分子智能学 使徒（宗慰）1，2，3，4
1.红河卫生职业学院（2015-）
2.重庆医科大学附属第一医院（2013-2014）
3.中国科学院昆明动物研究所（2010-2013）
4.中山大学（2004-2008）
通信地址：云南省红河州蒙自市杏林路杏林苑小区 邮编：661199 电话：18213471593
目的：尝试启发一种思路，来帮助后疫情时代防控体系的优化。系统构建到一定规模后，预期可以回答病原微生物从哪里来，通过系统布设前置于疫苗的防线，提供预警信息，利于早期对传染源进行干预。
方法：我们需要拓宽思路，投入合适的资源，以合适的速度，研发出基于核酸测序的病原微生物自动监测装备，合理配布，借助物联网（人联网）、大数据等技术逐渐组网建库，形成新一代的微生物防御体系，破解病原微生物隐身技能，实现对病原微生物的体外精准监测。
目前我们可以通过视频监控系统实现安防预警目的，微生物的自动监测与预警，原理上是相同的。
下面阐述几个点：广谱性、分辨率、自动化、少维护、联网化、智能化、可回溯、双轨制、拓扑配布、便携性或可搭载性。
广谱性：目前主流的检测手段是特异性检测，不能灵活应对病原微生物的变异。为实现广谱性，形态学观察明显不如测序在物种分辨上有优势，摩尔定律会逐渐驱散测序在经济方面的劣势。牛津纳米孔的MinION可能是最接近设想的测序仪主机，但要迭代成可持续自动采样分析的监测设备，核酸提取试剂盒的替代、核酸穿孔引导接头（马达蛋白）的再利用是主要的两个难题。
分辨率：取决于核酸物理提取技术研发达到的水平，监测用测序设备的参数配置，如读长、投入使用的纳米孔与总核酸拷贝数比、采样周期、样本内再采样率等。一些依赖本地算力的技术如ReadUntil技术，可以帮助提升效率。
自动化：不同样本（气体、液体、固体表面）的采样自动化，吸尘器及其不同吸头是一个很好的参照。
少维护：试剂盒提取转型为物理等免耗材提取。笔者估计最主要的易耗部件可能是纳米孔+核酸引导复合体膜。
联网化、智能化、可回溯：跨领域合作，实现新异信号自动处理、多设备校准和云端报警，参考手机计步及运动轨迹记录功能。
双轨制：初代的性能决定适用场景，后期技术迭代可能实现监测与诊断并轨。
拓扑配布：数学建模指导下，人流密集区域，人禽、人兽交界区域。
可搭载性：跨领域合作，单人车系统（个人居行数据终端及其云端系统）被成功启蒙兼容取代现有个人手机系统，拓扑配布方面，跟人布控最经济。通过微调，也可以使测序设备用于人的感染病原体鉴别、基因组测序与自身新发变异监测。如果单人车系统比微生物监测设备早实现，还可以给后者早期难以逾越的试剂耗材方面，提供车辆来源的可能性。单人车系统除外作为搭载航母，还可以共享算力、GPS定位、无线通信组网、轮胎源离心设备、气体采样仓等资源。同时，单人车比口罩或防毒面具更舒适、适合长期使用，其他车载传感器则提升流调效率。
Upgrade MinION to Automatic Monitor Net for the Pathogens Invasion
Apostle Moligence（Wei Zong）1,2,3,4
1. Honghe Health Vocational College (2015-)
2. The First Affiliated Hospital of Chongqing Medical University (2013-2014)
3. Kunming Institute of Zoology, Chinese Academy of Sciences (2010-2013)
4. Sun Yat-sen University (2004-2008)
Purpose: Try to inspire an idea to help optimize the prevention system in the post-epidemic era. When built to a certain scale, the system could answer where the pathogens come from, and provide early warning before invasion, thus early intervention direct to the infection source can be done.
Method: We broaden our thinking, pour reasonable resources, at a reasonable speed, to develop sequencing based pathogens" automatic monitoring devices, reasonable allocate, combine with Internet of things(Internet of people), big data and other technologies, gradually build the library and network, form the new generation of microbial defense system, crack pathogens" stealth skill, precisely monitoring the environmental pathogens before they do evil.
At present, we keep security and early warning through video monitoring system. The principle work in the field of microbes" monitoring and early warning too.
I will discuss following points: Broad spectrum, Resolution, Automation, Minimal maintenance, Network, Intelligent, Traceability, Dual track, Topological allocation, Portability or become automobile accessory of one man vehicle.
Broad spectrum: The conventional method is specific test, which struggled when variation happened. To solve the problem we could seek broad spectrum, morphological observation is significantly less suitable than sequencing to tell species, and Moore"s Law will gradually make sequencing economically accessible. Oxford Nanopore"s MinION is probably the ancestor of future monitoring sequencers. The two major challenges: How to extract nucleic acid without reagent kits, and anchor guiding complex to the sequencing membrane.
Resolution: Depend on purity and coverage the physical extract technique could achieve, and the parameter configuration of the monitoring sequencer, such as the read length, the ratio of the total copies to nanopores in use, the interval time to sample, and the resampling rate in sample, etc. Some techniques that rely on local computing power, such as the ReadUntil technique, can help improve efficiency.
Automation: To sampling different samples(gas, liquid, solid surface) automatically, dust catcher and its different suction heads is a good reference.
Minimal maintenance: Kit extraction turn to physical or other freeloader mode. I think the most consumable component may be the nanopore plus nucleic acid guiding complex membrane.
Networking, Intelligent and Traceability: Require interdisciplinary cooperation, to enable automatic processing of unusual signals, multi-device calibration and cloud alarm. Refer mobile phone"s step counting and movement track recording.
Dual track: The first generation may perform poor and limits its usage to only monitor, but later generations may fit both monitoring and diagnostic usages.
Topological allocation: Under the guidance of mathematical modeling, crowd place, human-animal boundary area.
Become automobile accessory of one man vehicle: Require interdisciplinary cooperation. When one man vehicle system(personal traffic, reside, data terminal and cloud system) is successfully embrace and replace the nowadays cellphone system, the most economical allocation is one per capita with user. By fine tuning, sequencer can also be used to identify infectious pathogens from user, user"s whole genome sequencing and monitor newly emerging mutations. If one man vehicle system is implemented earlier than microbe monitoring device, it may also provide irreplaceable reagents from vehicle source in early days. Besides as an aircraft carrier, it can also share computing power, GPS, wireless communication networking, tire source centrifuge, gas sampling bin, etc. Furthermore, vehicle is more comfortable than mask or gas mask thus suitable for long-time usage,while other sensors on-board can improve the efficiency of epidemiological investigation.
