Rapid Detection Of Chemical And Biological Warfare Agents By Ambient Ionization Mass Spectrometry

It is very important for the rapid alarm and timely protection to detect chemical and biological warfare agents(CBWAs)quickly and accurately.Unlike a laboratory mass spectrometry,mobile mass spectrometry including vehicle-mounted or portable mass spectrometry has the advantage of on-site,online and fast detection.However,mobile mass spectrometry mostly used electron ionization(EI)source,and it could detect volatile chemical warfare agents.When using EI to ionize chemical warfare agents in soil or water and solid powder agents,derivatization,headspace sampling,solid-phase or liquid-phase extraction were needed.Biological samples such as peptides or proteins could not be ionized by EI.Therefore,it was difficult to meet the military needs of broad-spectrum and rapid detection of CBWAs.Ambient ionization can directly ionize the sample under atmospheric pressure,without or with simple sample pretreatment,which has the characteristics of simple construction,rapid desorption and ionization,and multi-ion source integration.Because the ionization source was placed in the atmosphere,it coud decrease the volume and weight of vacuum system and it was easy to realize mass spectrometry miniaturization and field application.Ambient ionization technology was the research hotspot of the field mass spectrometry domain.This paper followed the requirement of rapid detection of C BWAs,and the problems,such as lacking rapid detection methods of CBWAs of different types and phases based on ambient ionization,and the CBWAs ambient ionization mechanism was not enturely clear,and parameter optimization lacking quantitative analysis and poor reproducibility of quantitative detection of ambient ionization were studied.Ambient ionization experimental devices of CBWAs were constructed.It studied the ambient ionization mechanisms of CBWAs.Rapid detection methods of C BWAs with different phases and types based on ambient ionization-mass spectrometry were established.It fulfilled the rapid detection with some characteristics,such as vacuum ionization to atmospheric ionization,and gas phase chemical warfare agents to solid or liquid C BWAs,and covering chemical warfare agents of small molecular weight and biological toxin of large molecular weight.It provided a new way to the rapid detection of CBWAs based on mass spectrometry.The main contents were as follows.1.Ambient ionization experimental devices including thermal desorption-low temperature plasma(TD-LTP)ionization,micro-extraction by packed sorbent-nano electrospray ionization(MEPS-Nano ESI)and laser desorption ionization(LDI)were constructed.The significant degree of the relevant parameters affecting the ambient ionization efficiency was analyzed quantitatively by multivariate repeated experiment analysis of variance(MR-ANOVA)method.The parameters of the LTP ionization device were optomized,such as the velocity of discharge gas,and the distance between ionization source outlet and samp le.The parameters of the Nano ESI device were optimized,such as the distance between the metal needle tip and the mass spectrometry inlet,and the electrospray voltage.The parameters of the LDI device were optimized,such as the horizontal distance between the laser irradiation position and the mass spectrometry inlet,and the laser repetition rate.2.The ambient ioniztion mechanisms of chemical warfare agents and their simulants and biological toxin were studied.(1)It proved that the LTP ionization process of Sarin(GB)and VX is proton transfer with water cluster ions.H~+comes from water molecules and solvent molecules in the air,and H~+mostly combined with phosphorus oxygen double bond(P=O).Proton and charge migration existed in the collision-induced dissociation of pseudo molecular ions of GB,VX and their simulants.The LTP ionization process of sulfur mustard(HD)and its simulant were mainly penning direct ionization.(2)It proved that H~+was derived from the external environment during the nano ESI of chemical warfare agent simulants,such as DMMP and tributyl phosphate.There was hydrogen proton exchange between gas phase ions and the outside atmosphere.