Patent Description:
It is known that biopharmaceutical liquids are in general obtained by cultures in a bioreactor and that they must then be purified to achieve the required characteristics of purity, concentration, absence of viruses, etc..

The purification is generally carried out by means of a succession of treatments such as clarification to eliminate the residues from the bioreactor culture and viral retention treatment sometimes followed by diafiltration treatment and concentration by tangential flow filtration (TFF). Other operations exist concerning purification, such as chromatography (XMO).

The purification treatments are essentially carried out by filtering operations in a circuit leading to a container for collecting the treated liquid. A number of types of container containing liquids can be connected to the inlet of the circuit, such as the source container that contains the product to be treated, but also the containers containing a cleaning liquid such as sodium hydroxide (NaOH), a rinsing liquid such as pure water or a buffer liquid such as a saline solution.

In addition to the container for collecting the treated liquid, various other containers for collecting cleaning, rinsing or buffer liquid, or for collecting residues, can be connected to the outlet of the circuit.

In a production context the liquid treatments can be carried out sequentially, the collecting container for the first treatment potentially becoming the source container for the next treatment, and so on until the last treatment is carried out.

These treatments are conventionally carried out in dedicated installations comprising stainless steel pipes and other parts such as tanks or housings for filters, which necessitate operations before and after the actual treatment, which are relatively onerous, in particular operations of cleaning after use.

Within the last few years, these treatments have alternatively been carried out in installations in which the components in contact with the liquid are single-use components. From document <CIT> such an installation is known for treatment by chromatography.

This installation comprises a device formed from a base, a press with two shells mounted on a front face of that base, a bag clamped between that press and a support plate fastened on one side of the base. The device has the form of a cart mounted on four castors. The device is also provided, at the bottom, with a closed bay intended to receive one or more tanks if necessary. A control panel is arranged at the top of the front face of the device.

On the front of the shells there are formed shaping channels which are recessed and which face each other to form pipes in the bag and, on the back of the shells are installed instruments among which are pressure sensors and pinch valves which are configured to pinch the pipes so as to prevent or allow the passage of liquid therein. The bag is provided with a plurality of connectors for liquid and a network for conveying liquid between those connectors including the aforementioned pipes. The support plate comprises two fastening heads on which a platform is adapted to be fastened so as to dispose thereon instruments for the treatment of the biological liquid. These instruments may for example be sensors measuring pH or conductivity.

This installation further comprises other devices, of the cart type, on which are disposed pumps, various containers containing for example rinsing, cleaning and/or buffer liquids, and/or an elution product or which are provided to receive a collection, a fraction or waste; other measuring instruments such as a product presence sensor, a debubbler (also called a bubble trap), pressure, pH and/or conductivity sensors; one or more filter components and a chromatography column; all these components being configured to be connected to the circuit of the bag.

From document <CIT> an installation is also known which comprises a first cart and a second cart which may be either apart or nested with one in the other.

Each cart is of parallelepiped general shape and is mounted on wheels in order to enable its easy movement within a production zone.

The first cart is open on one side and towards the ground, and its interior is hollowed to enable the nesting of the second cart. On the upper part of the first cart is a support platform adapted to receive re-usable components of the circuit and means for supporting the disposable components. Among the re-usable components carried by the platform is in particular a flow pump, a first pressure sensor and a control panel for controlling the pump. The platform is positioned at a sufficient height for the second cart to be slid under it and be positioned, at least partially, under the circulation pump when the carts are nested.

The second cart has a platform provided with an upper face on which are positioned disposable components such as filter components and re-usable components such as a second pressure sensor. This second cart furthermore has storage drawers adapted to accommodate collecting bags for the liquid or other containers such as bags for sampling or drainage.

A pipe is linked to a source bag containing the liquid to treat and comprises a component adapted to cooperate with the pump to make that liquid flow towards the filter components, passing via the pressure sensors. Another pipe is connected to the filter component to make that treated liquid flow towards the collecting bag positioned within a drawer.

The diversity of the treatments that may be performed on this type of installation is great, in particular depending on the selection by the user of the liquid to treat and on the degree of purity to obtain for the collected treated liquid.

This great diversity in the treatments imposes the use of numerous re-usable and disposable components that are different from one treatment to another. In particular, the number of filter components and the means for control and actuation that are associated with these components and that are provided to measure and monitor the parameters of the treated liquid can increase. Therefore, the arrangement of these filter components and means for control and actuation are required to be simple, convenient and flexible.

Another similar installation for the treatment of biological liquid is also known from <CIT>.

It will be noted for example that U. patent application <CIT> describes what is referred to as a continuous chromatography method and apparatus, employing several chromatography columns in turn and sequentially.

The invention aims to provide an installation enabling the simple, convenient and economical implementation of treatments for biological liquid.

For this, the invention concerns an installation for treating biological liquid by chromatography, generally extending in a longitudinal direction and comprising:.

characterized in that said chromatography columns are disposed relative to each other in a direction of extension generally transverse to said generally longitudinal direction of extension of said installation.

The installation according to the invention has an arrangement which first of all ensures a particularly compact setting in place of the chromatography columns with respect to the general extension of the installation.

In particular, the rather transverse arrangement of the columns relative to the generally longitudinal extension of the installation provides compactness that is all the more advantageous in that in the context of the invention it enables the floor space (also called footprint area) occupied by the installation, which is required to be set up in what are referred to as clean rooms, with particularly severe sanitary constraints. Such a substantially transverse arrangement of the columns is moreover achieved without however necessarily increasing the depth of the installation as such.

What is more, the arrangement of the columns in the installation according to the invention advantageously enables not only those columns to be placed in parallel in topographical terms relative to each other but also the instrument members associated with each of those columns. In topographical terms, this arrangement is also particularly compact and reproducible. It is thus easy not only to have access thereto whether it be to make connections or to make modifications to the circuit (replacement of a column, of an instrument member, etc.).

This arrangement thus also makes it possible significantly to reduce the length of the disposable pipes of the treatment circuit and in particular of its supply line in particular so as to minimize the volume of liquid inside the installation circuit.

The arrangement of the pipes in the supply line linking the supply pump at least as far as the inlets to the chromatography columns promotes the equilibration between the different steps of treatment by chromatography and in particular the successive use of the different columns.

It therefore follows from the above that the installation for treatment of biological liquid according to the invention is particularly simple, convenient and economical.

It will be noted that the installation generally comprises at least two pumps.

Some of said instrument members associated with said chromatography columns are mounted on dedicated control and actuation platforms which are disposed in the same general transverse direction as said chromatography columns and which are substantially above said respective chromatography columns.

According to other preferred simple, convenient and economical features of the installation according to the invention:.

The disclosure of the invention will now be continued with the description of embodiments, given below by way of illustrative and non-limiting example, with reference to the accompanying drawings, in which:.

<FIG> illustrate an installation <NUM> for treatment by chromatography, in different assembly configurations.

The installation <NUM> here comprises a first cart <NUM>, a second cart <NUM> as well as a third cart <NUM>, which are configured to be juxtaposed and at least partially nested in each other.

In <FIG>, the first, second and third carts <NUM> to <NUM> are separated and at a distance from each other. The first and third carts <NUM> and <NUM> are arranged in the same longitudinal direction whereas the second cart <NUM> is located offset, in front of the third cart <NUM>.

In <FIG>, the first and third carts <NUM> and <NUM> are juxtaposed and nested along the longitudinal direction of extension of the installation <NUM>, whereas the second cart <NUM> is still located offset in front of the third cart <NUM>.

In <FIG>, the second cart <NUM> is partially nested in the third cart <NUM> and located in immediate proximity to the first cart <NUM> such that this second cart <NUM> is also partially nested with and juxtaposed against the first cart <NUM>.

