FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patent Rules 2005
PROVISIONAL/COMPLETE SPECIFICATION
(see sections 10 & rule 13)
1. TITLE OF THE INVENTION
Continuous Countercurrent Fluidized Moving Bed (FMB) and/or Expanded
Moving Bed (EMB)
2. APPLICANT (S)

NAME

NATIONALITY ADDRESS

Arvind Mallinath Lali
Indian National
Chemical Engineering Department
Institute of Chemical Technology,
Nathalal Parikh Marg,
Matunga ( East),
Mumbai- 400 019, Maharashtra,
India
3. PREAMBLE TO THE DESCRIPTION
PROVISIONAL SPECIFICATION
The following specification describes the inventton and the manner in which it is to
be performed.

Field of the Invention
The present invention relates to the design and use of fluidized moving bed (FMB) and/or expanded moving bed (EMB) more specifically in a multistage continuous countercurrent arrangement applicable for processes that involve adsorptive separation and/or reactions involving molecules large or small.
Background of the Invention (Prior Art)
Adsorption processes have been used for a number of different applications such as to carry out separations and variety of chemical reactions. From the point of view of the contactor design for adsorption, fluidized bed and expanded bed adsorption are innovative techniques. These adsorber designs enable process engineers to discard tedious and expensive steps like filtration, clarification, and concentration steps prior to selective adsorption, as adsorbent particles are fluidized or suspended in flowing fluid , to allow particulate matter-containing solution to flow freely through the bed of adsorbent without causing clogging or blockages. In addition, these techniques also deliver a clarified stream containing purified product or a product suitable for further purification and processing. Of these two techniques an expanded bed offers advantages of low back mixing through providing stabilized fluidized bed of properly designed adsorbent particles.
However, employing fluidized bed, expanded bed or packed bed of adsorbent particles has a disadvantage that they are batch operations, and require large volumes of adsorbent particles especially for large scale operations.. Further, due to a significant portion the adsorbent often remaining in saturated state or waiting to come in contact with the sol.utes during passage of the adsorbent zone passing through the conventional packed, fluidized or expanded bed, and due to the fact that a typical adsorptive purification cycles requires multiple steps of batch operations in sequence like equilibration, loading, washing, elution and regeneration, the overall productivity of the adsorbent expressed as kg solute/s

purified per hour per liter of adsorbent becomes low especially as volume of the adsorbent bed becomes large for large scale operations.
Several attempts have been made to design continuous countercurrent adsorption contactors to circumvent above problems:
Technical paper by Ryan 0. Owen, Graham E. McGreath and Howard Chase, "A new approach to continuous counter current protein chromatography: direct purification of maleate dehydrogenase from a Saccharomyces cerevisiae homogenate as a model system", Biotechnol. Bioengg. 53 (4), 427-441 (1997) described expanded bed for continuous chromatographic purification. The system has several problem areas and requires continuous manipulation to maintain constant bed height. Also the adsorbent extractor used for removal of adsorbent makes the design complicated and affects the stability of expanded bed.
Burns, M. A. and D. J. Graves, "Continuous Affinity Chromatography Using a Magnetically Stabilized Fluidized Bed", Biotechnology Progress 1, 95-103 (1995) suggested a two-column magnetically stabilized fluidized bed system for the continuous chromatography of biochemical products. The magnetically stabilized fluidized bed system is generally considered to be complicated and expensive.
Gordon, N. F., H. Tsujimura and C. L. Cooney, "Optimization and Simulation of Continuous Affinity Recycle Extraction", Bioseparation 1, 9-12 (1990) described a process using well-mixed flow reactors as opposed to fluidized bed and reported the continuous affinity recycle extraction of proteins. This system, although simple and easy to control, has the disadvantage of employing a stirred tank system which gives low efficiency per stage and large processing volumes are essential for even moderate throughputs.
US Patent No 6,716,344B1, for "Liquid solid circulating fluidized bed", (2004), and US Patent Publication No. 2004/0226890A1 "Method for recovering ionic products" (2004) discloses a liquid solid circulating fluidized bed (LSCFB)