(3)It proved that H~+was derived from the solvent in the nano ESI and LDI process of aconitine and conotoxin.There was hydrogen proton exchange between the gas phase ions and the outside atmosphere in the LDI process of conotoxin.3.The rapid detecion methods of chemical warfare agent simulants in soil and hydrolysis products in water and volatile and solid powder chemical warfare agents by ambient ionization-mass spectrometry were studied.(1)A new detection method of GB and HD hydrolysis products in the water based on microextraction by packed sorbent combined with nano ESI mass spectrometry was proposed.The detection limit of isopropyl methylphosphonic acid(IMP A),methylphosphonic acid(MPA)was 1ng/m L.The proposed method was found to be linear between 1ng/m L and 100ng/m L(R~2>0.991)with precision of≤12.4%and recovery rates were 87.8%and 101.5%(5ng/m L).The detection limit of thiodiglycol(TDG)was 1ng/m L.The proposed method was found to be linear between 5ng/m L and 100ng/m L(R~2>0.991)with precision of≤10.7%and recovery rate was 107.8%(40ng/m L).The detection time of the proposed method was less than 10 minutes(including extraction and elution time)without derivatization,and it fulfilled the rapid detection of chemical warfare agent hydrolysis products in the water.(2)A new detection method of nerve agent and blister agent simulants in the soil based on thermal desorption-LTP ionization-mass spectrometry(TD-LTP-MS)was proposed.The detection limit of DMMP and TBP was pg level.The proposed method was found to be linear between 5pg and 500ng(R~2>0.990)with precision of≤19.5%,and response time of DMMP was 5.8s.The detection limit of2-chloroethyl ethylsulfide(CEES)was ng level.The proposed method was found to be linear between 5ng and 500ng(R~2=0.9997)with precision of≤8.6%,and the response time of C EES was 5.4s.It fulfilled the direct detection of chemical warfare agent simulants in the soil.(3)A detection method of GB based on TD-LTP-MS was established,and the detection limit was 1μg/m L.The proposed method was found to be linear between 1μg/m L and 50μg/m L(R~2=0.9923)with precision of≤6.0%,and the response time was 9.7s.It fulfilled the rapid detection of volatile chemical warfare agent.(4)A detection method of 3-quinuclidinyl benzilate(BZ)based on nano ESI-MS was established,and the detection limit was 100ng/m L.The proposed method was found to be linear between 1μg/m L and 20μg/m L(R~2=0.9901)with precision of≤17.1%,and the response time was 3.1s.It fulfilled the rapid detection of solid powder chemical warfare agent.4.The rapid detecion methods of biological toxin by LDI/ESI-MS were studied,and it fulfilled the rapid detection of biological toxin with molecular weight ranging from several hundred to tens of thousands.(1)A detection method of aconitine and conotoxin based on LDI-MS was established,and the detection limit was 1ng/m L.The proposed method was found to be linear between 1ng/m L and 20ng/m L(R~2=0.9689and R~2=0.9836)with precision of≤28.2%,and the response time was 2.6s.(2)A detection method of tetrodotoxin and conotoxin based on nano ESI-MS was established.The detection limit of tetrodotoxin was 1ng/m L,and the proposed method was found to be linear between 1ng/m L and 20ng/m L(R~2=0.9919)with precision of≤14.1%,and the response time was 3.8s.The detection limit of conotoxin was 2ng/m L,and the proposed method was found to be linear between 2ng/m L and 20ng/m L(R~2=0.9986)with precision of≤7.2%,and the response time was 5.4s.(3)A detection method of myoglobin based on ESI-MS was established,and the detection limit of myoglobin was1μg/m L,and the proposed method was found to be linear between 5μg/m L and100μg/m L(R~2=0.9908)with precision of≤21.4%,and the response time was 2.7s.In conclusion,the new rapid detection methods of CBWAs by ambient ionization mass spectrometry were proposed.The methods were used to detect the CWA simulants under the disturbance of vegetation smoke and bio logical toxin on the surface of equipment.The research results could provide a new technical way for the field rapid reconnaissance of CBWAs.In the future,the ambient ionization coupled with miniature mass spectrometry could be applied to the rapid detection of CBWAs in the field.