Expanded Bed Adsorption Process Research Articles

Hydrodynamics of expanded bed adsorption studied through CFD-DEM

The hydrodynamics of the Expanded Bed Adsorption process is studied through simulations combining Computational Fluid Dynamics and the Discrete Element Method. A representative base case is defined, based on process design parameters commonly encountered in literature. Then, 19 other cases are defined, each representing a singular adjustment to the column design, material properties, or operating conditions. The parameters that are varied are the expansion factor, liquid viscosity, bed aspect ratio, mean particle density, width of the particle density distribution, width of the particle size distribution, column taper angle, and column alignment angle. The impact of each adjustment on the bed behaviour is discussed, using the local particle size distribution and solids dispersion coefficient as main indicators of bed stability. Optimal performance was found for an expansion factor of two to three, and the combination of particle size distribution and particle density distribution was found to greatly improve bed stability. The mixing process of the liquid and solid phases is concluded to be of highly complex nature, and cannot simply be predicted from the liquid flow velocity.

PlasmaCap EBA: An innovative method of isolating plasma proteins from human plasma.

The growing demand for immunoglobulin (IG) requires development of improved plasma fractionation methods to provide higher yields in a cost effective, scalable manner without compromising product purity and efficacy. A novel protein extraction method, utilizing expanded bed adsorption (EBA) chromatography, has been developed. PlasmaCap IG (10% liquid formulation intravenous IG [IVIG]) is the first plasma-derived product manufactured using PlasmaCap EBA technology. The PlasmaCap EBA platform consists of a series of consecutive columns which bind a target protein, or group of proteins, in their native state directly from cryo-poor plasma. EBA chromatography includes five key steps: (1) expand, (2) sanitize and equilibrate, (3) load, (4) wash and (5) elute. These steps are made possible using high-density tungsten-carbide agarose beads, suspended by upward flow. The PlasmaCap EBA process was evaluated during Evolve's clinical campaign for scalability, product quality and yield. PlasmaCap EBA technology can be predictably scaled by maintaining the minimum residence time and residence time distribution for EBA columns of different diameters. Scalability of the manufacturing process was demonstrated by the 50-fold volumetric increase from laboratory-scale lots to clinical-scale lots. The process is also associated with enhanced product purity, such as lower aggregates. The PlasmaCap EBA process is expected to have the same or better yield and purity at commercial scale production compared to the clinical campaign. The PlasmaCap EBA platform was used to successfully develop PlasmaCap IG (10% liquid formulation IVIG) with proven scalability, product quality and yield.

Printed monolith adsorption as an alternative to expanded bed adsorption for purifying M13 bacteriophage

An ordered 3D printed chromatography stationary phase was used to purify M13 bacteriophage (M13) directly from crude cell culture. This new approach, which offers the same advantages as expanded bed adsorption (EBA) with regard to tolerating solids-laden feed streams but without the corresponding issues associated with fluidized bed stability that affect the latter, can be described as “printed monolith adsorption (PMA)”. PMA columns (5, 10 and 15 cm length by 1 cm diameter) were made via a wax templating method from cross-linked cellulose hydrogel and functionalized with a quaternary amine ligand. The recovery of M13 was found to be strongly linked to load flow rate, with the highest recovery 89.7% ± 6% for 1.4 × 1011 pfu/mL of resin occurring at 76 cm/h with a 10 cm column length. A recovery of 87.7% ± 5% for 1.49 × 1011 pfu/mL of media was achieved with a 15 cm column length under conditions comparable to a reported EBA process. The PMA process was completed three times faster than EBA because PMA flow rates can readily be adjusted during operation, with high flow rates and low back pressure, which is unique to the ordered monolithic media geometry used. Equilibration, wash, and cleaning steps were carried out at high flow rates (611 cm/h), minimizing process time and were limited only by the volumetric flow rate capacity of the pumps used, rather than column back pressure (<0.1 MPa at 611 cm/hr). Initial capture of M13 appears to occur on the surface of the monolith solid phase (i.e. the mobile phase channel walls) and subsequently, at a slower rate, within the internal pores of the solid phase media. The difference in binding rate between these two sites is likely caused by slow pore diffusion of the large M13 particles into the pores, with similar slow diffusion out of the pores resulting in tailing of the elution peak. The results indicate that PMA is a promising technology for the efficient purification of viruses directly from crude cell culture.