A detailed description will now be given of the structure of each of the first, second and third carts <NUM> to <NUM> and of the components they carry, with reference to <FIG>, in which <FIG> are respectively a front view, a three-quarter view from the back, side views and a plan view of the installation <NUM> with its first, second and third carts <NUM> to <NUM> assembled, and in which <FIG> represent a control and actuation platform of the installation.

The first cart <NUM> is provided with a first metal chassis <NUM> having a first lower frame <NUM> here substantially rectangular, a first upper frame <NUM> here hexagonal, substantially L-shaped, and situated partially facing and at a distance from the first lower frame <NUM>, and several vertical uprights <NUM> connected to the first lower and upper frames <NUM> and <NUM> so as to form a rigid first chassis <NUM>.

The first lower frame <NUM> is mounted here on four castors to facilitate its transport.

Each of the first lower and upper frames <NUM> and <NUM> is formed of longitudinal bars, also called longerons, extending in a longitudinal direction, and transverse bars, also called cross-members, extending in a transverse direction, here substantially at a right angle to the longitudinal direction. The first lower frame <NUM> is furthermore formed from an intermediate cross-member <NUM> disposed between its two transverse bars and attached to its two longitudinal bars.

The first cart <NUM> carries a main electrical and pneumatic distribution cabinet <NUM> mounted on the first lower frame <NUM>, on the back <NUM> and on the first side <NUM> of the first cart <NUM>, a secondary cabinet <NUM> also mounted on the first lower frame <NUM>, but instead on the front <NUM> and on the first side <NUM> of the first cart <NUM>. The secondary cabinet <NUM> is thus disposed in front of the main cabinet <NUM>.

The main cabinet <NUM> extends generally vertically, which means that it is higher than it is long, from the first lower fame <NUM> and beyond the first upper frame <NUM>, whereas the secondary cabinet <NUM> extends generally longitudinally, which means that it is longer than it is high, between the first lower and upper frames <NUM> and <NUM>, from the transverse bar situated on the first side <NUM> of the first lower frame <NUM> to its intermediate cross-member <NUM>.

The first cart <NUM> furthermore carries a support plate <NUM> mounted on the first upper frame <NUM> and projecting from the latter over a second side <NUM> of the first cart <NUM>, which is an opposite side to its first side <NUM>; such that a portion of the support plate <NUM> overhangs beyond the first chassis <NUM>.

It will be noted that the support plate <NUM> here has a substantially L-shaped contour to conform to the contour of that first upper frame <NUM>, and is provided with a recess to enable the passage of the main cabinet <NUM>.

The support plate <NUM> is configured to receive reusable components of the treatment installation <NUM> and support means not only for these reusable components but also for the disposable components of that installation <NUM>.

In particular here, the installation <NUM> comprises a plurality of supply valves disposed on the first side <NUM> of the first cart <NUM> and partially housed in a lateral face of the main cabinet <NUM>, in two distinct rows.

The row situated furthest to the back <NUM> of the first cart <NUM> has five superposed three-way valves 18a to 18e and one two-way isolation valve <NUM> situated above the five three-way valves 18a to 18e; whereas the other row has two superposed three-way valves 20a and 20b and a two-way isolation valve <NUM> situated above the two three-way valves 20a and 20b (<FIG> and <FIG>). It will be noted that the isolation valves <NUM> and <NUM> are configured here to have either on/off operation, or proportional operation.

It will be noted that each of the valves <NUM> and <NUM> has a body housed in the main cabinet <NUM> and a head extending the body and projecting from the main cabinet <NUM> on the first side <NUM> of the first cart <NUM>.

Furthermore, each of the valves <NUM> to <NUM> is configured to be connected by disposable flexible pipes to containers having determined products.

In particular, the valves 20a to 20b are supply valves configured to be connected to containers of biological liquid to treat by chromatography and form the start of a supply line of a circuit for treatment by chromatography of the installation <NUM>.

For this, the valve 20a is here configured to be connected to a container of equilibration buffer product and to what is referred to as a reserve container of liquid to retreat, and the valve 20b is configured here to be connected to the valve 20a and to a container of biological liquid to treat.

As regards the valve <NUM> this is a proportional valve here configured to be connected to the valve 20b as well as to the rest of the supply line extending downstream of the valves 20a, 20b and <NUM>.

What is more, the valves 18a to 18e are inlet valves configured to be connected to containers of what are referred to as buffer products and to supply a treatment circuit of the installation for the purpose of preparing and/or cleaning and/or eluting and/or regenerating chromatography columns and form the start of an additional line of the circuit for treatment by chromatography of the installation <NUM>.

For this, the valve 18a is configured here to be connected to a container for equilibration buffer product and to a container for first washing buffer product, the valve 18b is configured here to be connected to the valve 18a and to a container of second washing buffer product, the valve 18c is configured here to be connected to the valve 18b and to a container for eluting buffer product, the valve 18d is configured here to be connected to the valve 18c and to a container for cleaning product, and the valve 18e is configured here to be connected to the valve 18d and to a container for regenerating buffer product.

As regards the isolation valve <NUM> this is a distribution valve here configured to be connected to the valve 18e as well as to the rest of the additional line extending downstream of the valves 18a to 18b and <NUM>.

The installation <NUM> comprises an air presence sensor <NUM> here fastened to a vertical upright <NUM> on the first side <NUM> of the first cart <NUM> and in immediate proximity to the supply valve 20a The air presence sensor <NUM> is configured here to be connected to a portion of pipe between the container for biological liquid and the supply valve 20b and makes it possible to detect the presence and/or the absence of product.

The installation <NUM> comprises a first flow meter <NUM> mounted via a fastening bracket <NUM> on a vertical upright <NUM> on the first side <NUM> of the first cart <NUM>. This first flow meter <NUM> is configured to be connected on the supply line, upstream, to the isolation valve <NUM>.

The installation <NUM> comprises a second flow meter <NUM> mounted via a fastening bracket <NUM> on the same vertical upright <NUM> on the first side <NUM> of the first cart <NUM>. This second flow meter <NUM> is configured to be connected on the additional line, upstream, to the isolation valve <NUM>.

The installation <NUM> comprises a main system for data processing <NUM> fastened to the main cabinet <NUM> and which is formed here by a computer provided with a keyboard and a monitor which are accessible from the front <NUM> of the first cart <NUM>, as well as a second data processing system <NUM> here formed by several actuation and control panels housed in the secondary cabinet and also accessible from the front <NUM> of the first cart <NUM>.

It will be noted that the main cabinet <NUM> is provided with actuation buttons <NUM> on a back face at the back <NUM> of the first cart <NUM> and with pneumatic and electrical connectors <NUM> provided on a lateral face of that cabinet <NUM>, which is an opposite face to the lateral face from which project the valves 18a to 18e, <NUM>, 20a, 20b and <NUM>.

The installation <NUM> comprises a first pump support <NUM> fastened on the front of the main cabinet <NUM> and on which is mounted a supply pump <NUM>, as well as a second pump support <NUM> also fastened on the front of the main cabinet <NUM> and on which is mounted an additional pump <NUM>.

The supply pump <NUM> is configured here to be connected on the supply line downstream of the supply valves 20a and 20b isolation valve <NUM> and is provided with a pump head disposed opposite the first flow meter <NUM> and connected to the latter; whereas the additional pump <NUM> is configured here to be connected on the additional line downstream of the inlet valves 18a to 18e and isolation valve <NUM> and is provided with a pump head disposed opposite the second flow meter <NUM> and connected to the latter. These pumps <NUM> and <NUM> are for example of diaphragm type and are configured to cause the products present in the containers connected to the valves 18a to 18e, 20a and 20b to flow according to the state of these latter.

The installation <NUM> comprises a first pressure sensor with a safety member <NUM> mounted, via a fastening bracket <NUM>, on the support plate <NUM>, on the first side <NUM> of the first cart <NUM>; as well as a second pressure sensor with a safety member <NUM> mounted, via a fastening bracket <NUM>, on the second pump support <NUM>.

