Batch Chromatography: Hipersep® line

In association with the Prochrom® Dynamic Axial Compression (DAC) columns, the Hipersep® line covers all needs for preparative high performance liquid chromatography, from laboratory to multiple tons production scale. Chromatographic bed length can be adjusted at will, to provide the optimum process performance and economy. Direct process scale-up is ensured with the DAC concept. The Automation & Control system of the Hipersep® units has been developed to address current validation requirements, including 21 CFR part 11 guidelines of the US FDA. It includes sophisticated algorithms derived from P.A.T. (Process Analytical Technologies) concepts for gradient operation, intelligent automatic fraction collection, safety, etc. Versatility and Adaptability   Novasep offers a large range of LC columns and systems, available for medium and high pressure applications. The product line extends from units for laboratory scale applications (gram quantities) to complete systems for very large size industrial processes (hundreds of kg/day). A complete preparative Hipersep® unit includes the Prochrom® Column Skid, the Solvent Delivery Module and the Automation & Control Unit. Standard lines of equipment provide performance at a highly competitive price without compromising quality.

Hipersep® systems can also be fully customized to specific process and site requirements of our Customers. Typical features such as gradient modes, temperature control, multiple detection, etc., are commonly provided. The characteristics of some standard units are given in the table. Any type of column design (pressure rating, configuration, etc.) can be made upon request.

The product line

PROCHROM COLUMNS	Hipersep UNITS
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	MODEL MAX FLOW RATE (L/hr) PHOTO  Hipersep® Lab 50 15 view  Hipersep® Lab 80 34 view  Hipersep® Lab 110 42 view  Hipersep® S 125 view  Hipersep® M 500  view  Hipersep® L 2000  view  Hipersep® XL 3500  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)

The heart of the unit: the Prochrom® DAC column offers 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.

Automation & Control.
 
Novasep units are available with different levels of automation and control. A standard industrial system utilises a Programmable Logic Controller (PLC) for direct control of the unit (open/close valves start/stop pumps, read analogue sensors, etc.) and a PC for the user interface.

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.

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.
  
  ( More information on Analogue Gradient)
  

Automatic Fraction collection