κ-Carrageenan-Fe2O3 superporous composite adsorbent beads for application in magnetic field expanded bed chromatography adsorption

One of the authentic separation methods to purification of bioproducts is expanded bed adsorption (EBA). The magnetic field expanded bed adsorption (MFEBA) can be used to improve the efficiency of the EBA process. New type adsorbent beads composed as κ-Carrageenan-Fe2O3 (KC-Fe2O3) and superporous κ-Carrageenan- Fe2O3 (SP-KC-Fe2O3) have been prepared and well-studied by w/o emulsification method followed by morphological, physical and hydrodynamic investigations. The optical microscopy (OM) and field emission scanning electron microscopy (FESEM) were applied to the morphology study of the adsorbent particles. A suitable spherical morphology and porosity have been detected for the fabricated composite beads. A suitable wet density between 1.278 and 1.895 g/mL has been detected for the composite adsorbent. The beads porosity and egg (EA) albumin effective porosity were measured for SP-KC-Fe2O3-3 with the values of about 97.83% and 75.62% respectively. In order to study the hydrodynamic behavior of KC-Fe2O3 and SP-KC-Fe2O3 composite adsorbents in expanded bed adsorption process, the residence time distribution (RTD) measurements were carried out. The results indicated that suitable physical and hydrodynamic properties of the fabricated matrices in proof the potential of their application in high flow rate magnetic field expanded bed adsorption.

Expanded Bed Adsorption of γ-Aminobutyric Acid from E. coli broth by CS16GC and IRC747 Resins.

Expanded‐bed adsorption (EBA) is an efficient downstream technology that enhances the techno‐economic potential of bio‐based industries. However, application of EBA for bulk biochemicals requires the use of industrial resins. Therefore, two cation exchangers, namely, gel‐type CS16GC and porous IRC747, were tested to purify γ‐aminobutyric acid (GABA) from unclarified E. coli fermentation broth. Experiments compared the impact of gel‐type and macroporous resin properties on the EBA process performance. As an outcome, the gel‐type resin exhibited higher GABA binding capacity of compared to that of macroporous resin. This was due to improved hydrodynamics and uniform flow distribution in the case of gel‐type resin. Further, CS16GC effectively removed ≥ 99 % of impurities and achieved ≥ 97 % GABA yield.

Rapid and efficient recovery of C-phycocyanin from highly turbid Spirulina platensis algae using stirred fluidized bed ion exchange chromatography

An efficient process for the direct extraction of CPC (Cyanobacteria-phycocyanin) from highly turbid Spirulina platensis cell homogenate that uses stirred fluidized bed adsorption (SFBA) technique has been developed. STREAMLINE DEAE (ion exchange) adsorbent was used to evaluate the optimal adsorption and elution conditions of CPC in small packed beds. When the SFBA process was employed to extract CPC from 10% (dry weight, g/mL) disrupted algae, dynamic binding efficiency, recovery yield and purification factor of CPC were determined to be 64.25%, 59.42% and 3.0, respectively, in a single step. However, as the highly concentrated feedstock was diluted to 1%, dynamic binding efficiency and recovery yield of CPC increases to 92.84% and 90.64%, respectively, with a purification factor of 2.7. A comparison of purification performance of CPC has been made between expanded bed adsorption (EBA) and stirred fluidized bed adsorption (SFBA) processes. Our experimental results showed that the productivity of CPC in SFBA process (7.52 mg/mL) was higher than that the conventional EBA process (6.71 mg/mL). Therefore, it could be concluded that the SFBA technique is technically and economically advantageous over the conventional techniques when dealing with highly turbid feedstock.

Expanded bed adsorption of albumin and immunoglobulin G from human serum onto a cation exchanger mixed mode adsorbent

