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CN1259409C - A magnetic bioreactor - Google Patents

A magnetic bioreactor Download PDF

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CN1259409C
CN1259409C CN 200310100483 CN200310100483A CN1259409C CN 1259409 C CN1259409 C CN 1259409C CN 200310100483 CN200310100483 CN 200310100483 CN 200310100483 A CN200310100483 A CN 200310100483A CN 1259409 C CN1259409 C CN 1259409C
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permanent magnet
reaction chamber
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steel plate
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CN1609185A (en
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阳承利
刘会洲
官月平
邢建民
安振涛
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Institute of Process Engineering of CAS
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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Abstract

本发明涉及的磁性生物反应器,包括:反应室,反应室底端安装磁颗粒进口管、生物液进口管和生物反应液排放管,上端安装循环料出口管;垂向安装于反应室中心处的中心轴上横向固定安装有呈间隔分布的多层丝网介质板;中心轴上端固定一钢板,钢板上方设一永磁铁,靠近永磁铁上表面处设有一由电机驱动而旋转的偏心轮,电机驱动偏心轮旋转,进而带动永磁铁做与钢板接触及分离相间的上下往复振动;其往复振动将磁性传递到丝网介质板,丝网介质板获得间断式磁性,磁性颗粒不断吸附在丝网介质上,而又不断地分散悬浮在反应室中,从而目标生物分子能与磁性颗粒有较大的接触表面积和较长的停留时间,提高了磁性颗粒的吸附效率,且结构简单,操作方便。

Figure 200310100483

The magnetic bioreactor involved in the present invention includes: a reaction chamber, a magnetic particle inlet pipe, a biological liquid inlet pipe and a biological reaction liquid discharge pipe are installed at the bottom of the reaction chamber, and a circulating material outlet pipe is installed at the upper end; vertically installed at the center of the reaction chamber The central axis of the center shaft is fixed with multi-layer wire mesh medium plates distributed at intervals horizontally; a steel plate is fixed on the upper end of the central axis, a permanent magnet is arranged above the steel plate, and an eccentric wheel driven by a motor is installed near the upper surface of the permanent magnet. The motor drives the eccentric wheel to rotate, and then drives the permanent magnet to reciprocate up and down between the contact with the steel plate and the separation phase; its reciprocating vibration transmits the magnetism to the wire mesh medium plate, and the wire mesh medium plate obtains intermittent magnetism, and the magnetic particles are continuously adsorbed on the wire mesh On the medium, and continuously dispersed and suspended in the reaction chamber, the target biomolecules can have a larger contact surface area and a longer residence time with the magnetic particles, which improves the adsorption efficiency of the magnetic particles, and has a simple structure and is easy to operate.

Figure 200310100483

Description

一种磁性生物反应器A magnetic bioreactor

技术领域technical field

本发明涉及生物反应装置,特别涉及一种永磁场下的磁性生物反应器。The invention relates to a bioreactor, in particular to a magnetic bioreactor under a permanent magnetic field.

背景技术Background technique

近年来,磁分离技术在化工、冶金、环保、生物工程和生物医学工程等领域中应用日益广泛。特别是把有磁性标记的生物分子或负载有生物分子的磁性颗粒从生物产品中分离出来,磁分离技术展现出独特的优势,是生化分离发展的方向。In recent years, magnetic separation technology has been widely used in chemical industry, metallurgy, environmental protection, bioengineering and biomedical engineering and other fields. Especially for the separation of magnetically labeled biomolecules or magnetic particles loaded with biomolecules from biological products, magnetic separation technology shows unique advantages and is the development direction of biochemical separation.