The first pressure sensor with a safety member <NUM> is configured here to be connected on the supply line downstream of the supply pump <NUM>; whereas the second pressure sensor with a safety member <NUM> is configured here to be connected on the additional line downstream of the additional pump <NUM>.

The first and second pressure sensors with a safety member <NUM> and <NUM> are each configured to measure the pressure of the liquid flowing in the respective line of the treatment circuit and to stop the respective pump beyond a certain threshold pressure value.

The installation <NUM> comprises a first drain valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, on the side of the supply pump <NUM> towards the front <NUM> of the first cart <NUM>, and with a head extending the body and projecting from the support block. This first drain valve <NUM> is configured here to be connected on the supply line, upstream, to the supply pump <NUM> and, downstream, in particular to a waste container.

The installation <NUM> comprises a first debubbler valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, beside the first drain valve <NUM> towards the second side <NUM> of the first cart <NUM>, and with a head extending the body and projecting from the support block. This first debubbler valve <NUM> is configured here to be connected, on the supply line, upstream, to the first drain valve <NUM> and, downstream, in particular to a first debubbler <NUM> (see below).

The installation <NUM> comprises a second debubbler valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, beside the first debubbler valve <NUM> towards the second side <NUM> of the first cart <NUM>, and with a head extending the body and projecting from the support block. This second debubbler valve <NUM> is configured here to be connected, on the supply line, upstream, to the first debubbler valve <NUM> and to the first debubbler <NUM>.

This first debubbler <NUM> is mounted, via a fastening bracket <NUM>, on a vertical upright <NUM> of the first chassis <NUM>, on an opposite side of the main cabinet <NUM> to the supply and inlet valves, and rather on the second side <NUM> of the first cart. This first debubbler <NUM> is configured here to be connected, as inlet connection, to the first debubbler valve <NUM>, as main outlet connection, to the second debubbler valve <NUM> and, as secondary outlet connection, to a first venting valve <NUM>.

This first venting valve <NUM> is provided with a body housed in a support block <NUM> fastened to the fastening bracket <NUM>, and with a head extending the body and projecting from the support block. This first venting valve <NUM> is configured here to open to the atmosphere.

The installation <NUM> comprises a second drain <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, to the rear of the supply pump <NUM> and towards the second side <NUM> of the first cart <NUM>, and with a head extending the body and projecting from the support block. This second drain valve <NUM> is configured here to be connected on the additional line, upstream, to the additional pump <NUM> and, downstream, in particular to a waste container.

The installation <NUM> comprises a third debubbler valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, beside the second drain valve <NUM> towards the second side <NUM> of the first cart <NUM>, and with a head extending the body and projecting from the support block. This third debubbler valve <NUM> is configured here to be connected, on the additional line, upstream, to the second drain valve <NUM> and, downstream, in particular to a second debubbler <NUM> (see below).

The installation <NUM> comprises a fourth debubbler valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, beside the third debubbler valve <NUM> towards the second side <NUM> of the first cart <NUM>, and with a head extending the body and projecting from the support block. This fourth debubbler valve <NUM> is configured here to be connected, on the additional line, downstream, to the third debubbler valve <NUM> and to the second debubbler <NUM>.

This second debubbler <NUM> is mounted, via the fastening bracket <NUM>, on the vertical upright <NUM> of the first chassis <NUM>, on the opposite side of the main cabinet <NUM> to the supply and inlet valves, and rather on the second side <NUM> of the first cart. This second debubbler <NUM> is configured here to be connected, as inlet connection, to the third debubbler valve <NUM>, as main outlet connection, to the fourth debubbler valve <NUM> and, as secondary outlet connection, to a second venting valve <NUM>.

This second venting valve <NUM> is provided with a body housed in the support block <NUM> fastened to the fastening bracket <NUM>, and with a head extending the body and projecting from the support block. This second venting valve <NUM> is configured here to open to the atmosphere.

The installation <NUM> comprises a third drain valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, beside the second debubbler valve <NUM> towards the second side <NUM> of the first cart <NUM>, and with a head extending the body and projecting from the support block. This third drain valve <NUM> is configured here to be connected on the supply line, upstream, to the second debubbler valve <NUM> and, downstream, in particular to a waste container.

The installation <NUM> further comprises a fourth drain valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, beside the fourth debubbler valve <NUM> towards the back <NUM> of the first cart <NUM>, and with a head extending the body and projecting from the support block. This fourth drain valve <NUM> is configured here to be connected on the additional line, upstream, to the fourth debubbler valve <NUM> and, downstream, in particular to a waste container.

It will be noted that windows <NUM> are provided in the support plate <NUM> under the drain valves <NUM>, <NUM>, <NUM> and <NUM> to enable portions of pipe of the treatment circuit to be passed towards the waste containers which may be housed for example in a receiving space <NUM> provided between the first lower and upper frames <NUM> and <NUM> and between the secondary cabinet <NUM> and the second side <NUM> of the first chassis <NUM>.

The installation <NUM> comprises a third pressure sensor <NUM>, here without a safety feature, mounted via a fastening lug <NUM> here S-shaped on the support plate <NUM>, beside the third drain valve <NUM> towards the second side <NUM> of the first cart <NUM>. The third pressure sensor <NUM> is configured here to be connected to the supply line downstream of the third drain valve <NUM>.

The installation <NUM> comprises a first filter valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, beside the third pressure sensor <NUM> towards the second side <NUM> of the first cart <NUM>. The first filter valve <NUM> is configured here to be connected on the supply line, upstream, to the third pressure sensor <NUM> and, downstream, to a filter <NUM> (see below).

The installation <NUM> comprises a second filter valve <NUM> provided with a body housed in a support block <NUM> mounted on the support plate <NUM>, beside the first filter valve <NUM> towards the back <NUM> of the first cart <NUM>. The second filter valve <NUM> is configured here to be connected on the supply line, upstream, to the filter <NUM> and the first filter valve <NUM>.

This filter <NUM> is mounted, via a fastening bracket <NUM> mechanically connected to the top of the support blocks <NUM> and <NUM> respectively of the first and second filter valves <NUM> and <NUM>, substantially above these first and second filter valves <NUM> and <NUM>. This filter <NUM> is configured here to be connected, as inlet connection, to the first filter valve <NUM>, and as outlet connection, to the second filter valve <NUM>.

The installation <NUM> comprises a fourth pressure sensor <NUM>, here without safety feature, mounted via a fastening lug <NUM> here S-shaped on the support plate <NUM>, near the second filter valve <NUM> towards the back <NUM> of the first cart <NUM>; as well as a fifth pressure sensor <NUM> here without safety feature and which is mounted, via a fastening bracket <NUM> here S-shaped, on the support plate <NUM> near the fourth drain valve <NUM> and the fourth pressure sensor <NUM>, towards the back <NUM> of the first cart <NUM> (<FIG> and <FIG>).

The fourth pressure sensor <NUM> is configured here to be connected on the supply line, upstream, to the second filter valve <NUM>; whereas the fifth pressure sensor <NUM> is configured here to be connected on the additional line, upstream, to the fourth drain valve <NUM>.

The installation <NUM> further comprises a cable raceway formed by collars <NUM> to <NUM> provided for conveying electric and pneumatic cables (not shown) which run along a back edge of the support plate <NUM>, from the face of the main cabinet <NUM> where the connectors <NUM> are located towards the second side <NUM> of the first cart <NUM> and beyond to reach the overhanging portion of the support plate <NUM> (<FIG> and <FIG>). These cables enable the instrument members of the installation to be supplied.

