生物酶反应器讲座PPT.ppt

生 物 反 应 器,生物反应器这一术语出现的时间不长，但人们利用生物反应器进行有用物质生产却有着悠久的历史。 我们祖先酿制传统发酵食品时使用的容器就是最初的生物反应器。 20世纪40年代是生物反应器的开发、研制和应用获得迅速发展的阶段。 传统生物工业中使用的生物反应器称为“发酵罐”（fermenter）,生物反应器历史简介,20世纪70年代，Atkinson提出了生化反应器（biochemical reactor）一词，其含义除包括原有发酵罐外，还包括酶反应器、处理废水用反应器等。 同一时期，Ollis提出了另一术语生物反应器（biological reactor）. 20世纪80年代，生物反应器（bioreactor)一词在专业期刊与书籍中大量出现。,一、生物反应器概述,生物反应是利用生物催化剂将原料转化为有用物质的生产过程，生物反应器（biological reactor）是完成生化反应（酶促反应）的核心装置，其为生化反应提供适合的场所和最佳的反应条件，使底物最大限度地转化为产物，因此生物反应器是连接原料与产物的桥梁。,生物反应器，bioreactor是bio与reactor的组合词，是指有效利用生物反应机能的系统（或场所）。 生物反应器不仅包括传统的发酵罐、酶反应器，还包括采用固定化技术后的固定化酶或细胞反应器、动植物细胞培养用反应器和光合生物反应器等。,酶制备,原料预处理,灭菌,生物反应器,产物提纯,产品,空气,除菌,生物反应过程示意图,生物反应器设计的主要目标,产品质量高，生产成本低,评价生物反应器的主要目标 反应器生产能力的大小和产品质量的高低,生产能力（生产率）指单位时间（hr）和单位反应器体积（L）所生产的产品量（g）,生物反应器的一般要求,1.所用的生物催化剂应具有较高的比活和酶浓度（或细胞浓度） 目的为获得较高的产品转化率。 （产品转化率是指每消耗1g底物能得到产物的克数） 2.能用电脑自动检测和调控，以获得最佳的反应条件 如最适pH、温度及底物浓度,3.具有良好的传质和混合性能 传质指底物和产物在反应介质中的传递。 如底物从主体溶液向固定化载体外表面传递，然后向载体上酶分子活性部位传递；产物形成后从活性中心向载体表面传递，然后向主体溶液传递，由于固定化酶反应是固液相（非均相）状态进行，所以存在传质阻力。 传质阻力是反应器反应速度的主要限制因素，它能降低反应器的生产能力,生物反应系统中，反应物（基质）从反应液主体到生物催化剂（微生物细胞、固定化酶或细胞等）表面的传递过程对生物反应过程影响很大，特别是基质的传递速率低于生物催化剂的反应速率时，生物催化剂的催化效率将受到基质传递速率的限制 4. 应具有良好的无菌条件,生物反应器的分类,酶反应器 细胞反应器,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,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(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反应器,？ ？ ？,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） 动物细胞反应器 植物细胞反应器,二、酶反应器,1. 分批搅拌反应器（Batch stirred tank reactor,BSTR),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,Basic stirred tank reactor consists of a tank equipped with a stirring device. It will also have a heating/cooling system and baffles to ensure adequate mixing,优点：装置简单，造价低，传质阻力小，反应可迅速达到稳态 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,Disadvantage Stirred 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 addition stirred tanks can suffer from batch-to batch variations. The stirred tank is very good for small scale production of high-cost products,2. 连续流搅拌反应器（Continuous flow stirred tank reactor，CSTR) 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 Advantages It is simple to use and so is very versatile. In this kind of reactor the enzyme is either added to the solution in the tank, or an immobilised enzyme is dispersed in the reaction solution. A variation is to retain the immobilised enzyme in baskets attached to the impeller shaft, leading to low mass-transfer resistance. This kind of reactor can be used for substrate-inhibited enzymes where substrate is continuously added at a low concentration (fed-batch operation).,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 product. This is desirable for substrate-inhibited enzymes but will cause problems with product inhibited enzymes. The low substrate also reduces the effectiveness factor which can mean very inefficient use of the enzyme. One advantage of CSTRs is the ease of monitoring parameters such as temperature and pH.,Feed stream,Product stream,3. 填充床反应器(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固定化酶柱床，完成产物的形成,A packed bed reactor (PBR) the immobilized enzyme particles are held in a column and substrate is pumped 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,A PBR the enzyme at the bottom of the column is exposed to substrate whereas the enzyme at the top is exposed largely to product. This type of reactor is not well suited then for substrate inhibited enzymes Main disadvantage with PBRs is the difficulty of maintaining even 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PBR串联操作，或将PBR分成几个不同的区域，在不同进口处加入底物溶液,4. 流化床反应器（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，使固定化酶颗粒始终处于流化状态,Fluidized bed reactors are intermediate in behaviour between PBRs and CSTRs. The immobilized enzyme bed is fluidized by upward motion 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） Fluidized beds are particularly useful if a reaction utilizes or releases a gas. The gas stream can then be used to fluidize the bed 缺点： 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 difficult to scale up and their use is generally restricted to small scale high priced products,近年来为了提高传质，在固定化酶（细胞）载体内添加磁性物质，使柱床在磁场下运行,5. 连续流膜反应器 （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,In a membrane reactor the enzyme is contained within a semi-permeable membrane immersed in a stirred tank,优点：产物回收方便，酶活易保存 The principle advantage of membrane reactors is that they are easy to use and involve no enzyme immobilisation. They are often used for small scale production and applications involving multi-enzyme systems and co-factor recycle 缺点：不适合于大分子底物,膜的成本较高 The principle disadvantage is the high cost of the membranes,三、酶反应器的操作存在的问题,酶的稳定性 重金属； 不合适的pH； 混合过程中气泡使游离酶变性； 固定化酶颗粒的破碎； 酶从载体上脱落 2. 微生物的污染,Stirred tank batch reactor (STR), which contains all of the enzyme and substrates) until the conversion is complete; Batch membrane reactor (MR), where the enzyme is held within membrane tubes which allow the substrate to diffuse in and the product to diffuse out. This reactor may often be used in a semicontinuous manner, using the same enzyme solution for several batches; Packed bed reactor (PBR), also called plug -flow reactor (PFR), containing a settled bed of immobilized enzyme particles; Continuous flow stirred tank reactor (CSTR) which is a continuously operated version of (a); (e) continuous flow membrane reactor (CMR) which is a continuously operated version of (b); Fluidized bed reactor (FBR), where the flow of gas and/or substrate