分離純化技術(shù)是生物制藥過程的核心環(huán)節(jié)，為了生產(chǎn)高純度、高活性的生物藥物，傳統(tǒng)的分離純化技術(shù)遠(yuǎn)不能解決現(xiàn)代生物制藥企業(yè)的技術(shù)需求；由于生物藥結(jié)構(gòu)的多樣性以及監(jiān)管部門對生物藥的純度要求越來越嚴(yán)格，生物制藥對工藝的要求非常嚴(yán)謹(jǐn)苛刻，對材料的要求非常嚴(yán)格，使得生物藥的分離純化難度越來越大。因此，如何經(jīng)濟(jì)、高效的從復(fù)雜組分中濃縮、分離和純化目標(biāo)生物分子，往往是生物藥生產(chǎn)的瓶頸。
Separation and purification technologies is the core part of
pharmaceutical, biological drugs in order to produce high purity and
high activity, the traditional purification technology can not solve
technical requirements of modern biological pharmaceutical enterprises;
due to the biological diversity and structure of the drug regulatory
authorities of the purity of biological drugs increasingly stringent
requirements, requirements for bio pharmaceutical technology very strict
demanding, very strict requirements for materials, purification of more
and more difficult to separate the biological drugs. Therefore, how to
concentrate, separate and purify target biomolecules from complex
components is often the bottleneck of biological drug production.
切向流過濾也叫錯流過濾，是目前生物制藥工藝中重要的分離純化工藝。近年來，隨著部分注射劑產(chǎn)品（單克隆抗體，疫苗，重組蛋白，血液制品等）對濃度要求的不斷提高，生產(chǎn)成本和操作難度也逐漸增加。對于較大規(guī)模的料液過濾時，就要采用切向流過濾的方式，有利于降低綜合成本，使高濃度濃縮工藝的實(shí)現(xiàn)成為可能。
Tangential flow filtering, also called flow filtration, is an important
separation and purification process in biological pharmaceutical
technology at present. In recent years, as part of the injection
products (monoclonal antibodies, vaccines, recombinant proteins, blood
products, etc.) continue to increase the concentration requirements, the
production cost and operation difficulty also gradually increase. For
larger scale material filtration, tangential flow filtration is adopted,
which helps reduce the comprehensive cost and make the high
concentration process possible.
切向流過濾的原理圖。
A schematic diagram of a tangential flow filter.
切向流過濾屬于壓力過濾/膜過濾技術(shù)中的一種。在傳統(tǒng)的死端過濾技術(shù)中，濾液的流動方向與濾膜垂直，與過濾方向一致，大部分小分子透過濾膜，而大分子聚集在膜的表面，隨著時間的增加，膜面上堆積的顆粒也增加，過濾阻力增大，膜滲透速率下降。而在切向流過濾中，濾液的流動方向與濾膜平行，與過濾方向垂直，小部分小分子透過濾膜，大分子從膜的表面帶走，隨著時間的增加，膜面上堆積的顆粒物數(shù)量有限，不影響過濾的速度和效果。
Tangential flow filtration is one of the pressure filtration / membrane
filtration technology. In the traditional dead end filtration
technology, flow direction and vertical filtrate membrane, consistent
with the direction of the filter, most of the small molecules through
the membrane surface and molecular aggregation in the membrane, with the
increase of time, the accumulation of film on the surface of the
particles increases, filtration resistance increased, the membrane
permeation rate decreased. In the tangential flow filtration, the
filtrate and filter the flow direction parallel to the vertical
direction and filtering, small part of small molecules through the
membrane molecules from the membrane surface away, as time increases,
the accumulation of particles on the membrane surface of a limited
number, does not affect the speed and effect of filtering.
切向流過濾系統(tǒng)。
Tangential flow filter system.
切向流過濾技術(shù)常用于生物制品，血制品及疫苗的生產(chǎn)。美國芝加哥市的某DNA實(shí)驗(yàn)室采用切向流過濾系統(tǒng)，將金綴合抗體溶液進(jìn)行濃縮收集，濃縮后濃度達(dá)到濃縮前的20倍。
The tangential flow filtration is often used in the production of
biological products, blood products and vaccines. A DNA laboratory in
Chicago, USA, used the tangential flow filtration system to concentrate
and collect the gold conjugated antibody solution, and the concentration
reached 20 times before the concentration.
美國芝加哥市的某DNA實(shí)驗(yàn)室搭建的金綴合抗體濃縮實(shí)驗(yàn)裝置。
An experimental device for concentration of conjugated antibody was set up in a DNA laboratory in Chicago, USA.