磁性反应器是磁性分离过程的核心部分,如何捕获细小的磁性颗粒和如何提高磁性颗粒对目标生物分子的吸附率是关键。提高背景磁场可以提高对细小磁性颗粒的捕获能力,在目前的磁分离装置中的背景磁场逐渐从电磁磁场向永磁磁场发展。关于磁性反应器和磁性分离装置(参见Journal of Chromatography A,Vol.690:1-8,1995),该磁稳定床反应装置的结构为:包括一位于电磁磁场中的反应容器,反应容器内设置多层吸附床,磁性颗粒在吸附床层中进行吸附反应时,由于目标生物分子与磁性颗粒接触面积小和停留时间较短,其吸附反应相当弱,很多目标生物分子还未来得及与磁性颗粒吸附反应,就已进入了下一步操作中,影响了磁性颗粒的利用率和吸附效率。同时该反应器采用的是电磁铁作为背景磁场,由于发热等原因很难在床内产生较高的磁场强度,导致吸附效率下降。因此,如何提高目标生物分子与磁性颗粒的接触面积和停留时间是待解决的关键问题。The magnetic reactor is the core part of the magnetic separation process, how to capture the fine magnetic particles and how to improve the adsorption rate of the magnetic particles to the target biomolecules is the key. Increasing the background magnetic field can improve the ability to capture fine magnetic particles. The background magnetic field in the current magnetic separation device gradually develops from an electromagnetic field to a permanent magnetic field. Regarding the magnetic reactor and the magnetic separation device (see Journal of Chromatography A, Vol.690: 1-8, 1995), the structure of the magnetically stabilized bed reaction device is as follows: it includes a reaction vessel located in the electromagnetic field, and the reaction vessel is set Multi-layer adsorption bed, when the magnetic particles undergo adsorption reaction in the adsorption bed layer, due to the small contact area between the target biomolecules and the magnetic particles and the short residence time, the adsorption reaction is quite weak, and many target biomolecules have not yet had time to adsorb with the magnetic particles. The reaction has already entered the next step of operation, which affects the utilization rate and adsorption efficiency of magnetic particles. At the same time, the reactor uses an electromagnet as the background magnetic field, and it is difficult to generate a high magnetic field strength in the bed due to heating and other reasons, resulting in a decrease in adsorption efficiency. Therefore, how to improve the contact area and residence time of target biomolecules and magnetic particles is a key problem to be solved.

发明内容Contents of the invention

本发明的目的在于针对现有磁性分离反应器存在的诸多缺陷,提供了一种结构简单且在永磁场下的磁性生物反应器。The object of the present invention is to provide a magnetic bioreactor with a simple structure and under permanent magnetic field, aiming at many defects existing in the existing magnetic separation reactor.

本发明的技术方案如下:Technical scheme of the present invention is as follows:

本发明提供的磁性生物反应器,包括:The magnetic bioreactor provided by the invention comprises:

一反应室,所述反应室的底端安装有磁颗粒进口管、生物液进口管和生物反应液排放管,所述反应室的上端室壁上安装有循环料出口管;A reaction chamber, the bottom of the reaction chamber is equipped with a magnetic particle inlet pipe, a biological liquid inlet pipe and a biological reaction liquid discharge pipe, and a circulating material outlet pipe is installed on the upper end of the reaction chamber;

一垂向安装于反应室中心处的中心轴;以及,a central shaft mounted vertically at the center of the reaction chamber; and,

横向固定安装在中心轴上呈间隔分布的多层丝网介质板;The multi-layer wire mesh medium boards are horizontally fixed and installed at intervals on the central axis;

所述中心轴的上端固定一钢板,钢板上方设置一永磁铁,靠近永磁铁上表面处设有一由电机驱动而旋转的偏心轮,电机驱动偏心轮旋转,进而带动永磁铁做与钢板接触及分离相间的上下往复振动;A steel plate is fixed on the upper end of the central shaft, a permanent magnet is set above the steel plate, and an eccentric wheel driven by a motor to rotate is set near the upper surface of the permanent magnet. The motor drives the eccentric wheel to rotate, and then drives the permanent magnet to contact and separate from the steel plate Up and down reciprocating vibration between phases;