Adsorption of human serum albumin (HSA) and immunoglobulin G (IgG), two most relevant proteins in blood serum were measured separately on a new mixed-mode adsorbent (MabDirect MM), especially designed for expanded bed adsorption process. Expanded bed behavior characterization by residence time distribution experiments for different columns (Streamline 50 for HSA study, Omnifit 66/20 and XK 16/20 for IgG study) are presented together with breakthrough adsorption of HSA and IgG for different conditions and compared with simulation results by a mathematical model. Regarding HSA adsorption, all four experiments were conducted at the same buffer solution (pH 5.0 without salt), and it was obtained a dynamic binding capacity of 8.9, 9.7, 7.5 and 7.0 mg·gdry−1 (24.8, 27.0, 21.0 and 19.5 mg·cm−3) at 10% of breakthrough, corresponding to a 41, 39, 38 and 30% of the saturation capacity for runs 1–4, respectively. The results from the simulation of the mathematical model fitted well with the breakthrough experiments. Elution stage was optimized by lowering flow rate and changing the buffer solution pH and NaCl concentration. Concerning IgG adsorption, for IgG feed concentration of 0.53 g·dm−3 in 20 mM citrate buffer, pH 5.0 with 0.4 M NaCl, at 2.2 cm3·min−1, it was obtained a DBC of 3.3 mg·gdry−1 (9.1 mg·cm−3) at 10% of breakthrough, representing 22% of the saturation capacity. While for a feed concentration of 0.11 g·dm−3 of IgG in the same buffer solution, at 6 cm3·min−1, it was obtained a DBC of 2.7 mg·gdry−1 (7.4 mg·cm−3) at 10% of breakthrough, representing 34% of the saturation capacity.

Mathematical modeling of the whole expanded bed adsorption process to recover and purify chitosanases from the unclarified fermentation broth of Paenibacillus ehimensis.

In this study, a general rate model was applied to the entire process of expanded bed adsorption chromatography (EBAC) for the chitosanases purification protocol from unclarified fermentation broth produced by Paenibacillus ehimensis using the anionic adsorbent Streamline® DEAE. For the experiments performed using the expanded bed, a homemade column (2.6cm×30.0cm) was specially designed. The proposed model predicted the entire EBA process adequately, giving R2 values higher than 0.85 and χ2 as low as 0.351 for the elution step. Using the validated model, a 33 factorial design was used to investigate other non-tested conditions as input. It was observed that the superficial velocity during loading and washing steps, as well as the settled bed height, has a strong positive effect on the F objective function used to evaluate the production of the purified chitosanases.

An integrated expanded bed adsorption process for lactoferrin and immunoglobulin G purification from crude sweet whey

An integrated expanded bed adsorption process was developed in this study to purify lactoferrin and immunoglobulin G (IgG) from crude sweet whey. The process used two sequential expanded beds packed with a cationic exchanger (Fastline SP) and a mixed-mode resin (Streamline Direct CST-1), respectively. Lactoferrin was isolated in the first expanded bed packed with Fastline SP, and the flow through was loaded into the second expanded bed packed with Streamline Direct CST-1 to separate IgG. Three integration strategies were compared to improve the separation efficiency, especially for the purification of IgG in the second expanded bed. The purities of IgG obtained from these three strategies were 91.9%, 83.8% and 92.4%, and the recoveries were 14.3%, 63.7% and 29.7%, respectively. By efficient integration of the two expanded beds, lactoferrin and IgG were successfully recovered from crude sweet whey with high purities and reasonable recoveries. Moreover, the stream flowed out of the integrated process was collected and separated by ultrafiltration to produce whey protein concentrate. Therefore, sweet whey resource could be fully utilized. The results demonstrated that it is possible to purify multiple proteins from untreated crude resource with a rationally designed expanded bed adsorption process.

Clarification and capture of high‐concentration refold pools for E. coli‐based therapeutics using expanded bed adsorption chromatography

Expanded bed adsorption (EBA) chromatography was investigated for clarification and capture of high-concentration refold pools of Escherichia coli-based therapeutics. Refolding of denatured inclusion bodies (IBs) at high protein concentration significantly improved product throughput; however, direct filtration of the refold materials became very challenging because of high content of protein precipitates formed during refolding. In addition, irreversible protein precipitation caused by high local concentration was encountered in packed bed capture during cation exchange chromatography elution, which limited column loading capacity and capture step productivity. In this study, the two issues are addressed in one unit operation by using EBA. Specifically, EBA can handle feed streams with significant amount of particles and precipitates, which eliminated the need for refold pool clarification through filtration. The relatively broad EBA elution profile is particularly suitable for proteins of low solubility and can effectively avoid product loss previously associated with on-column precipitation during capture. As the EBA resin (RHOBUST(®) FastLine SP IEX) used here has unique properties, it can be operated at high linear velocity (800-1,600 cm/h), while achieving a selectivity and impurity clearance largely comparable to the packed bed resin of the same ligand chemistry (SP Sepharose FF). Furthermore, the filtration of the EBA elution pool is easily manageable within facility capability. Overall, this study demonstrates that the EBA process helps debottleneck the purification of high-turbidity refold pools by removing precipitates and concurrently capturing the product, which can be applied to other E. coli-based therapeutics that also requires refolding of IBs.

