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气密性生物安全实验室压差控制技术与策略研究
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摘要
近年来,烈性传染病的一再爆发、新型病原体的不断出现,致使包括我国在内的世界各国开始加紧建设高等级生物安全实验室。高等级生物安全实验室是从事高致病性病原微生物检测和科学研究的重要技术平台,同时也是保护实验室工作人员不被感染、外界环境不受污染的防护屏障。气密性生物安全实验室(包括ABSL-3、ABSL-4及BSL-4)是生物安全级别最高的防护实验室,所操作的病原微生物通常能引起人或动物的严重疾病,并且有极强的传染性,对感染一般没有有效的预防和治疗措施。研究显示,生物安全实验室许多常规实验操作都会产生危害性生物气溶胶,若随空气扩散至周围环境,将引发重大公共卫生事件。
     通常防止实验室内病原微生物向外界扩散的基本原理是隔离,具体隔离方式为机械密封隔离和空气负压隔离。机械密封隔离是指用密封可靠的围护结构将传染性生物因子的操作环境与外环境相隔离,为实验室的静态防护;负压隔离是指通过控制相对污染区空气压力与相对清洁区空气压力的相对负压值,实现空气定向流动,从而可有效防止被病原微生物污染的空气向污染概率低的区域及外环境扩散,为实验室的动态防护。
     BSL-4实验室对实验室围护结构气密性和压差控制都有严格的要求,但由于国内缺乏相关的研究平台,致使关于气密性生物安全实验室的机械密封隔离及负压隔离的研究较少。国内生物安全四级实验室正处在设计和建设阶段,迫切需要此方面的技术予以支持,因此有必要开展气密性生物安全实验室隔离技术的系统研究。本课题以国家生物防护装备工程技术研究中心气密性符合BSL-4实验室要求的微环境实验室为实验对象,并以空气负压控制为研究重点,开展了气密性生物安全实验室防护隔离技术的理论分析和实验研究。
     首先,开展了气密性实验室围护结构空气渗透特性的研究。根据实验测试和数据拟合建立了气密性实验室所特有的空气渗透特性方程,其流动指数b的取值其值接近1,与一般洁净室有较大区别,说明此类气密性房间缝隙内的气流流动更接近层流。根据确立的空气渗透特性方程所建立的压差衰减模型计算结果与实验室实测压差衰减结果具有很好的一致性,证明了所建立的压差衰减模型可以准确地评估实验室在不同压差情况下的空气泄漏率,为气密性实验室的压差控制提供了理论基础。
     通过对兰州兽医研究所大动物饲养室围护结构进行密封工艺改造,经实验测试,该实验室气密性可达到BSL-4实验室的标准要求。由此说明,通过加强围护结构密封工艺,选用合适的气密防护设备,我国高等级生物安全实验室围护结构的气密性指标能够达到GB19489-2008规定的要求。
     BSL-4实验室的围护结构漏风量极低,致使送、排风量的微量变化即可引起气密性实验室压差剧烈波动,这一特性直接决定了压差控制方式及控制装置的选择。通过建立实验室压差控制数学模型,分析了房间围护结构气密性以及管路工况对压差控制的影响;同时,经过研究可以确定,气密性实验室的压差控制并不是通过控制送风量与排风量的差值来实现的,而是通过改变风量调节阀的阻抗实现的。
     通过对定风量控制方式进行理论分析和实验研究,结果表明,无论使用何种风量调节阀进行定风量控制,均难以适用于气密性生物安全实验室的压差控制。因此,气密性实验室的压差控制必须采用变风量闭环控制方式,而闭环控制算法在较大程度上决定了控制效果。
     通过对气密性生物安全实验室压差控制原理进行分析,使用MATLAB模拟软件中的Simulink工具建立了变风量压差闭环控制的数学模型。通过仿真实验,分别研究了常规PID的三个参数Kp、Ki、Kd对压差的控制作用,并分析了压差传感器延时及风量调节阀运行速度对压差控制的影响,为进行优化闭环控制提供了数据基础。
     由于常规PID只能通过一组参数对压差进行调节,难以保证同时具有良好稳定性及快速响应性,为此开展了智能模糊PID控制算法的研究。建立了以压差的偏差e与偏差变化率ec为输入量,以PID三个控制参数为输出量的模糊PID控制模型,其可通过实时监控压差运行参数,根据压差运行情况依据所建立的模糊规则在线整定PID的控制参数。仿真结果表明,模糊PID控制使压差控制系统在具有良好稳定性的同时,进一步提高了响应性及抗扰动性能,相比常规PID控制,其更适合于气密性实验室的压差控制。
     为验证常规PID控制与模糊PID控制的实际控制效果,开展了气密性实验室压差闭环控制的实验研究。通过建立微环境实验室的压差闭环控制系统,以常规PID控制为基础,实现了基于PLC的模糊PID压差控制。实验结果表明,模糊PID控制具有更好的稳定性和鲁棒性,其控制品质明显高于传统的常规PID控制性能指标。
     实验室在正常运行时会出现各种扰动,为了更好地应对扰动,开展了抗扰动控制研究。在智能控制基础上,通过对扰动进行识别分类,建立了压差扰动诊断系统,并采用混合控制策略主动应对扰动。经实验证明,该控制策略可有效控制较大扰动所产生的不利影响,保证压差平稳过渡,在很大程度上提高实验室压差的稳定性。
     开展了人为附加漏风控制的技术策略研究。经实验研究,在不降低气密性实验室静态防护性能前提下,该控制策略不但可有效降低气密性实验室对风量波动的敏感性,同时可有效降低开关门对气密性实验室压差的干扰,并可保证开门的定向流。在气密性生物安全实验室的压差控制方面具有重要的实际应用价值,值得进一步探索和完善。
     同时,研究了双调节阀粗精控制技术,即采用一大一小两支变风量调节阀进行组合控制,经过实验研究表明,该控制技术确实可以降低气密性实验室正常运行时压差的波动,适用于风量需求高的实验室。但是,在实际应用时,该控制技术需要解决双阀门如何配合调节的问题。
     综上所述,本课题对气密性生物安全实验室的压差控制进行了系统理论分析与实验研究,其研究成果将为我国气密性生物安全实验室的生物安全建设提供技术参考,填补国内在气密性实验室压差控制研究方面的空白。
In recent years, the repeated outbreaks of deadly infectious diseases and thecontinual emergence of new pathogens caused that the countries of the world,including China, began to step up the construction of high-level biosafety laboratories.The high-level biosafety laboratory is not only the important technology platformengaged in of the highly pathogenic microbiological testing and scientific research,but also the containment barrier to protect laboratory workers from being infected andthe outside environment from pollution. Airtight biosafety