preferably for use as an ion exchanger, and consists of two fluidized bed columns, one fluidized bed adsorber (downcomer) operating in conventional fluidized bed mode for adsorption of ions of interests and wherein the upflowing fluid keeps the adsorbent particles fluidized and the adsorbent particles themselves are in net downward flow and out of the bed into the second fluidized bed that operates in riser mode and carries the adsorbent particles up in concurrent flow of eluting medium while performing solute desorption of ions to provide eluted solute as well as regenerated adsorbent particles. Fruther, according to the invention, the Ion exchange adsorbent particles are separated and re-fed into the top of the first adsrobent downcomer bed. Thus in effect, the adsorbent particles are circulated continuously between the riser and the downcomer i.e. the particles that have adsorbed ions in the adsorber are passed from the downcomer to the desorber riser where elution occurs and the particles are returned to the adsorber near the top of the adsorber column. Such a two stage downcomer-riser combination of expanded and fluidized beds in an LSCFB can be used in processes for continuous recovery of ions of interests. However, the apparatus disclosed is useful only for single stage operations wherein only one component adsorbs and eluted to give regenerated adsorbent, or a set of components adsorbs and is eluted as the set of adsorbed components to give regenerated adsorbent. Further, two operations namely, elution and regeneration are performed together in same column (riser) in co-current mode, thus having low elution efficiency and leading to diluted elution of adsorbed component while also in many cases resulting in insufficient regeneration of the adsorbent. The apparatus disclosed does not consist of separate chambers or sections for elution and regeneration of adsorbent particles for the cases where separate steps are required for selective elution of adsorbed component and regeneration of adsorbent particles. Further, another disadvantage of the system is the fact that for steady operation the system requires stringent pressure balance for the desired circulation of solids.

US Patent No. 3,879,287, "Continuous ion exchange process and apparatus" (1975) relates to an apparatus for continuous ion exchange separation. However, the process described is a semi-continuous process as the recommended eluting means is a batch wise conventional fixed bed ion exchange process.
US Patent No. 4,279,755: "Continuous countercurrent ion exchange process" (1993) relates to a continuous countercurrent ion exchange process for absorbing ions of interest onto ion exchange particles from a feed liquor containing ions which when absorbed on the particles cause the density of the particles to increase. The process comprises the steps of (1) flowing the feed liquor upwardly through a main bed of ion exchange resin particles contained in a main chamber of an absorption column and thereby maintaining the bed in fluidized state; (2) continuously collecting the denser loaded particles from the lower region of the absorption column; (3) passing an outflow of the feed liquor from the upper region of the main chamber upwardly into the lower region of the polishing chamber containing a secondary bed of fluidized ion exchange resin particles whereby residual ions of interest are polished from the liquor, and (4) producing a barren liquor flowing out of the upper region of the polishing chamber. This invention is also a semi-continuous process as the stripping and the regeneration of the loaded ion exchange particles cannot be performed in this device.
Further, US Patent No. 3,207,577; US Patent No. 3,235,488; US Patent No. 3,152,072; US Patent No. 3,240,556; US Patent No. 3,551,118; US Patent No. 4,018,677; US Patent No. 4,035,292; US Patent No. 4,035,292 and US Patent No. 4,035,292 incorporated herein for the purpose of reference do not disclose the apparatus, and in particular, the fluidized moving bed and/or expanded moving bed for continuous counter-current contact between a liquid to be treated and solid particles wherein the steps of adsorption, washing, elution and regeneration, are carried out in continuous countercurrent mode.

Thus the designing of new continuous countercurrent fluidized/expanded moving bed having high efficiency and productivity is desirable.
Brief description of the present invention
It is an object of the present invention to provide a single or multistage continuous countercurrent fiuidized moving bed and/or expanded moving bed for recovery and purification of single or multiple component/s of interest, for example biomolecules, synthetic/semisyntbetic active pharmaceutical ingredients, intermediates, derivatives, contaminants/impurities, value added products, metals etc., by contacting liquid mixture containing the component/s with the solid adsorbent in countercurrent mode. It is also an object of the present invention to provide efficient equipment and process for continuous recovery and purification of molecule/s from a mixture and performing not only the adsorption but also the washing, elution, regeneration and equilibration steps using respective different or similar liquid phases and contacting the liquid phases and solid adsorbent in a continuous countercurrent mode. Further, it is also an objective of the present invention to design the equipment with independent control over process variables at every stage for total ease and control of ease of each of the operations namely adsorption, washing, elutions, regeneration and equilibration.
The present invention relates to a composite fiuidized moving bed and/or expanded moving bed system comprising a first stage/column, operating in fluidized/expanded bed mode, to which the solids are continuously fed from the top, and are continuously taken out from the bottom of the first stage/column after specified residence time, wherein the net movement of the solids is against the liquid flowing in upward direction through the stage/column, and sedimenting solids from the first stage/column are continuously fed to the top of the second stage/column, also operating in fluidized/expanded bed mode, where once more its countercurrent contact with up flowing liquid is carried out. The sedimenting solids from the second stage/column are now removed from the bottom of the