One-Step Purification of Lactoferrin from Crude Sweet Whey Using Cation-Exchange Expanded Bed Adsorption

In order to purify lactoferrin from crude sweet whey in one step, an expanded bed adsorption process was proposed with cation-exchanger Fastline SP. A series of experiments were carried out to assess the possibility of this process and optimize the operating conditions. First the adsorption equilibrium and kinetics of lactoferrin with Fastline SP were measured. The results indicated that Fastline SP had a fast adsorption of lactoferrin and was suitable for high-velocity operation. Then the expansion properties, liquid mixing, and breakthrough behaviors in the expanded bed were investigated, and the expansion factor was set at 2.0. In addition, the elution condition was optimized as 0.5 M NaCl in the phosphate buffer (pH 7.0). Finally, lactoferrin was successfully recovered with a high purity of 88.5% and a reasonable recovery of 77.1% in a single step. The purification factor reached 553.

A Comparative Study of Agarose-Nickel prototype Composite Adsorbent and Commercial Streamline DEAE Adsorbent: Physical and Hydrodynamical Assessments

Expanded bed adsorption (EBA) is an integration technology for capturing target bioproducts directly from unclarified feedstock, designing and applying a good adsorbent affects its performance. In present work, a novel matrix has been developed for expanded bed adsorption process. The prepared matrix was manufactured using water-in-oil emulsification method. Desirable adsorbents tend to be of small size, high density as well as high porosity. Here, the prepared matrices had regular spherical shape, wet density of 1.95, followed logarithmic normal size distribution within the range of 50-200 µm, mean diameter of 126.4 µm and 91.93% prosily. The Richardson-Zaki equation expressed the bed expansion and operation flow rate for the prepared matrix and Streamline DEAE. In addition, the theoretical prediction of correlation parameters (U and n) was also measured. t To characterize the hydrodynamic properties in the expanded bed, the residence time distribution method was used. The physical and hydrodynamic properties of the fabricated matrix were studied and compared with those of the commercial Streamline DEAE matrix. The results indicated that the prepared matrices showed good expansion and stability in the bed and are thus suitable for expanded bed applications.

A novel method for the preparation of spherical cellulose‐tungsten carbide composite matrix with NMMO as nonderivatizing solvent

AbstractN‐methylmorpholine‐N‐oxide (NMMO) was used as the nonderivatizing solvent for dissolving cellulose, and the cellulose‐tungsten carbide composite particles were prepared with water‐in‐oil suspension and cooling regeneration. Some key factors, such as dissolution temperature and time, water content, cellulose concentration, dispersion, and cooling were optimized. The solubility of cellulose in the NMMO solution was greatly dependent on the water content, which should be controlled at the range of 11 to 15 wt %. In addition, the influences of water content of the cellulose/NMMO/water solution on the properties of composite beads were studied, including bead size, wet density, and pore properties. It was found that 13 wt % water content was most appropriate. The expansion and liquid mixing properties of composite beads in an expanded bed were also explored. The results indicated that the cellulose composite beads prepared could be used as the matrix for expanded bed adsorption processes. Compared with the traditional technology with cellulose xanthate viscose, new method based on the NMMO dissolution is more environment‐friendly, reduces the process time and shows a potential application for large scale preparation. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Expansion and hydrodynamic properties of β-cyclodextrin polymer/tungsten carbide composite matrix in an expanded bed

