3D Reactor Paper Spray Mass Spectrometry For Detection Of Disease Markers In Blood

The detection of disease markers is essential for the prevention,diagnosis,treatment and prognosis of diseases.It can assess the risk of disease occurrence,reduce the cost of disease treatment,and even avoid the occurrence of disease.The body fluid(mainly blood)based detection by mass spectrometry is a convenient,noninvasive(or minimally invasive)and patient-friendly detection method,which has found broad applications in the clinic.However,in the sample analysis by conventional mass spectrometry,pretreatment is usually needed which is typically complicated,time-consuming,high-cost and requires well-treated operators.Thus,it is an urgent need for the development of a simple,sensitive,effective and low-cost quantitative method for the analysis of disease markers in order to meet clinical requirements.In this work,we have designed a 3D reactor paper spray(3D-RPS)mass spectrometry platform,which integrates chemical reaction and detection,for the analysis of blood disease markers.Through 3D printing technology,this platform has been fabricated which integrates enzyme-catalyzed reaction(or chain replacement reaction),analyte transfer,paper spray detection and temperature control.In the detection of butyryl cholinesterase(BuChE,a marker of liver disease and organophosphorus poisoning),the current 3D-RPS method demonstrated the same accuracy as the commercial Ellman method.Furthermore,in the detection of miRNA-141(abnormal expression in prostate cancer patients),we combined 3D-RPS method with toehold-mediated strand displacement reaction(TSDR),and reached the accurate detection of miRNA-141 by the nanoparticle-assisted signal amplification.For the first time,the paper spray mass spectrometry was used in the high sensitive and quantitative detection of miRNA and expanded the application scope of paper spray mass spectrometryCompared with the clinical used methods,the 3D-RPS method proposed in this paper demonstrated similar,or even higher accuracy.This method also effectively reduces the detection cost and operation difficulty,showing high practical application prospects.In addition,this method could also guide the detection of other kinds of body fluid-based disease markers.