1、生生 物物 反反 应应 器器酶制备酶制备原料预处理原料预处理灭菌灭菌生物反应器生物反应器产物提纯产物提纯产品产品空气空气除菌除菌生物反应器的分类生物反应器的分类 酶反应器酶反应器 细胞反细胞反应器应器 游离酶反应器固定化酶反应器游离细胞反应器固定化细胞反应器游离细胞反应器固定化细胞反应器根据使用对象的不同根据使用对象的不同以游离酶或固定化酶、固定化细胞作为生物催化剂进行酶促反应的装以游离酶或固定化酶、固定化细胞作为生物催化剂进行酶促反应的装置，称为酶反应器置，称为酶反应器(概括意义上）概括意义上）利用增殖细胞内的酶系将培养液中的成分转化为产品的装置称为细胞利用增殖细胞内的酶系将培养液中的成分转
2、化为产品的装置称为细胞反应器反应器？根据培养生物的种类，细胞反应器可以分为根据培养生物的种类，细胞反应器可以分为微生物细胞反应器（发酵罐）微生物细胞反应器（发酵罐）动物细胞反应器动物细胞反应器植物细胞反应器植物细胞反应器二、酶反应器二、酶反应器1.1.分批搅拌反应器（分批搅拌反应器（Batch stirred tank reactor,BSTR)Batch stirred tank reactor,BSTR)底物和酶一次性投入反应器，产物一次性取出；底物和酶一次性投入反应器，产物一次性取出；对于固定化酶，在反应结束后经过滤回收，转入下一批反应对于固定化酶，在反应结束后经过滤回收，转入下一批反应
3、Basic stirred tank reactor consists of a tank equipped with a Basic stirred tank reactor consists of a tank equipped with a stirring device.It will also have a heating/cooling system and stirring device.It will also have a heating/cooling system and baffles to ensure adequate mixingbaffles to ensure
4、 adequate mixing优点：装置简单，造价低，传质阻力小，反应可迅速优点：装置简单，造价低，传质阻力小，反应可迅速达到稳态达到稳态缺点：操作繁琐，酶易失活，因此在工业中该反应器缺点：操作繁琐，酶易失活，因此在工业中该反应器主要用于游离酶主要用于游离酶DisadvantageStirred tank reactor is that the tank has to be emptied and refilled at the end of the batch run.This leads to down-time and a loss of productivity.In additio
5、n stirred tanks can suffer from batch-to batch variations.The stirred tank is very good for small scale production of high-cost products2.2.连续流搅拌反应器（连续流搅拌反应器（Continuous flow stirred tank reactorContinuous flow stirred tank reactor，CSTR)CSTR)主要用于固定化的生物催化剂主要用于固定化的生物催化剂向反应器中投入固定化酶和底物溶液，不断搅拌，反应达到平衡后，再以向
6、反应器中投入固定化酶和底物溶液，不断搅拌，反应达到平衡后，再以恒定流速连续流入底物溶液，同时以相同流速输出反应液（含产物）恒定流速连续流入底物溶液，同时以相同流速输出反应液（含产物）The continuous flow stirred tank reactor(CSTR)is essentially a stirred tank with a continuous feed of substrate and an outflow of product:优点：混合良好，各部分组成均一，并与输出组分一致优点：混合良好，各部分组成均一，并与输出组分一致AdvantagesAdvantagesIt
7、is simple to use and so is very versatile.In this It is simple to use and so is very versatile.In this kind of reactor the enzyme is either added to the kind of reactor the enzyme is either added to the solution in the tank,or an immobilised enzyme is solution in the tank,or an immobilised enzyme is
8、 dispersed in the reaction solution.A variation is to dispersed in the reaction solution.A variation is to retain the immobilised enzyme in baskets attached to the retain the immobilised enzyme in baskets attached to the impeller shaft,leading to low mass-transfer resistance.impeller shaft,leading t
9、o low mass-transfer resistance.This kind of reactor can be used for substrate-inhibited This kind of reactor can be used for substrate-inhibited enzymes where substrate is continuously added at a low enzymes where substrate is continuously added at a low concentration(fed-batch operation).concentrat
10、ion(fed-batch operation).缺点：搅拌剪切力大，易破坏固定化酶的颗粒缺点：搅拌剪切力大，易破坏固定化酶的颗粒A CSTR the enzyme is subjected to low substrate and high A CSTR the enzyme is subjected to low substrate and high product.This is desirable for substrate-inhibited enzymes but product.This is desirable for substrate-inhibited enzymes b
11、ut will cause problems with product inhibited enzymes.The low will cause problems with product inhibited enzymes.The low substrate also reduces the effectiveness factor which can mean substrate also reduces the effectiveness factor which can mean very inefficient use of the enzyme.very inefficient u