second stage/column and fed to the top of the third stage/column also operating in fluidized/expanded bed mode, and is further carried to the next stages/columns in same manner The system described herein can be a single or multistage/column depending upon number of stages involved or required in the process. The sedimenting adsorbent solids from the last fluidized bed or expanded bed stage/column are taken out continuously and fed back to the top of the first stage/column, through a feed hopper to which the adsorbent solids are transported by means of pump or liquid solid ejector, or any other suitable device known to those skilled in art, and wherein the feed hopper is suitably designed and operated, for examples in fluidized/expanded bed mode, in such a way to deliver the solids to the top of the first stage/column continuously in a controlled manner.. The flow of the adsorbent phase from one stage to another in downflow sedimenting mode is controlled by valves that can be operated between the stages.
Preferably the system comprises of five stages/columns for sequentially carrying out adsorption/binding, washing, desorption/elution, regeneration/cleaning-in-place/sanitization-in-place and equilibration/conditioning of adsorbent particles in a continuous and counter current mode.
Preferably the system described comprises of four stages/columns for carrying out first four steps as described above, and performing the equilibration step in the feed hopper itself by providing equilibration liquid for the expansion of adsorbent particles in the feed hopper, so as to have slurry of required concentration, and is fed at the top of the first stage/column. Hence, the hopper can serve the dual role of equilibration as well as providing fresh/regenerated solids to the top of first stage/column at required solid concentration and flow rate.
Preferably all the expanded/fluidized bed stages/columns are vertical columns stacked one over the other and solids are transported from one stage/column to another stage/column through a solid transport line, connecting the bottom of the

one stage/column and the top of the another stage/column, and flow of solid adsorbent slurry through the said solids transport lines is controlled using valves.
Preferably the feed, washing liquid, desorbent/eluent, regenerant, and/or equilibration liquid phases are fed to the respective stage/column, through a central distributor, located at some specified height from the bottom of the respective stage/column, or through a perforated plate distributor, and the discharge of said liquids fed to the respective stage/column is done through the outlet located at the top of respective stages/columns.
Preferably while the said main liquid phases like feed, washing liquid etc as stated above, are fed to the respective stages/columns through the said central distributor located at the specified height from the bottom of the respective stage/column, or through a perforated plate distributor, and an auxiliary liquid flow is given through another perforated plate distributor located at the bottom most portion of the respective stage/column, for washing of adsorbent solids as well as keeping the solids in suspended fluidized state in a section that can be called an auxiliary fluidized section, and to ease the control of its flow to the stage/column below or in to a solid reservoir in case of the last bottom stage/column. The solid adsorbent particles sediment at some adjusted net flow rate through one or more openings or downcomers tubes provided from the perforated plate auxiliary flow distributors or from the auxiliary fluidized sections (see Figures 1, 2, 3 and 4). The downcomer tubes are equipped with valves that control the solid slurry flow from an upper stage/column to the lower stage/column and open at the top of the lower next expanded or fluidized bed of adsorbent in that stage/column.
Preferably solids are transported from one stage/column to another stage/column through one or more solid downcomer tubes from the auxiliary distributor plate or auxiliary fluidized section. The downcomer tubes, which open at top of the next lower fluidized/expanded bed, is of sufficient length so as to dip well in to the liquid phase in the lower stage/column but yet clear above the expanded/fluidized