It will be noted that the drain valves <NUM>, <NUM>, <NUM> and <NUM> are three-way valves with an inlet aperture and two outlet apertures, including the drain outlet aperture which is either open or closed whereas the inlet aperture and the other outlet aperture are always open; and the debubbler valves <NUM>, <NUM>, <NUM> and <NUM> and the filter valves <NUM> and <NUM> are three-way valves similar to the supply valves 20a and 20b and to the inlet valves 18a to 18e, of a type different from the drain valves (see below).

It will also be noted that the components described above in relation with the first cart <NUM> are located substantially within the occupied floor space defined by the first chassis <NUM>. In other words, with the exception of the collar <NUM>, these components are not disposed on the overhanging portion of the support plate <NUM>.

Furthermore, these components are diagrammatically illustrated in the first part of <FIG> (sheet <NUM>/<NUM> of the drawings) and mainly form instrument members (the valves and various sensors), among which are devices for measuring physico-chemical parameters (the various sensors) of the liquids passing in the treatment circuit, in the supply and additional lines.

The installation <NUM> further comprises three dedicated control and actuation platforms 80a, 80b and 80c, mounted on the overhanging portion of the support plate <NUM>, which each extend in the vertical direction relative to the generally longitudinal direction of extension of the first cart <NUM>, and which are disposed on the support plate <NUM> in a generally transverse direction to the generally longitudinal direction of extension of the first cart <NUM>.

In particular, the three platforms 80a, 80b and 80c are arranged substantially in a triangle, around a cut-out <NUM> formed at one end of the portion of the support plate <NUM> which overhangs.

As the platforms 80a, 80b and 80c are identical, only one will be described in detail, which is platform 80a, knowing that this description applies to each of the other platforms 80b and 80c, in particular with reference to <FIG>.

Platform 80a comprises instrument members, including three distribution valves 81a, 82a and 83a, each provided with a body and a head extending the body, and several measuring devices including a conductivity sensor 78a, a pH sensor 85a and an air presence sensor 86a.

Platform 80a comprises a support block 84a here of substantially parallelepiped shape, which extends vertically, and in which are housed the body of the valves 81a, 82a and 83a and from which the heads of the valves 81a, 82a and 83a project laterally.

In particular, the heads of the valves 81a and 82a project from a first lateral face 87a of the support block 84a here turned towards the first side <NUM> of the first cart <NUM>, whereas the head of the valve 83a projects from a second lateral face 88a of the support block 84a turned towards the second side <NUM> of the first cart <NUM>.

Platform 80a further comprises a support plate 89a fastened to a third lateral face 90a of the support block 84a, turned towards the back <NUM> of the first cart <NUM>, and having an arm 191a which projects from the support block 84a and on which are mounted the sensors of conductivity 78a, pH 85a and air presence 86a.

In particular, the air presence sensor 86a is directly mechanically connected to a free end of the arm 191a whereas the sensors of conductivity 78a and pH 85a are mounted with partial insertion in a fluid chamber <NUM>, which chamber is fastened on a flange <NUM> itself mechanically connected to the arm 191a, between its free end where the air presence sensor 86a is fastened and the portion of the support plate 89a fastened on the third lateral face 90a of the support block 84a.

This fluid chamber <NUM> here forms an integral part of the supply line of the treatment circuit and has two chamber connectors which are for example male for the connection of portions of pipes, one of the chamber connectors being directed towards the support block 84a and the other of the chamber connectors being directed towards the air presence sensor 86a.

Valve 83a, valve 81a, valve 82a, the conductivity sensor 78a, the air presence sensor 86a and the pH sensor 85a are disposed substantially above each other on the dedicated control and actuation platform 80a.

Each of the valves 81a, 81b and 81c is configured here to be connected, on the supply line, upstream, to the fourth pressure sensor <NUM> and, downstream, to the respective valve 82a, 82b and 82c.

Each of the valves 81a, 81b and 81c is furthermore configured here also to be connected, on the additional line, upstream, to the fifth pressure sensor <NUM> and, downstream, to the respective valve 82a, 82b and 82c.

Each valve 82a, 82b and 82c is configured here to be connected, on the supply line, upstream, to the respective valve 81a, 81b and 81c, and, downstream, at the same time to the respective pH sensor 85a, 85b and 85c and to the respective conductivity sensor 78a, 78b and 78c.

Each of the pH sensors 85a, 85b and 85c and conductivity sensors 78a, 78b and 78c is thus configured here to be connected on the supply line, upstream, to the respective valve 82a, 82b and 82c and, downstream, to the respective air presence sensor 86a, 86b and 86c.

Each air presence sensor 86a, 86b and 86c is configured here to be connected, upstream, at the same time to the respective pH sensor 85a, 85b and 85c and to the respective conductivity sensor 78a, 78b and 78c and, downstream, to the respective valve 83a, 83b and 83c.

Each of the valves 83a, 83b and 83c is configured here to be connected, on the supply line, upstream, to the respective air presence sensor 86a, 86b and 86c and, downstream, in particular to a respective waste container and to a respective chromatography column (see below).

It will be noted that the distribution valves 81a-c, 82a-c and 83a-c are similar valves here to the filter valves <NUM> and <NUM>, to the supply valves 20a and 20b and to the inlet valves 18a to 18e.

As explained above, all these valves are provided with a valve body and with a valve head which extends from the body, which valve head is provided here to receive portions of pipes of the respective line (supply or additional) where the respective valve is located.

In particular, with reference to <FIG>, valve 81a is a three-way valve, of which two ways are inlets and one an outlet or one an inlet and two outlets, provided with two channels <NUM> and <NUM> open at their ends, formed in the head, and configured to receive portions of pipes, and here a pinch mechanism configured to allow or prevent the passage of liquid in the portions of pipes received in the two channels <NUM> and <NUM>, by pinching one or other of these latter. This pinching mechanism is housed in the head, between the two channels <NUM> and <NUM>, and is actuated by a pneumatic actuator housed in the valve body. These are multi-tube pinch valves.

The other valves 81b-c, 82a-c, 83a-c, 18a-e, 20a-b, <NUM> and <NUM> here have a similar structure to that of valve 81a.

As a variant, the aforementioned three-way valves could be of a type other than that of the so-called pinch valves.

The second cart <NUM> is provided with a second metal chassis <NUM> having a second lower frame <NUM> here substantially rectangular, mounted on castors <NUM>, a support board placed on that lower frame <NUM> and a maneuvering handle of inverted U-shape, which projects from the second lower frame <NUM>, and which is provided to guide the transportation of the second cart <NUM>.

It will be noted that the second lower frame <NUM> is formed from two longitudinal bars, also called longerons, extending in a longitudinal direction, and from two transverse bars, also called cross-members, extending in a transverse direction, here substantially at a right angle to the longitudinal direction. Here, the cross-members and longerons of the second lower frame <NUM> have substantially the same dimensions.

The installation <NUM> comprises several chromatography columns 99a-c, here three in number, which are placed on the support board in an arrangement, here triangular, enabling these columns to extend in a generally transverse direction to the generally longitudinal direction of extension of the installation. In other words, the three columns 99a, 99b and 99c extend within the length of cross-members rather than within the length of the longerons of the second lower frame <NUM>.

These columns 99a-c are each provided, on an upper face, with an inlet connector 100a-c and with an outlet connector associated with a manual valve 101a-c.

These columns 99a, 99b and 99c are configured here to be connected, on the supply line, upstream, respectively to the distribution valves 83a, 83b and 83c at the location of their respective inlet connector 100a-c.

As regards the third cart <NUM>, this is provided with a third metal chassis <NUM>, of substantially inverted U-shape, having a third lower frame <NUM> of which a first part <NUM> is substantially C-shaped here and open to the front <NUM> of the third cart <NUM>, and a second part <NUM> here substantially rectangular and juxtaposed against the first part <NUM> on a first free side <NUM> (or end) of the third cart <NUM>.