The expansion and hydrodynamic properties of matrix are significant for expanded bed adsorption (EBA) processes. A series of new composite matrices CroCD-TuC are studied and estimated in an expanded bed. It is found that the heavier matrix is better suited for high operation fluid velocity than the lighters. Although the Richardson–Zaki equation can well correlate the bed voidage with fluid velocity for all CroCD-TuC matrices tested, the modifications are proposed to improve the accuracy of theoretical predictions of correlation parameters, including terminal settling velocity ( U t ) and expansion index ( n). Residence time distributions (RTDs) are determined, and the Bodenstein number ( Bo) and axial dispersion coefficient ( D ax ) are employed to analyze the liquid mixing in the expanded bed. It is found for CroCD-TuC matrices, both parameters notably changed with the variation of fluid velocity and viscosity. Furthermore, D ax is an intuitive parameter estimating the bed stability on various operating conditions, and also a restriction on developing the matrix for high operation fluid velocity. The comparison of the hydrodynamic properties on different matrices reveals that CroCD-TuC 3 and CroCD-TuC 4 seem superior to other matrices in hydrodynamic properties, making them promising matrices for further use. The correlations as the functions of fluid velocity and viscosity have been established which may provide beneficial information for practical applications of CroCD-TuC matrices in EBA processes.

Mathematical modeling and simulation of inulinase adsorption in expanded bed column

A mathematical model for an expanded bed column was developed to predict breakthrough curves for inulinase adsorption on Streamline SP ion-exchange adsorbent, using a crude fermentative broth with cells as the feedstock. The kinetics and mass transfer parameters were estimated using the PSO (particle swarm optimization) heuristic algorithm. The parameters were estimated for each expansion degree (ED) using three breakthrough curves at initial inulinase concentrations of 65.6 U mL −1. In sequence, the model parameters for an ED of 2.5 were validated using the breakthrough curve at an initial concentration of 114.4 U mL −1. The applicability of the validated model in process optimization was investigated, using the model as a process simulator and experimental design methodology to optimize the column and process efficiencies. The results demonstrated the usefulness of this methodology for expanded bed adsorption processes.

Characterization and evaluation of a macroporous adsorbent for possible use in the expanded bed adsorption of flavonoids from Ginkgo biloba L.

The suitability of the use of macroporous adsorbent Amberlite XAD7HP in expanded bed adsorption processes for the isolation of flavonoids from crude extracts of Ginkgo biloba L. has been assessed. The expansion and hydrodynamic properties of expanded beds were investigated and analyzed. The bed expansion as a function of operational fluid velocity was measured and correlated with the Richardson–Zaki equation. Theoretical predictions of the correlation parameters (the terminal settling velocity u t and exponent n) were improved by modifying equations in the literature. Residence time distributions (RTDs) were studied using acetone as a tracer. Three measures of liquid phase dispersion (the height equivalent of theoretical plate, Bodenstein number and axial distribution coefficient) were investigated and compared to values previously obtained with commercial EBA adsorbents developed for protein purification. A suitable bed expansion ratio was found to be 1.25 times the settled bed height, which occurred at a corresponding flow velocity of 183 cm/h. For an initial settled bed height of 42 cm, the mean residence time of liquid in the expanded bed was around 28 min. Under these flow conditions, the axial mixing coefficient D ax was 7.54 × 10 −6 m 2/s and the Bodenstein number was 28; the number of theoretical plates ( N) was 19 and the height equivalent of a theoretical plate (HETP) was 2.77 cm. Rutin trihydrate was used as a model flavonoid for the characterization of the adsorption properties of Amberlite XAD7HP. Adsorption was observed to reach equilibrium within 3 h with 70% of the adsorption capacity being achieved within 30 min. The estimated maximum equilibrium adsorption capacity for rutin was estimated to be 43.0 mg/(g resin) when the results were fitted to Langmuir isotherms. The adsorption performance was not seriously impaired by the physical presence of G. biloba leaf powders. Assessment of the kinetics of the adsorption of rutin revealed that the rate constant for adsorption was only reduced by 15% in the presence of leaf powders at a concentration of 50 mg/mL. The results demonstrated that Amberlite XAD7HP should be suitable for expanded bed adsorption of flavonoids from crude extracts of G. biloba L.

Adsorbents for Expanded Bed Adsorption: Preparation and Functionalization

Expanded bed adsorption (EBA), a promising and practical separation technique, has been widely studied in the past two decades. The development of adsorbents for EBA process is a challenging course, with the special design and preparation according to the target molecules and specific expanded bed systems. Many types of supporting matrices for expanded bed adsorbents have been developed, and their preparation methods are being consummated gradually. These matrices are activated and then coupled with ligands to form functionalized adsorbents, including ion-exchange adsorbents, affinity adsorbents, mixed mode adsorbents, hydrophobic charge induction chromatography adsorbents and others. In this review, the preparation of the matrices for EBA process is summarized, and the coupling of ligands to the matrices to prepare functionalized adsorbents is discussed as well.