bed of adsorbent phase, this so to prevent the loss of solid through over flow with outgoing liquid.
The heights of the stages/columns stacked one over the other, may or may not be same, and may vary according to the process requirements. Preferably the height of the expanded/fluidized adsorbent bed in each stage/column is maintained by controlling solid inventory in every stage/column and the flow rate of the respective liquid phase.
Preferably the means of connecting one stage/column to another stage/column further includes washer zone for washing of solid particles before they fed to the top of the next stage/column through one or more downcomer lines.
Preferably the first top stage/column is an adsorber, operating in countercurrent fluidized bed/expanded bed mode, and wherein the some or all the component/s in the feed coming in through the primary central distributor adsorb on the adsorbent particle phase. The countercurrent settling adsorbent phase with adsorbed component/s is washed in countercurrent mode in the same stage/column by upflowing auxiliary fluid coming in through bottom perforated distributor in the auxiliary fluidized sections. The adsorbent phase is carried to the next lower or second stage/column through the downcomer tube/s. This second stage/column serves as washing stage wherein the settling particles are washed in a countercurrent fashion by the liquid moving in upward direction, and so washed said adsorbent particles is being carried to the next stage/column in the same fashion as they came in through the first column, with the difference that in the second stage both primary and auxiliary phases are simply the washing liquid phase. The next lower stages/columns are desorbers wherein the said adsorbent particle phase is sequentially contacted with desorbing liquid/s in countercurrent fashion to desorb the one or more adsorbed component/s from the said adsorbent phase, and adsorbent phase after desorption is carried to the next lower stage/column for regeneration in countercurrent mode by treating with a suitable regenerating liquid phase. The regenerated solid adsorbent phase now

passes in to the next and last equilibration or conditioning stage/column by suitable equilibrating liquid. Alternatively, the solid phase after regeneration stage/column can directly pass into the solid reservoir at the bottom of the entire vertical assembly. In case where the equilibrating stage/column is used, the solid phase slurry passes from its bottom into the solid reservoir. The regenerated or equilibrated adsorbent phase collected in the bottom solid reservoir is re¬circulated to the solid feed hopper located at the above the top first stage/column or directly passed at a controlled flow rate in to the top of the first stage/column. The transportation of the regenerated or equilibrated solid phase to the top is performed using a pump or a combination of one Or more liquid-solid ejectors and hydraulic transport in flowing liquid.
Preferably also the stage/column, wherein the desorotion/elution is carried out in countercurrent mode provides regenerated adsorbent particles and is re¬circulated to the solid feed hopper or to the top of the top first stage/column after equilibration in the manner as described above.
Preferably also the adsorbent particle phase is washed at the bottom of every stage/column before entering into the next stage/column, by an auxiliary liquid flowing through the perforated distributor located at the bottom of every stage. The primary liquid phase in each stage/column is fed in through the central distributor located at a specified height above the bottom of each stage/column. The combined flow rate of primary and auxiliary liquid phases flowing upward maintains the solid particle adsorbent phase m a downward settling fluidized/expanded state.
In one embodiment of the present invention the stages/columns are stacked one over the other and each connected to the next section below by way of one or more downcomers tubes that pass solid particle phase downwards while keeping the main liquid mobile phase in the two sections segregated. In another embodiment of the present invention one stage/column is placed alongside the other and at same or different elevation, and in circular or any other arrangement

known to those skilled in art. The number of such stages/columns depends on number of steps involved in the process. Solid particles were taken out from the bottom one stage/column and transported to another stage/column by means comprising pump, hopper ( such as hydro-cyclone) and solid transport lines or liquid-solid ejector, hopper (such as hydro-cyclone) and solid transport lines or any other means known to those skilled in art. The said sofid particles from the last stage/column are transported back to the first stage/column by means of solid transportation system above. Each stage/column of the present invention is operated continuously in countercurrent mode and having independent control.
Preferably the entire FMB or EMB assembly can be used to recover and/or purify component/s from the mixture by adsorption using ionic, non-ionic or zwitterionic modes of interactions. The mixture of components may be obtained by chemical/biochemical synthesis such as chemical reaction, enzymatic transformation/catalysis; biosynthesis in fermentation by genetically modified, improved or unmodified microorganisms; from plant/s or plant cell culture, animal/s or animal cell culture; transgenic plants; transgenic animals; sea water; waste water from any industrial or other activity; and/or combination of one or the other of all the above, in a suitable way known to those skilled in the art.
Preferably the component/s adsorbed is/are ionic, non-ionic or zwitterionic and is/are large molecule/s such as protein/s, polysaccharide/s, nucleic acid/s, protein aggregates, endotoxins etc. and obtained by means of any of the sources or techniques as described above.
Preferably the component/s adsorbed is/are ionic, non-ionic or zwitterionic and is/are small molecule/s such as peptide/s, vitamin/s, antibiotic/s, steroid/s, sug.ar/s, metal/s or any known chemical/biochemical compound and derivatives thereof.