The third cart <NUM> is furthermore provided with vertical uprights <NUM> connected to the third lower frame <NUM> and linked to each other, on the top of the third chassis <NUM>, via two longitudinal bars, or longerons, extending in a longitudinal direction, and via two transverse bars, or cross-members, extending in a transverse direction, here substantially orthogonal to the longitudinal direction.

The third lower frame <NUM> too is mounted on four castors <NUM> to facilitate its transport.

The inverted U-shape of the third chassis <NUM> is provided to form a receiving space <NUM> so as to receive the second cart <NUM> (see below).

The installation <NUM> comprises additional instrument supports 111a-c, here three in number, disposed downstream of the columns 99a-c and each being dedicated to a chromatography column.

These additional instrument supports 111a, 111b and 111c are mounted on the third cart <NUM>, via respective fastening brackets 112a, 112b and 112c which are fastened, directly or indirectly, to a transverse bar of the third chassis <NUM>, on the first free side <NUM> of the third cart <NUM>.

In particular, here, the fastening brackets 112a and 112c are bent and directly mechanically connected to the third chassis <NUM>, whereas the fastening bracket 112b is mechanically connected to an intermediate tube (not shown) itself fastened directly to dedicated lugs of the brackets 112a and 112c.

Thus, the additional instrument supports 111a, 111b and 111c are disposed on the third cart <NUM> in a triangular general arrangement and along the transverse direction.

The installation <NUM> comprises several additional measuring devices carried by each of these additional instrument supports 111a, 111b and 111c, among which are respectively conductivity sensors 113a, 113b and 113c, pH sensors 114a, 114b and 114c and UV radiation sensors 115a, 115b and 115c, each being mounted, by group of three distinct sensors, on a respective fastening bracket 112a, 112b and 112c.

In particular, each of these sensors 113a-c, 114a-c and 115a-c is mounted with partial insertion in a fluid chamber 195a, 195b and 195c, substantially similar to that described above, which is fastened to a flange here centrally holed (not shown) which is itself mechanically connected to the respective bracket.

The conductivity sensors 113a-c and the pH sensors 114a-c are arranged in rather similar manner to those described above concerning platforms 80a-c, that is to say substantially vertically and respectively one opposite the other.

As regards the UV radiation sensors 115a-c, these are arranged substantially perpendicularly to the conductivity sensors 113a-c and to the pH sensors 114a-c on each respective additional instrument support 111a-c, on opposite sides of the fluid chamber and the holed flange, which is holed so as to enable the light rays to pass from an emitter to a receiver while passing through the fluid chamber, and thereby enable the measurement of the UV radiation.

The fluid chamber on each additional instrument support here forms an integral part of the supply line of the treatment circuit and has two chamber connectors for example male for the connection of portions of pipes.

Each of the conductivity sensors 113a-c, pH sensors 114a-c and UV radiation sensors 115a-c is configured here to be connected on the supply line, upstream, to the outlet connector associated with the respective manual valve 101a, 101b and 101c.

The installation <NUM> further comprises a plurality of supplementary instrument members, among which are pressure sensors 116a, 116b and 116c, here without safety feature, and optionally spectrophotometers 117a, 117b and 117c.

The spectrophotometers 117a, 117b and 117c are placed on a shelf <NUM> which is mounted in a raised location relative to the third chassis <NUM> and is mechanically connected to the longitudinal bars of that third chassis <NUM>, which are situated on the front <NUM> and on the back <NUM> of the third cart <NUM>.

The pressure sensors 116a, 116b and 116c are mounted on that shelf <NUM>, via respective fastening lugs 119a, 119b and 119c which are directly mechanically fastened to that shelf <NUM>.

The shelf <NUM> extends generally in the transverse direction and the spectrophotometers 117a-c and pressure sensors 116a-c are thus disposed along that same transverse direction.

Each pressure sensor 116a, 116b and 116c is configured to be connected, upstream, to the fluid chamber of a respective additional instrument support 111a-c to be connected both to a respective conductivity sensor 113a-c, to a respective pH sensor 114a-c and to a respective UV radiation sensor 115a-c.

Each spectrophotometer 117a, 117b and 117c is configured here to be connected on the supply line, upstream, to a respective pressure sensor 116a, 116b and 116c.

The installation <NUM> further comprises continuity valves 121a, 121b and 121c, reserve valves 122a, 122b and 122c, and outlet valves 123a, 123b and 123c, which are mounted on a support block <NUM> of cabinet form, disposed on the second part <NUM> of the third lower frame <NUM> of the third chassis <NUM>. It will be noted that the continuity valves 121a, 121b and 121c and the reserve valves 122a, 122b and 122c may also be called outlet valves since they are located downstream of the columns.

The continuity valves 121a are mounted on an upper face of the support block <NUM> whereas the reserve valves 122a, 122b and 122c and outlet valves 123a, 123b and 123c are mounted on a lateral face of the support block <NUM> on the first free side <NUM> of the third cart <NUM>.

These continuity 121a-c, reserve 122a-c and outlet 123a-c valves are all similar here to the distribution valves 81a-c, 82a-c and 83a-c, to the filter valves <NUM> and <NUM>, to the supply valves 20a and 20b and to the inlet valves 18a to 18e.

In particular, the continuity 121a-c, reserve 122a-c and outlet 123a-c valves are each provided with a body housed in the support block <NUM> and with a head extending the body and which projects from the respective upper or lateral face of the support block <NUM>.

What is more, these continuity 121a-c, reserve 122a-c and outlet 123a-c valves are multitube pinch valves like those described earlier.

The continuity valve 121a is configured here to be connected on the supply line, downstream, to the spectrophotometer 117a and, upstream, in particular to the distribution valve 82c connected to the column 99c so as to create a fluid loop from the column 99a to the column 99c.

The continuity valve 121b is configured here to be connected on the supply line, downstream, to the spectrophotometer 117b and, upstream, in particular to the distribution valve 82a connected to the column 99a so as to create a fluid loop from the column 99b to the column 99a.

The continuity valve 121c is configured here to be connected on the supply line, downstream, to the spectrophotometer 117c and, upstream, in particular to the distribution valve 82b connected to the column 99b so as to create a fluid loop from the column 99a to the column 99b.

Each of the reserve valves 122a, 122b and 122c is configured here to be connected, upstream, on the supply line to the respective continuity valve 121a, 121b and 121c and, downstream, in particular on a reserve line to the reserve container, itself configured to be connected to the supply valve 20a.

Each of the outlet valves 123a, 123b and 123c is configured here to be connected, on the supply line, upstream, to the respective reserve valve 122a, 122b and 122c and, downstream, to what is referred to as a fraction container and to a waste container, according to the state of the respective valve.

With reference to <FIG>, the third cart <NUM> is moved towards the first cart <NUM> until it is juxtaposed against it, by a second side <NUM> of the third cart <NUM>, which is an opposite side to its free first side <NUM>, with the second side <NUM> of the first cart <NUM>.

In this configuration, the first chassis <NUM> of the first cart <NUM> and the third chassis <NUM> of the third cart <NUM> are in abutment against each other, with the top of the third chassis <NUM>, formed by the two longitudinal bars, being partially nested under the portion of the support plate <NUM> of the first cart <NUM> which projects from the first chassis <NUM>.

It will be noted that the first and third carts <NUM> and <NUM> have the same depth, in the transverse direction, and that the arrangement of one relative to the other is made such that the receiving space <NUM> formed in the third chassis <NUM> remains accessible equally by the front <NUM> and by the top of the third cart <NUM>, in particular via the cut-out <NUM> formed in the portion of the support plate <NUM> which projects from the first chassis <NUM>.

With reference now to <FIG>, the second cart <NUM>, already prepared with the three columns 99a-c, is moved towards the assembly formed by the first and third carts <NUM> and <NUM> then inserted by the front <NUM> into the receiving space <NUM> formed in the third chassis <NUM> of the third cart <NUM>.