所述的永磁铁的磁场为600-4600奥斯特;The magnetic field of the permanent magnet is 600-4600 Oersted;

所述永磁铁的上下往复振动的波形为正弦波或其它波形;The waveform of the up and down reciprocating vibration of the permanent magnet is a sine wave or other waveforms;

所述的丝网介质板为纯铁丝网介质板,其孔径为50μm-100μm;The wire mesh medium plate is a pure wire mesh medium plate with an aperture of 50 μm-100 μm;

所述的中心轴为纯铁轴;所述的钢板横截面面积与永磁铁横截面面积大致相等。The central axis is a pure iron axis; the cross-sectional area of the steel plate is approximately equal to the cross-sectional area of the permanent magnet.

本发明的磁性生物反应器,用永磁场替代电磁场,永磁铁由偏心轮带动做上下往复振动,振动的振幅及频率可以调节。当永磁铁向下振动时,永磁铁与中心轴连接的钢板相接触,将磁性传递到中心轴,再到丝网介质板,磁性颗粒将立即被吸附到网状介质板上;当永磁铁向上运动离开中心轴连接的钢板时,丝网介质板的磁性立即消失,磁性颗粒离开丝网介质板而分散悬浮在反应室中。永磁铁的上下往复运动,使磁性颗粒不断地聚集和分散悬浮在反应室中。这样磁性颗粒能与目标生物分子有更大表面积的接触,具有较长的停留时间,磁吸附率大大提高。而以往的磁稳定床反应器是在外加磁场作用下,使磁性颗粒固定聚集在反应室中,由于长时间的磁化,颗粒会团聚,导致目标生物分子与磁性颗粒的接触面积减小,停留时间变短,磁性颗粒的吸附率低。本发明采用永磁铁上下往复运动赋予丝网介质板间断式的磁性,可使磁性颗粒悬浮在反应室中与目标生物分子有较大的接触面积和较长的接触时间,解决了现有技术中的磁稳定床反应器使磁性颗粒团聚的问题,提高了磁性颗粒的吸附率。The magnetic bioreactor of the present invention uses a permanent magnetic field instead of an electromagnetic field, and the permanent magnet is driven by an eccentric wheel to reciprocate up and down, and the amplitude and frequency of the vibration can be adjusted. When the permanent magnet vibrates downward, the permanent magnet is in contact with the steel plate connected to the central axis, and the magnetism is transmitted to the central axis, and then to the mesh medium plate, and the magnetic particles will be immediately adsorbed to the mesh medium plate; when the permanent magnet is upward When moving away from the steel plate connected by the central axis, the magnetism of the wire mesh medium plate disappears immediately, and the magnetic particles leave the wire mesh medium plate and disperse and suspend in the reaction chamber. The up and down reciprocating motion of the permanent magnet makes the magnetic particles continuously gather, disperse and suspend in the reaction chamber. In this way, the magnetic particles can have a larger surface area contact with the target biomolecules, have a longer residence time, and greatly increase the magnetic adsorption rate. However, in the previous magnetically stabilized bed reactor, the magnetic particles are fixed and gathered in the reaction chamber under the action of an external magnetic field. Due to long-term magnetization, the particles will agglomerate, resulting in the reduction of the contact area between the target biomolecules and the magnetic particles, and the residence time shortened, the adsorption rate of magnetic particles is low. The invention adopts the up and down reciprocating motion of the permanent magnet to endow the wire mesh medium plate with discontinuous magnetism, so that the magnetic particles can be suspended in the reaction chamber and have a larger contact area and longer contact time with the target biomolecules, which solves the problems in the prior art. The problem of agglomeration of magnetic particles in the magnetically stabilized bed reactor improves the adsorption rate of magnetic particles.

本发明具有以下特点:The present invention has the following characteristics:

(1)使用永磁铁,具有很高的背景磁场。(1) Use permanent magnets, which have a high background magnetic field.