12、se of the enzyme.One advantage of CSTRs is the ease of monitoring parameters such One advantage of CSTRs is the ease of monitoring parameters such as temperature and pH.as temperature and pH.FeedstreamProductstream3.3.填充床反应器填充床反应器(Packed bed Reactor,PBR)(Packed bed Reactor,PBR)又称为固定床反应器，是工业生产和科研中应用最
13、为普遍的反应器又称为固定床反应器，是工业生产和科研中应用最为普遍的反应器底物溶液以缓慢恒定的速度从反应器的底部向上通过底物溶液以缓慢恒定的速度从反应器的底部向上通过固定化酶柱床，完成产物的形成固定化酶柱床，完成产物的形成A packed bed reactor(PBR)the immobiliA packed bed reactor(PBR)the immobilized ened enzyme me particles are held in a column and substrate is particles are held in a column and substrate is p
14、umped through under plug flow conditionspumped through under plug flow conditions缺点：传质系数和传热系数相对较低，当底物溶液含有颗粒缺点：传质系数和传热系数相对较低，当底物溶液含有颗粒或粘度大时，不宜采用；不适合于产物抑制酶催化的反应或粘度大时，不宜采用；不适合于产物抑制酶催化的反应优点：高效，易操作，结构简单优点：高效，易操作，结构简单A PBR the enzyme at the bottom of the column is exposed to PBR the enzyme at the bottom o
15、f the column is exposed to substrate whereas the enzyme at the top is exposed largely to substrate whereas the enzyme at the top is exposed largely to product.This type of reactor is not well suited then for substrate product.This type of reactor is not well suited then for substrate inhibited enzym
16、esinhibited enzymes Main disadvantage with PBRs is the difficulty of maintaining even Main disadvantage with PBRs is the difficulty of maintaining even flow and constant temperature.flow and constant temperature.为降低产物的抑制引起的不良反应，一般可采用多个为降低产物的抑制引起的不良反应，一般可采用多个PBRPBR串联操作，或将串联操作，或将PBRPBR分成几个不同的区域，在不同进分成
17、几个不同的区域，在不同进口处加入底物溶液口处加入底物溶液4.4.流化床反应器（流化床反应器（Fluidized Bed Reactor,FBR)Fluidized Bed Reactor,FBR)底物溶液以足够大的流速从反应器的底部向上通过固定化酶柱床，底物溶液以足够大的流速从反应器的底部向上通过固定化酶柱床，使固定化酶颗粒始终处于流化状态使固定化酶颗粒始终处于流化状态Fluidized bed reactors are intermediate in behaviour between PBRs Fluidized bed reactors are intermediate in behav
18、iour between PBRs and CSTRs.The immobilized enzyme bed is fluidized by upward and CSTRs.The immobilized enzyme bed is fluidized by upward motion of the substrate streammotion of the substrate stream优点：传热和传质性能良好，可用于处理粘度较大和含有固体颗粒的底优点：传热和传质性能良好，可用于处理粘度较大和含有固体颗粒的底物物,同时适合于需要供给气体或排放气体的反应（即固液气三相反应）同时适合于需要供
19、给气体或排放气体的反应（即固液气三相反应）Fluidized beds are particularly useful if a reaction utilizes Fluidized beds are particularly useful if a reaction utilizes or releases a gas.The gas stream can then be used to fluidize or releases a gas.The gas stream can then be used to fluidize the bedthe bed缺点：缺点：很难进行大规模的操作，
20、仅适合小规模高价值产品的生产很难进行大规模的操作，仅适合小规模高价值产品的生产The principle disadvantage of fluidized beds is that they are The principle disadvantage of fluidized beds is that they are difficult to scale up and their use is generally restricted to difficult to scale up and their use is generally restricted to small scale
21、 high priced productssmall scale high priced products近年来为了提高传质，在固定化酶（细胞）载体内添加近年来为了提高传质，在固定化酶（细胞）载体内添加磁性物质，使柱床在磁场下运行磁性物质，使柱床在磁场下运行5.5.连续流膜反应器连续流膜反应器（Continuous flow membrane reaction,CMR)Continuous flow membrane reaction,CMR)利用半透膜将酶限制在有限的区域，底物经过扩散与酶作用利用半透膜将酶限制在有限的区域，底物经过扩散与酶作用In a membrane reactor th
22、e enzyme is contained within a In a membrane reactor the enzyme is contained within a semi-permeable membrane immersed in a stirred tanksemi-permeable membrane immersed in a stirred tank优点：产物回收方便，酶活易保存优点：产物回收方便，酶活易保存The principle advantage of membrane reactors is that they are The principle advantag