In this configuration, the second chassis <NUM> of the second cart <NUM> is substantially sandwiched in the third lower frame <NUM> of the third chassis <NUM> of the third cart <NUM>, and the columns 99a-c are disposed substantially beneath the control and actuation platforms 80a-c and the additional instrument supports 111a-c and are accessible from the top of the installation <NUM>, and in particular from the cut-out <NUM> and part of the opening formed on the top of the third chassis <NUM>, between the two transverse bars and the longitudinal bar which is located towards the first free side <NUM> of the third cart <NUM>.

It will be noted that the second cart <NUM> has a depth which enables it not to go beyond the floor space occupied on the ground, in depth, taken by the first and third carts <NUM> and <NUM>, except at the front <NUM> towards the front <NUM> of the third cart <NUM> where the maneuvering handle <NUM> remains accessible.

It will also be noted that in this configuration, a control and actuation platform 80a-c and an additional instrument support 111a-c are dedicated to a respective column 99a-c.

The arrangement of the first, second and third carts <NUM> to <NUM> and of the components which they comprise makes it possible to provide a particularly compact, flexible and intuitive topography of the treatment circuit and of these components that make it up.

In particular, it is particularly visible that the supply line and the additional line extend longitudinally, substantially in parallel, from the supply valves 20a-b and the inlet valves 18a-e, to the dedicated control and actuation platforms 80a-c.

It is also particularly visible that the supply line then continues along three branches of the treatment circuit which extend over a short longitudinal distance but which pass, substantially in parallel, from the dedicated control and actuation platforms 80a-c to the additional instrument supports 111a-c, passing via the columns 99a-c, and more generally to the outlet valves 123a-c.

This makes it possible in particular to give a shorter length for all the carts <NUM> to <NUM>, while limiting their depth, on account of the triangular disposition of the three columns 99a-c, but also of the platforms 80a-c and also of the additional instrument supports 111a-c.

This also makes it possible to provide a treatment circuit with shorter lengths of pipes and substantially similar lengths, over the first part of the circuit from the supply valves 20a-b and the inlet valves 18a-e to the dedicated control and actuation platforms 80a-c, and/or over the second part of the circuit from the dedicated control and actuation platforms 80a-c to the columns 99a-c, and/or over the third part of the circuit from the columns 99a-c to the outlet valves 123a-c; so as to ensure continuity of treatment, as explained later.

A description will now be made of the treatment circuit and of a method of treatment by chromatography using the treatment circuit provided by the installation and illustrated diagrammatically in <FIG> and <FIG>.

In these drawings, references <NUM>, <NUM> and <NUM> are respectively given to the supply line, the additional line and to the reserve line of the circuit.

It will be noted that the term "pipe" may be comprised in the present document as a portion of piping, preferably flexible and disposable, linking components of the circuit, it being possible for this portion equally well to comprise a single duct or on the contrary several ducts possibly having different diameters.

The biological liquid to treat is initially located in what is referred to as a source container or in a source bag <NUM> filled with liquid coming from a bioreactor or coming from a later treatment. This source bag <NUM> is connected via a connector to a first pipe <NUM> which is connected to the supply valve 20b on the supply line <NUM>. The air presence sensor <NUM> is also connected on this first pipe <NUM>, between the bag <NUM> and the valve 20b.

The biological liquid to treat may also be located in a reserve container <NUM> filled with liquid coming from a step of treatment by chromatography (see below). This reserve container <NUM> is connected via a connector to a second pipe <NUM> which is connected to the supply valve 20a on the supply line <NUM>.

A first equilibration buffer product is initially located in a first equilibration container <NUM> which is connected via a connector to a main pipe <NUM> of the supply line <NUM>, which main pipe <NUM> is connected to the supply valve 20a and passes from that first equilibration container <NUM> to a first branching connector <NUM>, or distributor, of the installation <NUM> (see below), where that main pipe <NUM> subdivides into three branches 135a, 135b and 135c.

A second equilibration buffer product is initially located in a second equilibration container <NUM> which is connected via a connector to an additional pipe <NUM> of the additional line <NUM>, which additional pipe <NUM> is connected to the inlet valve 18a and passes from that second equilibration container <NUM> to a second branching connector <NUM>, or distributor, of the installation <NUM> (see below), where that additional pipe <NUM> subdivides into three branches 143a, 143b and 143c.

A first washing product is initially located in a first washing container <NUM> which is connected via a connector to a third pipe <NUM> which is connected to the inlet valve 18a on the additional line <NUM>.

A second washing product is initially located in a second washing container <NUM> which is connected via a connector to a fourth pipe <NUM> which is connected to the inlet valve 18b on the additional line <NUM>.

An elution product is initially located in an elution container <NUM> which is connected via a connector to a fifth pipe <NUM> which is connected to the inlet valve 18c on the additional line <NUM>.

A cleaning product is initially located in a cleaning container <NUM> which is connected via a connector to a sixth pipe <NUM> which is connected to the inlet valve 18d on the additional line <NUM>.

A regeneration product is initially located in a regeneration container <NUM> which is connected via a connector to a seventh pipe <NUM> which is connected to the inlet valve 18e on the additional line <NUM>.

As indicated above, it is to be recalled that the two-way valve <NUM>, the flowmeter <NUM>, the supply pump <NUM>, the pressure sensor with safety feature <NUM>, the first drain valve <NUM>, the first and second debubbler valves <NUM> and <NUM>, the third drain valve <NUM>, the first and second filter valves <NUM> and <NUM>, and the fourth pressure sensor <NUM> are successively installed on the main pipe <NUM> of the supply line <NUM>, from the supply valve 20b to the first branching connector <NUM>.

The first drain valve <NUM> is connected here to an eighth pipe <NUM> to which is connected, via a connector, a waste container <NUM>.

The first debubbler valve <NUM> is connected here to a ninth pipe <NUM> to which is connected, via a connector, the inlet of the first debubbler <NUM>, and the second debubbler valve <NUM> is connected here to a tenth pipe <NUM> to which is connected, via a connector, the main outlet of the first debubbler <NUM>.

The third drain valve <NUM> is connected here to an eleventh pipe <NUM> to which is connected, via a connector, a waste container <NUM>.

The first filter valve <NUM> is connected here to a twelfth pipe <NUM> to which is connected, via a connector, the inlet of the filter <NUM>, and the second filter valve <NUM> is connected here to a thirteenth pipe <NUM> to which is connected, via a connector, the outlet of the filter <NUM>.

As indicated above, it is to be recalled that the two-way valve <NUM>, the flowmeter <NUM>, the additional pump <NUM>, the pressure sensor with safety feature <NUM>, the second drain valve <NUM>, the third and fourth debubbler valves <NUM> and <NUM>, the fourth drain valve <NUM>, and the fifth pressure sensor <NUM> are successively installed on the additional pipe <NUM> of the additional line <NUM> from the inlet valve 18e to the second branching connector <NUM>.

The second drain valve <NUM> is connected here to a fourteenth pipe <NUM> to which is connected, via a connector, a waste container <NUM>.

The third debubbler valve <NUM> is connected here to a fifteenth pipe <NUM> to which is connected, via a connector, the inlet of the second debubbler <NUM>, and the fourth debubbler valve <NUM> is connected here to a sixteenth pipe <NUM> to which is connected, via a connector, the main outlet of the second debubbler <NUM>.

The fourth drain valve <NUM> is connected here to a seventeenth pipe <NUM> to which is connected, via a connector, a waste container <NUM>.

What is more, the distribution valves 81a and 82a, the conductivity 78a, pH 85a and air presence 86a sensors, via the dedicated control and actuation platform 80a the distribution valve 83a the chromatography column 99a and a manual valve 190a associated with the column 99a at the outlet of the latter, the conductivity 113a, pH 114a and UV radiation 115a sensors, via the dedicated additional instrument support 111a, the pressure sensor 116a, the spectrophotometer 117a and the continuity 121a, reserve 122a and outlet 123a valves are successively installed on the branch 135a of the main pipe <NUM> on the supply line <NUM>, from the first branching connector <NUM>.

