Prochrom® LC 110 DAC column

Gradient
The Hipersep® LAB is capable of performing ternary, binary, step or linear gradients. The gradient System provides accurate and reproducible blending for preparative chromatographic separations (0.5 to 1% in the standard version, 0.1% with optional high performance gradient system).
More information on Gradient Operations

Cyclojet® option
Cyclojet® is a discontinuous steady-state process designed for binary separations. Combined with the "Cyclo-Help" modelling software, it typically provides 2 to 4-fold productivity improvements over classical HPLC.

Hipersep pilot and industrial scale product line

Hipersep®	S	M	L
Productivity range (kg/day)	0.1 -5	0.2 -20	0.5 -40
Typical Prochrom ® column diameters (mm)	150	200	300
Typical Prochrom ® column diameters (mm)	200	450	600
Flow rate (l/h)	60 - 150	150 - 500	300 - 1000
Max operating pressure (bar)	70	70	70
Number of fractions (optional)	5 to 10 *	5 to 10 *	5 to 10 *
Dimensions W x H x D (cm)	195 x 175 x 100	225 x 195 x 110	225 x 205 x 160

Typical Hipersep® M unit shown with a Prochrom® LC 300 DAC column

High Performance Gradient

Mass-flowmeter controlled, the in-line mixing system ensures highest (± 0.1%) of composition of isocratic, step and gradient eluents.
More information on Gradient Operations

Cyclojet® Option

Cyclojet® is a discontinuous steady-state process designed for binary separations. Combined with the "Cyclo-Help" modelling software, it typically provides 2 to 4-fold productivity improvements over classical HPLC.

Fully Customized Systems

Novasep Process engineers can design cutomized units, ideally suited to your facilities and specific process needs.

Characterictics

A complete preparative Hipersep® pilot and industrial unit includes:

Prochrom column® skid
Solvent delivery module
Automation and control unit
Full cGMP documentation and IQ/OQ

Software

PLC controlled with PC user interface
Multiple safety levels
User friendly, designed for chromatographers and producers
Validated software compliant with 21 CFR part 11 and GAMP 4

More information on CHROMSOFT

Options

Explosion proof design
Injection pump with variable flow-rate
Backflush, recycling
Temperature control and heat exchanger
Additional detectors: pH, conductivity, RI
Cyclojet®
Automated wiped or falling film evaporators
Tanking and solvent recovery systems
In-line high pressure filters
High performance controlled gradient (for pilot and industrial units)
Full cGMP documentation and IQ/OQ (for pilot and industrial units)

Added Benefits

Novasep Process offers complete process development services, and provides guaranteed performance for the processes supplied. Custom purification (from kg to multi-tons) is available at Novasep Process' FDA-inspected facilities.

The Heart of the Unit: the Prochrom® DAC Columns

PROCHROM COLUMNS

MODEL	MAX BED VOLUME (L)*	PHOTO
LC 50	0.7	view
LC 80	2.2	view
LC 110	4.3	view
LC 150	8.0	view
LC 200	14	view
LC 300	32	view
LC 450	72	view
LC 600	127	view
LC 800	220	view
LC 1000	353	view
LC 1600	900	view

* Bed Length = 45 cm (indicative).
- For each model, several choices for the maximum bed length are available.
- Columns are typically available at 100 bar (1,450 psi), 70 bar (1,000 psi) or 10 bar (145 psi) pressure rating.
- Standard pressure rating: 70 bar (except for Hipersep® Lab: 100 bar)

More information on Prochrom columns

More information on Gradient Operations
Hipersep® units provide high performance blending ("gradient") capabilities, for the in-line preparation of binary or multi-component eluent mixtures, Gradient reproducibility and accuracy are very critical issues in liquid chromatography. Two gradient concept are used in the Hipersep® units : digital and analogue.

Digital gradient
It is based on the sequential opening and closing of on-off (membrane) valves specially designed by Novasep for short response time. The opening duration of a given solvent valve is proportional to the desired amount of the corresponding solvent in the mobile phase. An agitated mixing chamber of adjustable volume is used to reduce composition pulsations. Ternary or even more complex solvent mixtures can be prepared. Digital gradients are mostly used for small size laboratory units.
Analogue gradient
It is based on the use on analogue valves and mass flowmeters. Solvents are pumped simultaneously, the amount of each solvent being adjusted by means of an analogue valve and measured by a mass flowmeter. The real composition is known at any time (it is calculated from the mass flow information) and feedback signals are sent to the analogue valves so that the expected composition is achieved.
Analogue gradients are mostly used for medium and large size industrial units. Accuracy and reproducibility of better than +/-0.1% are commonly achieved.
- Automatic Fraction collection
  If a chromatogram were absolutely stable run after run, fraction collection could be simply based on time. It is known, however, that there are often changes from run to run and that a simple collection sequence based on time is not sufficient. Embedded in CHROMSOFT, a sophisticated algorithm analyses the chromatogram in real time and automatically recalculates collection points in case of drifting chromatographic profiles (intelligent fraction collection). A specific graphical interface allows the operator to easily select optimum fraction collection parameters.
- Smart fraction collection system
  - Based on time and/or detection threshold and/or slope
  - Based on volume
  - Based on time/volume after an event

More information on Prochrom columns

The Prochrom® DAC columns offer performance & reproducibility.
Novasep preparative HPLC systems are based on Prochrom® DAC (Dynamic Axial Compression) columns. Over 20 years of experience have been accumulated in the design of Prochrom® DAC columns. The principle of these columns is the use of a piston attached to a hydraulic jack. The piston is used to pack and unpack the column, and keep the chromatographic bed under dynamic (and adjustable) compression, ensuring highest efficiency and bed stability at any scale.

For applications requiring the use of soft and/or fragile packing materials, the concept of intelligent piston has been developed and patented. It prevents mechanical degradation of the particles. Bed compression is maintained constant, independent of swelling or shrinking of the bed. If the solvent conditions are such that particle swelling takes place, then the piston automatically let the bed expand to maintain constant compression.

All Prochrom® columns can be consistently packed with small particulate media (10 µm and less) to high levels of performance: column efficiencies of up to 60,000 theoretical plates per meter have been reported for columns of 800 and 1000 mm internal diameter (i.d.). This requires an even distribution of the liquid flow over the column cross-section (plug flow), at all sizes. Novasep engineers have modelled the flow pattern at the column ends and designed efficient flow distribution systems for optimum performance.
For even better control of chromatographic conditions, Prochrom® DAC columns are delivered with a temperature jacket and/or insulation.

More information on CHROMSOFT

The control software, CHROMSOFT, compliant with GAMP4 (Good Automation Manufacturing Practice) and CFR 21 Part 11 guidelines. CHROMSOFT can be customized on request. The various actions and levels of interaction with CHROMSOFT are protected by passwords. The basic functions controlled by CHROMSOFT include operation of the gradient, regulation of the pump(s) flow rate(s), monitoring of safety levels, batch management, acquisition of operating parameters (analogue and digital), communication with a DCS, etc. CHROMSOFT can also control ancillary equipment related to the chromatographic units (such as evaporators, multiple tank levels, etc.).

CHROMSOFT offers two modes of operation : Maintenance (or Manual) and Automatic.
In Automatic mode, operation of the unit is based on a Purification Recipe which contains information related to the injected quantity, run time, unit configuration, solvent composition and fraction collection.

Batch Chromatography : Hipersep