laboratory (includingABSL-3、ABSL-4and BSL-4) is the high-level biosfety containment laboratory, thepathogenic microorganism operated can causes severe human disease and is a serioushazard to employees, is likely to spread to the community and there is usually noeffective prophylaxis or treatment available. Studies have shown that many laboratoryprocedures may produce harmful bio-aerosols. If bio-aerosols spread to thesurrounding environment, it will lead to serious public health events.
     Generally, the basic principle to prevent the leakage of the pathogenicmicroorganism from laboratory is isolation. And the specific isolation methods aremechanical seal isolation and air negative pressure isolation. The mechanical sealisolation refers to isolate the infectious biological factors operating environment withreliable tightness building envelope from the external environment, which is the staticcontainment of the laboratory; the negative pressure isolation refers to achieve thedirectional air flow through the control of the air difference pressures of the relativecontaminated area and the relative clean area to prevent effectively the air polluted bythe pathogenic microorganism from diffusing to the area with lower potentialcontaminated and the external environment, which is the dynamic containment of thelaboratory.
     The BSL-4laboratory has strict requirements to the air tightness of the buildingenvelope and differential pressure control of the laboratory. However, due to the lackof relevant platforms in our country, there is less research on the mechanical sealisolation and air negative pressure isolation of the airtight biosafety laboratory. The BSL-4laboratories in our country are under construction now, which is pressed forthe relevant technical support. Therefore, it is necessary to carry out the systematicresearch on the airtight laboratory isolation techniques. The laboratory of NationalProtection Equipment Center (NPEC) meeting the requirements of the air tightness ofBSL-4laboratory was taken as the experimental subject to carry out the theoreticalanalysis and experiment study on the protection and isolation techniques of airtightlaboratory with the air negative pressure control as the research emphasis.
     First of all, the research on air permeability of building envelope of airtightlaboratory was carried out. And the specific air permeability equation for airtightlaboratory was established based on the experimental measurement and the datafitting. The value of the flow index b is close to1, which suggests that the air flow ofthe room cracks of this kind of airtight room is closer to the laminar flow. That makesa big difference with that of the ordinary clean room. The computation results of thepressure decay model established on the basis of air permeability equation is inconsistent with the measured pressure decay result of the laboratory, which provesthat the established pressure decay model can estimate accurately the air leakage rateof the laboratory under different pressures. That provides the theoretical basis for thedifferential pressure control of the airtight laboratory.