The distribution valve 81a is connected here, upstream, to the first branching connector <NUM> and, downstream, to the branch 143a of the additional pipe <NUM>.

The distribution valve 82a is connected here, upstream, to the distribution valve 81a and, downstream, to a first continuity pipe <NUM> and to the instrument members of the platform 80a.

The distribution valve 83a is connected here, downstream, to the instrument members of the platform 80a and, upstream, to an eighteenth pipe <NUM> to which is connected, via a connector, a waste container <NUM>, and to the instrument members of the additional support 111a.

The continuity valve 121a is connected here, upstream, to the spectrophotometer 117a and, downstream, to a second continuity pipe <NUM> and to the reserve valve 122a.

The reserve valve 122a is connected here, upstream, to the continuity valve 121a and, downstream, to a reserve pipe <NUM> and to the outlet valve 123a. This reserve pipe <NUM> is connected here, via a connector, to the reserve container <NUM>.

The outlet valve 123a is connected here, upstream, to the reserve valve 122a and, downstream, to a nineteenth pipe <NUM> to which is connected, via a connector, a fraction container <NUM>, and to a waste container <NUM> via another connector connected to the branch 135a of the main pipe <NUM>.

The distribution valves 81b and 82b, the conductivity 78b, pH 85b and air presence 86b sensors, via the dedicated control and actuation platform 80b, the distribution valve 83b, the chromatography column 99b and a manual valve 190b associated with the column 99b at the outlet of the latter, the conductivity 113b, pH 114b and UV radiation 115b sensors, via the dedicated additional instrument support 111b, the pressure sensor 116b, the spectrophotometer 117b, and the continuity 121b, reserve 122b and outlet 123b valves are successively installed on the arm 135b of the main pipe <NUM> on the supply line <NUM>, from the first branching connector <NUM>.

The distribution valve 81b is connected here, upstream, to the first branching connector <NUM> and, downstream, to the branch 143b of the additional pipe <NUM>.

The distribution valve 82b is connected here, upstream, to the distribution valve 81b and, downstream, to a third continuity pipe <NUM> and to the instrument members of the platform 80b.

The distribution valve 83b is connected here, downstream, to the instrument members of the platform 80b and, upstream, to a twenty-first pipe <NUM> to which is connected, via a connector, a waste container <NUM>, and to the instrument members of the additional support 111b.

The continuity valve 121b is connected here, upstream, to the spectrophotometer 117b and, downstream, to the first continuity pipe <NUM> and to the reserve valve 122b.

The reserve valve 122b is connected here, upstream, to the continuity valve 121b and, downstream, to a first annex reserve pipe <NUM> and to the outlet valve 123b. This first annex reserve pipe <NUM> is linked to the reserve pipe <NUM>.

The outlet valve 123b is connected here, upstream, to the reserve valve 122b and, downstream, to a first annex fraction pipe <NUM> which is linked to the fraction pipe <NUM>, and to a waste container <NUM> via a connector connected on the branch 135b of the main pipe <NUM>.

What is more, the distribution valves 81c and 82c the conductivity 78c, pH 85c and air presence 86c sensors, via the dedicated control and actuation platform 80c, the distribution valve 83c, the chromatography column 99c and a manual valve 190c associated with the column 99c at the outlet of the latter, the conductivity 113c, pH 114c and UV radiation 115c sensors, via the dedicated additional instrument support 111c, the pressure sensor 116c, the spectrophotometer 117c, and the continuity 121c, reserve 122c and outlet 123c valves are successively installed on the arm 135c of the main pipe <NUM> on the supply line <NUM>, from the first branching connector <NUM>.

The distribution valve 81c is connected here, upstream, to the first branching connector <NUM> and, downstream, to the branch 143c of the additional pipe <NUM>.

The distribution valve 82c is connected here, upstream, to the distribution valve 81c and, downstream, to a second continuity pipe <NUM> and to the instrument members of the platform 80c.

The distribution valve 83c is connected here, downstream, to the instrument members of the platform 80c and, upstream, to a twenty-second pipe <NUM> to which is connected, via a connector, a waste container <NUM>, and to the instrument members of the additional support 111c.

The continuity valve 121c is connected here, upstream, to the spectrophotometer 117c and, downstream, to the third continuity pipe <NUM> and to the reserve valve 122c.

The reserve valve 122c is connected here, upstream, to the continuity valve 121c and, downstream, to a second annex reserve pipe <NUM> and to the outlet valve 123c. This second annex reserve pipe <NUM> is linked to the reserve pipe <NUM> via the first annex reserve pipe <NUM>.

The outlet valve 123c is connected here, upstream, to the reserve valve 122c and, downstream, to a second annex fraction pipe <NUM> which is linked to the fraction pipe <NUM> via the first annexfraction pipe <NUM>, and to a waste container <NUM> via a connector connected to the branch 135c of the main pipe <NUM>.

The treatment by chromatography using the circuit described above may comprise the following steps.

A step of preparing the circuit is implemented, with a first filling phase.

For this, the first and second equilibration containers <NUM> and <NUM> are connected to the main and additional pipes <NUM> and <NUM>. The valves 18a-e, <NUM>, 20a-b, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, 81a-c, 82a-c and 83a-c, the pumps <NUM> and <NUM>, and the branching connectors <NUM> and <NUM> are controlled to make the equilibration liquid flow in parallel in the main <NUM> and additional <NUM> pipes, passing via the first and second debubblers <NUM> and <NUM> and by the filter <NUM> but shunting the waste containers <NUM>, <NUM>, <NUM> and <NUM>, to reach the valves 83a-c which direct the liquid into the waste containers <NUM>, <NUM> and <NUM>, ahead of the columns 99a-c.

A second filling phase is implemented. For this, only the second equilibration container <NUM> is connected. The valves 18a-e, <NUM>, <NUM>, <NUM>, <NUM>, 81c, 82a-c, 83a-c and 121a-c, the additional pump <NUM>, and the second branching connector <NUM> are controlled to make the equilibration liquid flow, successively, in the additional pipe <NUM>, shunting the second debubbler <NUM> and the waste containers <NUM> and <NUM>, in the branch 135c of the main pipe <NUM>, through the column 99c (shunting the waste container <NUM>) and in the third continuity pipe <NUM> to reach the valve 83b which directs the liquid into the waste container <NUM> ahead of the column 99b.

When the air presence sensor 86c no longer detects air, the valve 83b is controlled to shunt the waste container <NUM> and in order for the liquid to be conveyed beyond the preceding path, through the column 99b and into the first continuity pipe <NUM> to reach the valve 83a which directs the liquid into the waste container <NUM> ahead of the column 99a.

When the air presence sensor 86a no longer detects air, the valve 83a is controlled to shunt the waste container <NUM> and in order for the liquid to be conveyed beyond the previous path, through the column 99a and into the second continuity pipe <NUM>.

It will be noted that the two filling phases may be implemented with a product other than the equilibration buffer product.

An equilibration phase successively to each of the columns 99a-c is next implemented.

For this, only the second equilibration container <NUM> is connected. The valves 18a-e, <NUM>, <NUM>, <NUM>, <NUM>, 81c, 82c, 83c, 121c, 122c and 123c, the additional pump <NUM>, and the second branching connector <NUM> are controlled to make the equilibration liquid pass in the additional pipe <NUM>, shunting the second debubbler <NUM> and the waste containers <NUM> and <NUM>, in the branch 135c of the main pipe <NUM>, through the column 99c (shunting the waste container <NUM>) to reach the valve 123c which directs the liquid into the waste container <NUM>; until the values of pH and conductivity measured by the sensors 113c and 114c after the column 99c are identical to the values of pH and conductivity measured by the sensors 78c and 85c, ahead of the column 99c.