Preferably the component/s adsorbed is/are micro or nanoparticle/s such as plant/animal/microbial cells, gene therapy vectors, viruses, virus like particles, phages etc. or particles having similar nature.
Preferably the apparatus described herein is used for to carry out chemical or biochemical reaction combined with adsorptive purification in an integrated or non-integrated manner.
Preferably the feed liquid used for the recovery and/or purification of component/s, such as fermentation broth containing solid or particulate matter and relatively low concentration of target component/s. In such cases the traditional choice of unit operation for handling of solid or particulate matter is either filtration or centrifugation or combination thereof, which not only adds in the operational and capital cost but also leads to increased product loss due to additional step in processing. The continuous countercurrent fluidized moving bed and/or expanded moving bed (FMB and/or EMB) system of the present invention is an integrated unit operation which can perform recovery and purification of component/s from unclarified feedstocks such as containing suspended solid or particulate matter.
Preferably the system operates continuously in fluidized or expanded moving bed mode with countercurrent contact of solid phase with liquid mobile phase in all stages/columns, wherein the solids are adsorbent particles or catalyst particles, porous or non-porous, and are commercially available or prepared by any means known to those skilled in arts.
Preferably the system operates continuously in expanded or fluidized moving bed mode with countercurrent contact of settling solid particles with upflowing liquid in all stages/columns, wherein the solids are the adsorbent particles or a catalyst and is commercially available or prepared by any means known to those skilled in arts.

The system is useful not only for efficient adsorption but also for efficient and low volume desorption, regeneration, and equilibration of adsorbent or catalyst particles. Thus the invention eliminates the need for additional and separate unit operation/s as well as circumvents the problems associated with conventional batch, semi-continuous or continuous (adsorption) processes.
In the present disclosure, the singular forms "a", "an", and "the" include plural reference also unless the context clearly dictates otherwise. Thus, for example, a reference to "stage/column" includes singular or a plurality of such stages/columns, and a reference to "liquid" is a reference to one or more liquids equivalents thereof known to those skilled in the art. Similar syntactical principal also applies to other examples such as adsorbent, component, solid transport line and valve.
Brief description of the drawings
Further features, objects, and advantages will be evident from the following detailed description of the preferred embodiments of the present invention taken in conjunction with the accompanying drawings.
Detail description the preferred embodiments of the present invention
Referring to Figures 1,2 3 and 4 the present invention consists of number of fluidized/ expanded bed stages/columns equal to the number steps like adsorption, washing, elution, regeneration, equilibration etc. involved in the desired operation of the process. These stages/columns are stacked one over the other, each connected to the next section below by way of one or more downcomers tubes that pass solid particle phase downwards while keeping the main liquid mobile phase in the two sections segregated. Each stage/column of the present invention is operated continuously in countercurrent mode and having independent control.

Feed tank 1 is used as the feed hopper to charge the fresh or recycled regenerated and/or equilibrated solid particle phase (for example adsorbent particles) to the top of the first stage/column through top solid transport line 2, wherein the solid slurry flow rate is confroJJed by valve 3. Solids In the feed hopper 1 are kept in fluidized/expanded state on a flow distributor plate 5 by a liquid such as water or the equilibration liquid phase charged through bottom inlet 4 of feed hoppeM. The feed hopper 1 is provided with top outlet 6 for the discharge of excess liquid entering into the hopper, and means 7 of filtering the said liquid to retain and avoid any loss of solids.
In the preferred embodiment of the present invention the first stage/column 8, to which the solids are fed at the top through top solid slurry feed line 2, is provided with a device 9 at the opening of the opening of the solid feed line 2 that ensures even dispersion of solids in the primary or main expanded/fluidized bed section or the first stage/column 8. The primary liquid (for example, feed containing the adsorbing solute) is fed to the first stage/column 8 at the bottom through inlet 10 and is distributed evenly to the stage/column 8 through the distributor which is either perforated plate distributor 53, as here in Figure 1 and Figure 2, or a central distributor 11 as in Figure 3 and Figure 4. The secondary or auxiliary liquid is pumped through the inlet 12 and is passed in upward direction through the perforated plate distributor 13 or 55 which supports the down settling solid phase in expanded/fluidized state in what is called the secondary or auxiliary section 65. The combined liquids, primary plus secondary fed to the first stage/column, now comprising the primary or main section and the secondary or auxiliary section, are discharged at the top of the main section 8 through the outlet 57-b as in Figure 1 and 2, and outlet 14 as in Figure 3 and 4. The liquid flowing in upward direction through the said first stage/column 8 is adjusted to a given flow velocity that keeps the solids in fluidized/expanded bed mode, wherein the contact of the said solids to the said upward flowing liquid is countercurrent to the down settling solid phase thus leading to higher efficiency of the stage/column 8 compared to cases wherein solids remain with zero net flow as in