Recovery and partial purification of penicillin G acylase from E. coli homogenate and B. megaterium culture medium using an expanded bed adsorption column

The adsorption of penicillin G acylase (PGA) from B. megaterium and from Escherichia coli on a cationic resin, Streamline SP XL, was studied using both packed and expanded beds. Stability assays showed that penicillin acylases from the two sources presented high irreversible deactivation at pH 4.0 and 4.5, but remained stable at pH 4.8. Adsorption experiments performed in a packed bed (PB), in the pH range 4.8–5.8, showed highest adsorption yields at pH 4.8, for both enzymes. Using small expanded bed adsorption (EBA) columns, PGA was directly recovered and partially purified from E. coli crude extracts, E. coli homogenates, and from B. megaterium centrifuged broth in a single unit operation. Global recovery yields of 91.0, 55.0 and 7.4% and purification factors of 4.5-, 7.5- and 12.7-fold were achieved, respectively. The elution yields of penicillin acylase obtained with these cationic EBA processes when working with E. coli homogenate and B. megaterium centrifuged medium were of 100 and 52%, respectively. The comparison of adsorption capacities of E. coli penicillin acylase from crude extracts onto Streamline SP XL showed similar results for packed-bed and for expanded-bed modes. However, PGA adsorption yields for E. coli (homogenate) and B. megaterium (centrifuged medium) were substantially lower than the values obtained for E. coli crude extract, due to the competition of cell debris and other components present in the B. megaterium medium.

Chromatographic performance of macroporous cellulose–tungsten carbide composite beads as anion-exchanger for expanded bed adsorption at high fluid velocity

Macroporous cellulose–tungsten carbide composite beads was designed and prepared as an anion-exchanger for expanded bed adsorption (EBA). The wet density of composite beads was adjusted at the range of 1.2–2.4 g/ml with the control of tungsten carbide addition, and optimized for EBA at high fluid velocity. The results indicated that the wet density of composite beads could increase linearly with the increase of tungsten carbide addition, meanwhile other physical properties, such as size, porosity, specific surface area, mean pore diameter, etc., were hardly or slightly influenced. The composite beads were coupled with diethylaminoethyl (DEAE) as an anion-exchanger for EBA. The expansion characteristics in expanded bed were investigated and sensitively changed as the wet density of composite beads, corresponding to tungsten carbide addition in the preparation. The relation among the operation fluid velocity, the ratio of tungsten carbide to cellulose viscose in the preparation and the expansion factor was found, which could be used to predict the operation velocity of composite beads with varying tungsten carbide addition. The liquid mixing in expanded bed was also tested and showed good bed stability for EBA processes. With the adsorption equilibrium experiments, the saturated adsorption capacity of bovine serum albumin could reach 68.7 mg/g adsorbents (equal to 97.1 mg/ml adsorbents). The ratio of Q 10% (the dynamic adsorption at 10% breakthrough) in expanded bed to packed bed could reach more than 90% for the fluid velocity of 500 cm/h, even 77.1% for the fluid velocity as high as 900 cm/h. The chromatographic results demonstrated that the composite beads prepared are suitable for EBA applications at high fluid velocity.

Mechanistic analysis on the effects of salt concentration and pH on protein adsorption onto a mixed-mode adsorbent with cation ligand

Streamline Direct HST is a new kind of mixed-mode adsorbent with cation exchange ligand, especially developed for the expanded bed adsorption process, which can capture target protein directly from the moderate ionic strength feedstock without the need of dilution or other additives. In this study, the isotherm adsorption behaviors and the isocratic retention factors of bovine serum albumin (BSA) on Streamline Direct HST were measured, and the corresponding adsorption mechanisms were also described. The results indicated that Streamline Direct HST shows the typical property of salt-independent adsorption and the maximum binding capacity of BSA occurs near the isoelectric point of BSA. When there are some amounts of electrostatic repulsion protein–adsorbent interactions, the multilayer adsorption could be found, and high salt concentration does not favor the adsorption of protein. A patch-controlled adsorption process and an oriented adsorption model are proposed for describing the adsorption behaviors under electrostatic repulsion condition.