Next, the second equilibration container <NUM> is connected, the valves 18a-e, <NUM>, <NUM>, <NUM>, <NUM>, 81b, 82b, 83b, 121b, 122b and 123b, the additional pump <NUM>, and the second branching connector <NUM> are controlled to make the equilibration liquid pass in the additional pipe <NUM>, shunting the second debubbler <NUM> and the waste containers <NUM> and <NUM>, in the branch 135b of the main pipe <NUM>, through the column 99b (shunting the waste container <NUM>) to reach the valve 123b which directs the liquid into the waste container <NUM>; until the values of pH and of conductivity measured by the sensors 113b and 114b after the column 99b are identical of the values of pH and of conductivity measured by the sensors 78b and 85b, ahead of the column 99b.

Next, the second equilibration container <NUM> is connected, the valves 18a-e, <NUM>, <NUM>, <NUM>, <NUM>, 81a, 82a, 83a, 121a, 122a and 123a, the additional pump <NUM>, and the second branching connector <NUM> are controlled to make the equilibration liquid pass in the additional pipe <NUM>, shunting the second debubbler <NUM> and the waste containers <NUM> and <NUM>, in the branch 135a of the main pipe <NUM>, through the column 99a (shunting the waste container <NUM>) to reach the valve 123a which directs the liquid into the waste container <NUM>; until the values of pH and of conductivity measured by the sensors 113a and 114a after the column 99a are identical of the values of pH and of conductivity measured by the sensors 78a and 85a, ahead of the column 99a.

A first loading phase can be carried out. For this, the product container <NUM> (or flexible bag) is connected to the first pipe <NUM>. The valves 20b, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, 81c, 82c, 83c, 121c, 82b, 83b, 121b, 122b and 123b, the first branching connector <NUM> and the supply pump <NUM> are controlled to cause to flow the biological liquid to treat, successively, in the main pipe <NUM> passing via the first debubbler <NUM>, by the filter <NUM>, shunting the waste containers <NUM> and <NUM>, then in the branch 135c shunting the waste container <NUM> and passing through the column 99c, then into the third continuity pipe <NUM>, then into the branch 135b, shunting the waste container <NUM>, passing through the column 99b, shunting the reserve <NUM> and fraction 167containers, to reach the valve 123b which directs the treated liquid into the waste container <NUM>.

A new loading phase may be carried out, in particular when the column 99c is what is referred to as loaded. For this, the product container <NUM> (or flexible bag) is still connected to the first pipe <NUM>. The valves 20b, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, 81b, 82b, 83b, 121b, 82a, 83a, 121a, 122a and 123a, the first branching connector <NUM> and the supply pump <NUM> are controlled to cause to flow the biological liquid to treat, successively, in the main pipe <NUM> passing via the first debubbler <NUM>, by the filter <NUM>, shunting the waste containers <NUM> and <NUM>, then in the branch 135b shunting the waste container <NUM> and passing through the column 99c then into the first continuity pipe <NUM>, then into the branch 135a, shunting the waste container <NUM>, passing through the column 99a, shunting the reserve <NUM> and fraction <NUM> containers, to reach the valve 123a which directs the treated liquid into the waste container <NUM>.

In parallel with this new loading phase, a phase of recovery and preparation of the column 99c may be carried out. For this, the first and second washing containers <NUM> and <NUM>, the elution container <NUM>, the cleaning container <NUM> and the regeneration container <NUM> are connected to the respective pipes <NUM> to <NUM>. The valves 18a-e, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, 81c, 82c, 83c, 121c, 122c and 123c, the second branching connector <NUM> and the additional pump <NUM> are controlled to make flow:.

A new loading phase may be carried out, in particular when the column 99b is said to be loaded. For this, the product container <NUM> (or flexible bag) is still connected to the first pipe <NUM>. The valves 20b, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, 81a, 82a, 83a, 121a, 82c, 83c, 121c, 122c and 123c, the first branching connector <NUM> and the supply pump <NUM> are controlled to cause to flow the biological liquid to treat, successively, in the main pipe <NUM> passing via the first debubbler <NUM>, by the filter <NUM>, shunting the waste containers <NUM> and <NUM>, then in the branch 135a, shunting the waste container <NUM> and passing through the column 99a, then into the second continuity pipe <NUM>, then into the branch 135c, shunting the waste container <NUM>, passing through the column 99c, shunting the reserve <NUM> and fraction <NUM> containers, to reach the valve 123c which directs the treated liquid into the waste container <NUM>.

In parallel with this new loading phase, a phase of recovery and preparation of the column 99b may be carried out. For this, the first and second washing containers <NUM> and <NUM>, the elution container <NUM>, the cleaning container <NUM> and the regeneration container <NUM> are connected to the respective pipes <NUM> to <NUM>. The valves 18a-e, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, 81b, 82b, 83b, 121b, 122b and 123b, the second branching connector <NUM> and the additional pump <NUM> are controlled to make flow:.

A new loading phase may be carried out, in particular when the column 99a is said to be loaded. This new loading phase is identical to the previous phase referred to as first loading, with the biological liquid passing through the columns 99c then 99b. Alternatively, this new loading phase may be carried out by virtue of the connection of the reserve container <NUM> to the supply valve 20a rather than the connection of the product container <NUM>, so as to treat the recovered first cleaning product.

In parallel with this new loading phase, a phase of recovery and preparation of the column 99a may be carried out. For this, the first and second washing containers <NUM> and <NUM>, the elution container <NUM>, the cleaning container <NUM> and the regeneration container <NUM> are connected to the respective pipes <NUM> to <NUM>. The valves 18a-e, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, 81a, 82a, 83a, 121a, 122a and 123a, the second branching connector <NUM> and the additional pump <NUM> are controlled to make flow:.

The treatment can proceed continuously, employing again the same phases as those described above.

Of course, here, the treatment began with the placing in series of the columns 99c and 99b but it could begin with the placing in series of for example the columns 99b and 99a or 99a and 99c.

Furthermore, it is to be noted that the manual valves 190a-c are by default open during the whole of the chromatography treatment, provided that the columns 99a-c are connected on the circuit. They are closed when the treatment is terminated and the columns 99a-c are removed from the circuit of the installation.

Claim 1:
An installation for treating biological liquid by chromatography, generally extending in a longitudinal direction and comprising:
- at least one supply valve (20b) for supplying biological liquid to treat, configured to be connected to at least one biological liquid supply container (<NUM>);
- at least one supply pump (<NUM>) disposed downstream of said at least one supply valve and connected to the latter;
- a plurality of instrument members disposed downstream of said at least one supply pump, including distribution valves (81a-c, 82a-c, 83a-c) and devices (78a-c, 85a-c, 86a-c) for measuring physico-chemical parameters of the biological liquid, and which are connected to said at least one supply pump;
- a plurality of chromatography columns (99a-c) disposed downstream of said plurality of instrument members, each of said chromatography columns being directly associated with and connected to at least some of said instrument members, and being configured to be supplied with biological liquid by said at least one supply pump; and
- a plurality of single-use pipes configured to be connected to said at least one supply valve, to said at least one supply pump, to said plurality of instrument members and to said plurality of chromatography columns, so as to form at least one supply line for supplying biological liquid (<NUM>) to treat of a treatment circuit of said installation;
characterized in that said chromatography columns are disposed (99a-c) relative to each other in a direction of extension generally transverse to said generally longitudinal direction of extension of said installation; and
in that some of said instrument members associated with said chromatography columns (99a-c) are mounted on dedicated control and actuation platforms (80a-c) which are disposed in the same general transverse direction as said chromatography columns and which are substantially above said respective chromatography columns.