traditional packed or expanded/fluidized beds. The sedimenting solids are continuously removed from the bottom of the stage/column 8 as they pass into the auxiliary section through one or more solid downcomer lines or tubes located centrally 15 (Figures 3 and 4) or as side arms 16 (Figures 1 and 2). The solid flow rate in the downcomer is controlled by a valve 17 (in Figures 3 and 4) or 18 (in Figures 1 and 2) respectively, and are fed to the top of the next stage/column 20. The distributor 11 (Figures 3 and 4) or 53 is located at a specified height 19 from the perforated plate distributor 13 or 55.
In the preferred embodiment of the present invention the design of stage/column described above (schematically shown in Figures 1, 2, 3 and 4) is used for the design of single stage, two stage or multi-stage/column fluidized moving bed and/or expanded moving bed system depending upon the number of steps desired in a process.
In the preferred embodiment of the present invention referring to Figure 2, the first stage/column, wherein the primary liquid is charged through the inlet 52 and passed through the distributor 53, and secondary or auxiliary liquid is charged through inlet 54 and passed through distributor 55. Both liquids flows in upward direction against the sedimenting solids, and are discharged through the outlet 56 located at the top of the said stage/column. The liquid flowing in upward direction keeps the solids in fluidized/expanded state, whereby the contact of the solid particles with the liquid is countercurrent. There is provided a zone, for example washing zone, between the two distributors 53 and 55, also called the secondary or auxiliary section 65. The solids are carried from one stage/column to another stage/column by side arm 16, controlled through valve 18.
In the preferred embodiment of the present invention the design of stage/column described above (for Figure 2) is used for the design of single, two stage or multi¬stage/column fluidized moving bed and/or expanded moving bed system depending upon the number of steps in the process.

In the preferred embodiment of the present invention the solids from the last stage/column 32 are removed continuously from bottom downcomer outlet 39, and are collected in a tank 42, where the solids may be or may not be kept in suspension by means of stirring 43, or by using a liquid fed through bottom inlet. These solids are continuously transported to feed tank 44 equipped with a slurry pump or a liquid solid ejector 45. Alternatively, the downcomer of the auxiliary section of the stage/column can also discharge solids directly in to the feed tank 44. Backflow of slurry of solids is prevented by using non return valve 46 located in solid transport line 47 connecting to tank 42 and feed tank 44 with the liquid solid ejector 45. The said solids are then continuously fed to the top feed hopper 1 using liquid solid ejector 45. The feed tank 44 is provided with a nozzle 48 at an optimized distance, and the driving liquid required to carry the solid particles to the hopper 1 i'S pulr??ped through said nozzle 48 using pump 49. Alternatively, the solids collected in the tank 42 can be transported to the hopper 1 by using pump 51 as shown in Figure 2. The said slurry is fed continuously to the hopper 1 through inlet 50. The said inlet 50 can be at the top 0f the hopper 1 or may be at the bottom 4. Solids received by the hopper 1 in the manner described can be fed in controlled manner to the top of the first stag^/column 8 continuously as explained above.
In the preferred embodiment of the present invention referring to Figures 1 to 4 the stages/columns arranged one above the other to provide a two or multi¬stage/column system, wherein first stage/column tj js connected to second stage/column 20 in the manner described above, ancj so on till the n number of stages/columns determined by the specific process steps required in the operation. The bottom last stage/column 32 from which the solids are removed and are re-circulated to the top of the first stage/column 8, using liquid solid ejector 45 or pump system 51, and through the hopper 1 continuously at a required solid concentration and flow rate.
In the preferred embodiment of the present invention referring to Figure 1 the said solids coming from top feed hopper 1 can be taken to a stage/column 57