(2)永磁场通过中心轴将磁性传递到丝网介质板上,利用了磁性的传递原理。(2) The permanent magnetic field transmits the magnetism to the wire mesh medium plate through the central axis, utilizing the principle of magnetic transmission.

(3)永磁场的上下往复振动,使丝网介质板具有间断式的磁性。(3) The up and down reciprocating vibration of the permanent magnetic field makes the wire mesh dielectric plate have intermittent magnetism.

(4)磁性颗粒可长时间的分散悬浮在反应室中。(4) The magnetic particles can be dispersed and suspended in the reaction chamber for a long time.

(5)磁性颗粒对目标生物分子具有较高的吸附率。(5) Magnetic particles have a high adsorption rate for target biomolecules.

(6)调节永磁铁的振动频率丝网介质板可获得不同频率的磁性。(6) Adjusting the vibration frequency of the permanent magnet The wire mesh dielectric plate can obtain magnetism of different frequencies.

(7)反应器的结构简单,操作方便。(7) The structure of the reactor is simple and the operation is convenient.

附图说明:Description of drawings:

图1为本发明的结构示意图;Fig. 1 is a structural representation of the present invention;

图2为永磁铁与钢板接触时,磁性颗粒的工作状态示意图;Figure 2 is a schematic diagram of the working state of the magnetic particles when the permanent magnet is in contact with the steel plate;

图3为永磁铁离开钢板时,磁性颗粒的工作状态示意图;Fig. 3 is a schematic diagram of the working state of the magnetic particles when the permanent magnet leaves the steel plate;

其中:反应室1            永磁铁2                钢板3Among them: reaction chamber 1 permanent magnet 2 steel plate 3

      中心轴4            丝网介质板5            磁颗粒进口管6     Central axis 4                                                                                                                      ,

      生物液进口管7      生物反应液排放管8      循环料出口管9Biological liquid inlet pipe 7 Biological reaction liquid discharge pipe 8 Circulating material outlet pipe 9

具体实施方式Detailed ways

下面结合附图及实施例进一步描述本发明:Further describe the present invention below in conjunction with accompanying drawing and embodiment:

实施例1Example 1

如图1所示,本发明的永磁场下的磁性生物反应器,在反应室1内由多个丝网介质板5与中心轴4连接,中心轴上端连接一钢板3,在钢板3正上方安装一永磁铁2,并与钢板3保持一定距离,永磁铁2由一偏心轮带动,使永磁铁2做上下往复振动。As shown in Figure 1, the magnetic bioreactor under the permanent magnetic field of the present invention is connected with the central axis 4 by a plurality of wire mesh medium plates 5 in the reaction chamber 1, and a steel plate 3 is connected to the upper end of the central axis, directly above the steel plate 3 Install a permanent magnet 2 and keep a certain distance from the steel plate 3. The permanent magnet 2 is driven by an eccentric wheel to make the permanent magnet 2 reciprocate up and down.