該過濾濃縮系統(tǒng)使用了蘭格公司的蠕動泵和配套產(chǎn)品，包括BT600-2J驅(qū)動器加裝YZ2515X泵頭、Pharmed
15#軟管，來驅(qū)動濾液順利通過過濾器，并提供跨膜壓，使溶液中多余的水分子及其他小分子（無色透明）通過超濾膜，收集在錐形瓶中。而金綴合抗體（紅色），因其分子量大，無法通過超濾膜，在蠕動泵的驅(qū)動下，回流至收集瓶中。金綴合抗體濃縮系統(tǒng)在泵送濾液時，要求：
The filtration and concentration system using Lange company peristaltic
pump and ancillary products, including the BT600-2J driver with YZ2515X
pump head, Pharmed 15# hose, to drive the filtrate smoothly through the
filter, and the transmembrane pressure, the excess water molecules in
solution and other small molecules (colorless) by ultrafiltration,
collected in flasks. And the gold conjugate antibody (red), because of
its large molecular weight, can not pass through the ultrafiltration
membrane, under the drive of the peristaltic pump, reflux into the
collecting bottle. The gold conjugate antibody concentration system in
the pump filtrate requires:
保證生物分子的完整性和生物活性。
To ensure the integrity and biological activity of biomolecules.
泵送溶液流量：40 mL/min, 但隨著濃縮的進(jìn)行，溶液密度增加，需要根據(jù)壓力表的指示，降低泵的轉(zhuǎn)速和流量，以防止系統(tǒng)壓力持續(xù)增高而超過過濾器可承受的壓力。
The flow rate of pump solution is 40 mL/min, but with the concentration
increasing, the density of solution increases. It is necessary to reduce
the speed and flow of pump according to the indication of pressure
gauge, so as to prevent the pressure of the system from increasing
continuously and exceed the pressure that the filter can bear.
泵送系統(tǒng)可靠，在連續(xù)工作3-5小時內(nèi)，不會出現(xiàn)漏液問題，以減小金綴合抗體的損失。
The pump system is reliable. Within 3-5 hours of continuous work, the
problem of leakage will not appear to reduce the loss of conjugated
antibody.
蘭格公司生產(chǎn)的BT600-2J驅(qū)動器和YZ2515X泵頭。
The BT600-2J driver and the YZ2515X pump head produced by Lange company.
蘭格公司配套蠕動泵銷售的Pharmed 15#軟管。
Pharmed 15# hose sold by Langer company supporting peristaltic pump.
BT600-2J驅(qū)動器 + YZ2515X泵頭 + Pharmed 15#軟管的蠕動泵方案具有如下優(yōu)勢：
The BT600-2J driver + YZ2515X pump head + Pharmed 15# hose wriggle pump scheme has the following advantages:
蘭格的蠕動泵具有低剪切力，在泵送生物活性物質(zhì)時，可以保證生物分子的完整性和活性。
Langer's peristaltic pump has a low shear force, which can ensure the
integrity and activity of biomolecules when pumping bioactive
substances.
蘭格的蠕動泵更換軟管簡單方便，在實(shí)驗(yàn)室中，傳輸不同溶液時，僅通過簡單更換滿足衛(wèi)生等級的軟管，即可避免不同溶液之間的交叉污染。
Lange's peristaltic pump replacement hose is simple and convenient. In
laboratory, when transferring different solutions, it can avoid cross
contamination between different solutions only by simply replacing the
hose that meets the hygienic grade.
蘭格的蠕動泵方案提供1.6 - 960 ml/min的流量范圍。流量可手動調(diào)節(jié)，也可通過接收外部控制器發(fā)出的控制信號，實(shí)現(xiàn)過濾系統(tǒng)流量的自動調(diào)節(jié)，以保證系統(tǒng)壓力在允許范圍內(nèi)。
Lange's peristaltic pump scheme provides a 1.6 - 960 ml/min flow range.
The flow can be manually adjusted, and it can also automatically control
the flow of the filtration system by receiving the control signals
emitted by the external controller, so as to ensure the system pressure
is within the allowable range.
蘭格的蠕動泵的流量誤差≤±2%，經(jīng)過校正后的流量誤差可以達(dá)到±0.5%。精準(zhǔn)可控的流量，可維持切向流過濾系統(tǒng)的連續(xù)過濾，以達(dá)到預(yù)期的濃縮效果。
The error is not more than 2% peristaltic pump Lange, flow through the
error correction can be achieved after 0.5%. The accurate and
controllable flow can maintain continuous filtration of the tangential
flow filter system to achieve the desired concentration effect.
蘭格的Pharmed軟管的耐腐蝕性和耐磨性俱佳，使用壽命>10000小時，在傳輸高價值溶液時，可最大程度的降低因軟管破損而導(dǎo)致的漏液損失。
Lange's Pharmed hose has excellent corrosion resistance and abrasion
resistance, and its service life is >10000 hours. When transporting
high value solution, it can minimize the leakage loss caused by hose
breakage.