before entering into first stage/column 8, and which works like the auxiliary section described above, and whereby the said solids can be continuously washed or equilibrated. The solids in the stage/column 57-a are kept in the fluidized/expanded state by a liquid injected through inlet 58 flowing in upward direction. In the said stage/column 57-a the contact of the said solids and liquid is countercurrent.
In the preferred embodiment of the present invention referring to Figure 1 to 4 wherein the function of the first stage/column 8 is continuous adsorption of target component/s on the solids (preferably adsorbent particles) in a countercurrent mode, from the feed liquid charged through the inlet 10 or 52. The solids to which the target component/s is adsorbed are continuously washed in the same stage/column (as shown in Figure 2 and 4) by the secondary/auxiliary liquid charged through inlet 12 in the continuing secondary or auxiliary section 65. Alternatively, the said solids can be continuously taken to intermediate stage/column 59 (as shown in Figure 1 and 2) through solid transport line 60, wherein the said solids are washed countercurrently by a secondary/auxiliary liquid injected through inlet 54 in a separate auxiliary section 65. The said solids (to which the target component/s is adsorbed) after washing are continuously carried to the second stage/column 20 which is also equipped with a primary main followed by the auxiliary section in the same manner as stage/column 8. through one or more downcomer tubes or solid flow line 15 or 28, wherein the target component/s are desorbed/eluted by a liquid injected through the bottom inlet 22 and/or 24. For the recovery and/or purification of individual component from mixture of components adsorbed on the said solids (in the first stage/column) can be carried out by adding number of said second, third, fourth and so on stages/columns after said first stage/column depending upon number of individual components or group of component/s required to be isolated, and arranged in the same manner as the top two stages/columns. The said solids in the second stage/column, or the last elutlon stage/column, after desorption/elution of all desired components, gives the regenerated solids, which

are carried to the next stage/column through solid transport for the regeneration. The regenerated solids can be then equilibrated in the last stage/column 32 by an equilibrating liquid injected through inlet 34 and/or 36 (as shown in Figures 3 and 4) or through inlet 61 or 64 (as shown in Figures 1 and 2) in a countercurrent mode. The said equilibrated solids from the l§st stage/column 32 are continuously removed and transported to the top of the first stage/column 8, using liquid solid ejector 45 or by pump system 51, through feed hopper 1 for reuse/recycle of the solids in the FMB/EMB system.
Alternatively, the bottom last stage/column in the system (32 in Figures 1 to 4) can be used for the continuous regeneration of the said solids in countercurrent mode, by injecting a regenerant liquid through the inlet 34 and/or 36 (as shown in Figure 3 and 4) or through inlet 61 or 64 (as shown in Figure 1 and 2). In the case the regenerated solids are continuously removed from the bottom of last stage/column 32 and are transported to top of the first stage/column 8 using liquid solid ejector 45 or by pump system 51, through feed hopper 1. Here the hopper 1 performs the function of equilibration of the said solids, and supply of equilibrated/fresh solids to the fist stage/column through top solid transport line 2 for reuse/recycle of said solids
Prospective Applications of the Technology
The prospective applications of the invention that the invention is supposed to be appropriate for comprise but are not limited to:
i) Adsorption chromatographic and/or negative adsorption
chromatographic recovery and purification of component/s from biological or non-biological sources
ii) To carry out the chemical or biochemical reactions such as enzymatic transformation/catalysis, and/or further integration of recovery and purification of the product and/or impurities generated by said processes

