Development of Novel Noble Metal Mass Spectrometry Chips for in Vitro Diagnostics

Author:Sun Xu Ming

Supervisor:qian kun


Degree Year:2018





In vitro diagnostics(IVD)refers to in vitro test of biological specimens and contributes to two-thirds of clinical diagnosis.Compared with the traumatic surgical exploration and radiological imaging,in vitro diagnosis has the advantages of convenience,low trauma,ease of operation and economy.Metabolic analysis is more distal over proteomic and genomic approaches toward precision diagnostics with some advantages: metabolites are the result of changes in physiological and pathological conditions which can accurately reflect the status of organisms,and the biochemical metabolic pathways of many endogenous metabolite molecules have been confirmed with relatively few types and quantities.Metabolic analysis relies on rationally designed materials and device for sample treatment and metabolite detection dealing with diverse biological specimens for practical diagnostic applications.In this paper,a new type of mass spectrometry chip was prepared and applicated for in vitro diagnosis based on metabolic fingerprinting.A series of chips were firstly constructed through controlled particle synthesis,dip-coating,and gold sputtering: the chip could be integrated with microarrays for laboratory automation and micro-/nanoscaled experiments using tiny amounts of biosamples(500 nL);and the optimization chip fabrication parameters were obtained by controlling the gold sputtering time,silica size and concentration for laser desorption/ionization mass spectrometry detection of serum and exosomes.Secondly,on-chip in vitro metabolic diagnosis of early stage lung cancer patients using serum and exosomes were demonstrated with results of 0.726 and 0.716 and some selected key m/z values were anticipated to serve as potential metabolic markers.Thirdly,silver mass spectrometry chips were fabricated and electric field of core-shell particles were simulated based on finite-difference time-domain method for optimization of chip fabrication parameters,and we detected as few as 10 to 100 intact bacterial cells based on the silver chip.Fourthly,platinum mass spectrometry chips were developed for in vitro metabolic diagnosis of stroke subtype of atherothrombosis and small artery occlusion and a clear group separation was observed between atherothrombosis and healthy control.In a word,our work makes solid contributions to the design of materials and device for advanced metabolic analysis toward clinical diagnosis and sensitive and fast identification of bacteria.