实施例2Example 2

下面结合图2、图3具体说明本发明的工作原理:偏心轮(图中未示)带动永磁铁2不断地做上下往复振动,当永磁铁2向下振动时,永磁铁2与钢板3相接触,将磁性传递到中心轴4,然后再将磁性传到丝网介质板5,反应室1中的表面带有亲核配基的磁性颗粒立即被吸附到丝网介质板5上;当永磁铁2向上运动离开中心轴4连接的钢板3时,丝网介质板5的磁性立即消失,磁性颗粒便离开丝网介质板5而分散悬浮在反应室1中,这样,目标生物分子与磁性颗粒有较大表面积的接触,磁性颗粒吸附目标生物分子的量将大大增加。由于永磁铁2不断地上下往复振动,丝网介质板5也相应地获得了间断式磁性,从而使磁性颗粒不断地吸附在丝网介质板5上,而又不断地分散悬浮在反应室中。如此循环操作,目标生物分子便能与磁性颗粒有较大的接触表面积和较长的停留时间,提高了磁性颗粒的吸附效率。Below in conjunction with Fig. 2, Fig. 3 specifically illustrate the working principle of the present invention: the eccentric wheel (not shown in the figure) drives the permanent magnet 2 to continuously reciprocate up and down, and when the permanent magnet 2 vibrates downward, the permanent magnet 2 is in phase with the steel plate 3 contact, the magnetism is transferred to the central axis 4, and then the magnetism is passed to the silk mesh medium plate 5, and the magnetic particles with nucleophilic ligands on the surface in the reaction chamber 1 are immediately adsorbed on the silk mesh medium plate 5; When the magnet 2 moves upwards away from the steel plate 3 connected to the central axis 4, the magnetism of the wire mesh dielectric plate 5 disappears immediately, and the magnetic particles leave the wire mesh dielectric plate 5 and are dispersed and suspended in the reaction chamber 1. In this way, the target biomolecules and the magnetic particles With a larger surface area in contact, the amount of target biomolecules adsorbed by the magnetic particles will be greatly increased. Since the permanent magnet 2 continuously vibrates up and down, the wire mesh dielectric plate 5 also obtains discontinuous magnetism correspondingly, so that the magnetic particles are continuously adsorbed on the wire mesh dielectric plate 5 and are continuously dispersed and suspended in the reaction chamber. Such a cyclical operation allows the target biomolecules to have a larger contact surface area and a longer residence time with the magnetic particles, which improves the adsorption efficiency of the magnetic particles.

Claims (5)

1、一种磁性生物反应器,包括:1. A magnetic bioreactor comprising: 一反应室,所述反应室的底端安装有磁颗粒进口管、生物液进口管和生物反应液排放管,所述反应室的上端室壁上安装有循环料出口管;A reaction chamber, the bottom of the reaction chamber is equipped with a magnetic particle inlet pipe, a biological liquid inlet pipe and a biological reaction liquid discharge pipe, and a circulating material outlet pipe is installed on the upper end of the reaction chamber; 一垂向安装于反应室中心处的中心轴;以及a central shaft mounted vertically at the center of the reaction chamber; and 横向固定安装在中心轴上呈间隔分布的多层丝网介质板;The multi-layer wire mesh medium boards are horizontally fixed and installed at intervals on the central axis; 所述中心轴的上端固定一钢板,钢板上方设置一永磁铁,靠近永磁铁上表面处设有一由电机驱动而旋转的偏心轮,电机驱动偏心轮旋转,进而带动永磁铁做与钢板接触及分离相间的上下往复振动。A steel plate is fixed on the upper end of the central shaft, a permanent magnet is set above the steel plate, and an eccentric wheel driven by a motor to rotate is set near the upper surface of the permanent magnet. The motor drives the eccentric wheel to rotate, and then drives the permanent magnet to contact and separate from the steel plate Alternate up and down reciprocating vibration. 2、按权利要求1所述的磁性生物反应器,其特征在于,所述的永磁铁的磁场为600-4600奥斯特。2. The magnetic bioreactor according to claim 1, wherein the magnetic field of the permanent magnet is 600-4600 Oersted. 3、按权利要求1所述的磁性生物反应器,其特征在于,所述的永磁铁的上下往复振动的波形为正弦波。3. The magnetic bioreactor according to claim 1, wherein the waveform of the up and down reciprocating vibration of the permanent magnet is a sine wave. 4、按权利要求1所述的磁性生物反应器,其特征在于,所述的丝网介质板为纯铁丝网介质板,其孔径为50μm-100μm。4. The magnetic bioreactor according to claim 1, wherein the wire mesh medium plate is a pure wire mesh medium plate with a pore size of 50 μm-100 μm. 5、按权利要求1所述的磁性生物反应器,其特征在于,所述的中心轴为纯铁轴。5. The magnetic bioreactor according to claim 1, wherein said central axis is a pure iron axis.
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