iii) For integrated recovery and/or purification of fermentation (for example microbial fermentation) or cell culture (animal, plant) based products in an integrated or non integrated manner
iv) For the recovery and/or purification of products obtained from transgenic plants or animals
v) For the recovery and/or purification of products from genetically engineered microbial sources, plants, animals etc.
vi) For the recovery and/or purification of multiple products from single feedstock, chemical or biotechnological, or natural.
vii) For recovery and/or purification of synthetic active pharmaceutical ingredients, intermediates, or derivatives from reaction mixture
viii) For the recovery and/or purification of metals or their salts or other derivatives, from their mixtures with other metals, their salts or derivatives, and/or other compounds
ix) For the recovery and/or purification products from sea water, waste water, or for desalination of sea water and for waste water treatment.
x) For the recovery and/or purification of products which are ionic, non-ionic or zwitterionic as mentioned above or other products obtained by synthetic, semisynthetic or biosynthetic way known to those skilled in art and has resemblance similar to that of products mentioned above
Thus the present invention can be easily applied to an industrial level.
The following is the example carried out to demonstrate the present invention. However the present invention should not be construed as limited to the description of the example.
Example
In the arrangement shown in Figures 1 to 4, the top hopper 1 is an acrylic cylinder of 30 cm diameter and 50 cm height. Outlet of the hopper for transporting the solids to the top of the first stage/column 8 is 1.5 cm diameter

acrylic pipe, wherein the solid flow is controlled through valve 3. The main column consists of three stages/columns 8, 20 and 32 made of glass columns with each stage/column having 10.5 cm inner diameter and 72 cm height. Inlets and outlets for the liquid are provided at the bottom and at the top of each stage/column via a glass pipe having 1.0 cm inner diameter. Distributor to each stage/column is a 0.3 cm thick stainless steel plate, over which is placed a 50 micron wire mesh. The distributors are incorporated between each two consecutive stages/columns As in Figure 1 to 4. The bottom distributor has central solid transportation line of 0.625 cm diameter and of height sufficient to deep inside the next stage/column at a level below the top liquid outlet. A quarter inch valve (for example 17, 29, 41 as shown in Figure 1 and 3) is provided in the central solid transport line to control the solid flow. A conical distributor as in Figure 1 and 3, used for feeding primary liquid, is of outer diameter 8.0 cm, giving concentric opening of 2.5 cm between said distributor and the glass column. This distributor is fixed at 10 cm height above bottom of particular stage/column. The distance between said two distributors forms a washing zone, used for washing of solid in countercurrent mode by up flowing liquid. The last stage/column 32 has bottom outlet 39 to remove the solids continuously, which are then transported to top of the first stage/column 8 through an acrylic hopper 1, by glass liquid-solid ejector 45 or pump (diaphragm pump system) system 51. Further, the experiment carried out using the fluidized moving bed and/or expanded moving bed apparatus as described above, with chicken egg white extract for the recovery and purification of lysozyme (Table 1).
Table 1: summary of the parameters and results of the lysozvme recovery and
purification using FMB/EMB
Parameter Result
Feed protein concentration, mg/ml 56.6
Feed lysozyme activity, U/ml 2.00 * 105
Total lysozyme activity loaded, Units 4.83* 109

specific activity of feed, Units/mg 3556
Total protein loaded, mg 1.36 x 106
Flow velocity, cm/hr 277
Total eluted protein, mg 26579
Total lysozyme activity recovered, Units 4.68 x 109
Yield, % 97
Specific activity, Units/mg 1.76 x 105
Purification factor 49.58
Production rate, KUnits/hr/Liter of adsorbent) 7.81x 105
Lysozyme purity, % 98.68



The specific activity of lysozyme and protein content in the feedstock prepared after dilution to 40% (v/v) with sodium acetate buffer (pH 4.5) were assayed at about 3556 U/mg and 56.6 mg/ml respectively. This solution was fed to the first stage/column for adsorption on adsorbent particles (SEPABEADS EB-CM, from Resindion s.r.l., Italy) and liquid exhausted with respect lysozyme was discharged through top outlet. The adsorbed lysozyme was washed in the same stage in washing zone with sodium acetate buffer as auxiliary liquid followed by elution in second stage/column. Further, the regeneration of the adsorbent media was carried out in third stage/column with 0.5M sodium hydroxide solution. Finally regenerated adsorbent particles were equilibrated in hopper with sodium acetate buffer and re-circulated to the top of first stage/column. All steps of adsorption, washing, elution, regeneration and equilibration are carried continuously. During the operation solids are contacted with feed, washing, elution and regeneration liquid in countercurrent mode. This has enhanced the efficiency of the process terms of produntivitv