     After sealing technology modification the tightness of one large animal room inLanzhou Veterinary Research Institute, the test results show that the air tightness ofthe laboratory can meet the requirements of the Standard for BSL-4laboratory. It isshown that with the strength of the sealing technology and selection of suitableairtight protective equipments, the tightness of containment enclosure of high-levelbiosafety laboratory in our country can completely meet the requirements of standardGB19489-2008.
     The air leakage of the BSL-4laboratory building envelope is very low, so tinychanges of the air input and output will cause fluctuation of the airtight laboratorydifferential pressure. This feature determines directly the selection of the differentialpressure control method and the control device. Through the establishment of themathematical model of laboratory differential pressure control, the influence of the airtightness of the building envelope and pipeline condition on the differential pressurecontrol was analyzed; the results show that the differential pressure control of theairtight laboratory is not achieved through controlling the differential air volumebetween the air input and output but through changing the volume damper impedance.
     The constant air volume control method was studied by theoretical analysis andexperiment, the result shows that any kind of volume damper used for constant airvolume control is not suitable for the differential pressure control of the airtightlaboratory. Therefore, the variable air volume (VAV) closed-loop control must beadopted for the differential pressure control of the airtight laboratory. And theclosed-loop control algorithm determines the control effect.
     The differential pressure control principle of the airtight laboratory was analyzed,and the mathematical model of the VAV differential pressure closed-loop control wasestablished by the Simulink tool of the MATLAB simulation software. Through thesimulation experiment, the control effect of the three parameters Kp, Ki,, Kdofconventional PID on the differential pressure were studied and the influence ofdifferential pressure transducer delay and volume damper operating speed ondifferential pressure control was analyzed, which provide data basis for theclosed-loop control optimization.
     Due to that the conventional PID only can regulate the differential pressurethrough one pair of parameters, which can hardly guarantee the good stability andrapid responsiveness at the same time. Therefore, the study on the intelligent fuzzyPID control algorithm was carried out. And the fuzzy PID control model wasestablished, and the pressure deviation e and deviation change rate ec were taken asthe input variable and the three control parameters of PID as output variable. Thismodel can set the PID control parameter on line according to the differential pressureoperating conditions and the established fuzzy rule by the real time monitoring overthe differential pressure operating parameter. And the simulation result shows that thefuzzy PID control can further improves the responsiveness and the disturbancerejection performance while making the differential pressure control system havegood stability. Compared with the conventional PID control, it is more suitable for thedifferential pressure control of the airtight laboratory.
     In order to verify the actual control effect of the conventional PID control andthe fuzzy PID control, the experimental study on differential pressure closed-loopcontrol of the airtight laboratory was carried out. Through the establishment of thedifferential pressure closed-loop system of the Micro environmental laboratory and onthe basis of the conventional PID control, the fuzzy PID differential pressure controlbased on PLC was achieved. The experimental result shows that the fuzzy PID controlhas better stability and robustness and the control quality of which is obviously higher than that of the conventional PID control.
     There will be various disturbances during the normal operation of the laboratory.In order to handle the disturbances better, the disturbance-resistant control study wascarried out. On the basis of intelligent control, the differential pressure disturbancediagnostic system was established through the disturbances classification, and hybridcontrol strategy was applied to actively deal with the disturbances. The experimentresults prove that this control strategy can control effectively the adverse effectproduced by large disturbances and guarantee the smooth transition of the differentialpressure to improve the stability of differential pressure of the laboratory.
     The technology strategy of man-made additional air leakage control was putforward and studied. The experimental study shows that under the premise of notreducing the static protection performance of the airtight laboratory, this controlstrategy not only can reduce effectively the sensibility of airtight laboratory towardthe air volume fluctuation, but also can effectively reduce the opening and shuttingdoor’s disturbance toward the differential pressure of airtight laboratory at the sametime and guarantee the directional airflow when open the door. This technologystrategy has important practical application value in terms of differential pressurecontrol of airtight biosafety laboratory and deserves the further study and completion.
     At the same time, the double control valve with coarse and fine control techniquewas also studied: carry out the composite control by adopting one large and one smallVAV control valves. The study shows that this technique indeed can reduce thedifferential pressure fluctuation in the normal operation of the laboratory. And it canbe applied to the laboratory with high air volume demand. However, the coordinationand regulation of the two valves need to be solved in the practical application of thiscontrol technique.
     In conclusion, this research conducted a systematic theory analysis andexperiment study on the differential pressure control of airtight laboratory. Theresearch achievement will provide the technical reference for the safe construction ofthe airtight laboratories and fill the gap in the study on differential pressure control ofairtight biosafety laboratory in our country.
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