23、e of membrane reactors is that they are easy to use and involve no enzyme immobilisation.They are easy to use and involve no enzyme immobilisation.They are often used for small scale production and applications often used for small scale production and applications involving multi-enzyme systems and
24、 co-factor recycleinvolving multi-enzyme systems and co-factor recycle缺点：不适合于大分子底物缺点：不适合于大分子底物,膜的成本较高膜的成本较高The principle disadvantage is the high cost of the membranesThe principle disadvantage is the high cost of the membranes三、酶反应器的操作存在的问题三、酶反应器的操作存在的问题1.1.酶的稳定性酶的稳定性 重金属；重金属；不合适的不合适的pHpH；混合过程中气泡使游
25、离酶变性；混合过程中气泡使游离酶变性；固定化酶颗粒的破碎；固定化酶颗粒的破碎；酶从载体上脱落酶从载体上脱落2.2.微生物的污染微生物的污染a.a.Stirred tank batch reactor(STR),which contains all of the Stirred tank batch reactor(STR),which contains all of the enzyme and substrates)until the conversion is complete;enzyme and substrates)until the conversion is complete;a
26、.a.Batch membrane reactor(MR),where the enzyme is held within Batch membrane reactor(MR),where the enzyme is held within membrane tubes which allow the substrate to diffuse in and the membrane tubes which allow the substrate to diffuse in and the product to diffuse out.This reactor may often be used
27、 in a product to diffuse out.This reactor may often be used in a semicontinuous manner,using the same enzyme solution for several semicontinuous manner,using the same enzyme solution for several batches;batches;b.b.Packed bed reactor(PBR),also called plug-flow reactor(PFR),Packed bed reactor(PBR),al
28、so called plug-flow reactor(PFR),containing a settled bed of immobilized enzyme particles;containing a settled bed of immobilized enzyme particles;c.c.Continuous flow stirred tank reactor(CSTR)which is a Continuous flow stirred tank reactor(CSTR)which is a continuously operated version of(a);(e)cont
29、inuous flow continuously operated version of(a);(e)continuous flow membrane reactor(CMR)which is a continuously operated version membrane reactor(CMR)which is a continuously operated version of(b);of(b);d.d.Fluidized bed reactor(FBR),where the flow of gas and/or Fluidized bed reactor(FBR),where the
30、flow of gas and/or substrate keeps the immobilized enzyme particles in a fluidized substrate keeps the immobilized enzyme particles in a fluidized state.state.由于生物反应过程中涉及的质量传递过程问题十分复杂，由于生物反应过程中涉及的质量传递过程问题十分复杂，下面通过对生物反应过程中主要相关参数的举例，来研究下面通过对生物反应过程中主要相关参数的举例，来研究生物反应器的传递过程研究。生物反应器的传递过程研究。根据参数的性质特点，可以分为三
31、大类：物理参数、化学根据参数的性质特点，可以分为三大类：物理参数、化学参数及间接参数。参数及间接参数。1.1.物理参数主要有温度、压力、搅拌转速、通气流量、物理参数主要有温度、压力、搅拌转速、通气流量、泡沫水平以及基质、培养液的性质等。泡沫水平以及基质、培养液的性质等。2.2.化学参数主要有化学参数主要有pHpH值、溶解氧浓度、氧值、溶解氧浓度、氧 化还原电位、化还原电位、溶解溶解COCO2 2浓度、排气浓度、排气O O2 2分压、排气分压、排气COCO2 2分压等分压等 3.3.间接参数主要有摄氧率间接参数主要有摄氧率(OUR)(OUR)、二氧化碳生成率（、二氧化碳生成率（CERCER）、）
32、、呼吸商（呼吸商（RQRQ）、体积氧传递系数、氧利用率、生物热等）、体积氧传递系数、氧利用率、生物热等 这些参数可以通过传感器或其他检测系统以各种方式把这些参数可以通过传感器或其他检测系统以各种方式把非电量转化成电量变化，就能很方便地通过二次仪表显示，非电量转化成电量变化，就能很方便地通过二次仪表显示，记录或送电子计算机处理或控制。现在应用计算机来更好记录或送电子计算机处理或控制。现在应用计算机来更好的控制生物反应过程是生物反应器设计的重要方面之一的控制生物反应过程是生物反应器设计的重要方面之一 1.开发比活力和选择性高的生物催化剂占据重要地位，利用开发比活力和选择性高的生物催化剂占据重要地位
33、，利用基因工程技术改变酶的初级结构，实现生物细胞的定向改基因工程技术改变酶的初级结构，实现生物细胞的定向改造是主要途径。造是主要途径。2.2.生物反应器的性能常极大地受到热质传递能力的限制，必生物反应器的性能常极大地受到热质传递能力的限制，必须改进生物反应器中热质传递的方法和设备。须改进生物反应器中热质传递的方法和设备。3.3.生物反应器正向大型化和自动化方向发展，反应器的自动生物反应器正向大型化和自动化方向发展，反应器的自动检测和控制系统使反应器在最佳条件下操作成为可能，随检测和控制系统使反应器在最佳条件下操作成为可能，随着生物工程的日渐成熟和迅速发展，自动检测与控制系统着生物工程的日渐成熟和迅速发展，自动检测与控制系统将会发挥越来越重要作用。将会发挥越来越重要作用。
