A Simple 3D-Printed Enzyme Reactor Paper Spray Mass Spectrometry Platform for Detecting BuChE Activity in Human Serum

Abstract

To achieve personalized healthcare, a quick, accurate, and high-throughput method to detect disease biomarkers is essential. In the traditional practice, mass spectrometry is one of the most powerful tools and is widely studied. However, the test of human serum usually requires complicated sample pretreatment, tedious operations, and precise condition control, especially for the detection of enzymes as biomarkers. As butyrylcholinesterase (BuChE) has an indicative significance in detecting degenerative disease, liver injury, and organophosphate poisoning, the quick quantification of BuChE is of vital importance to the clinic. In this paper, we report the design and fabrication of a portable 3D-printed enzyme reactor paper spray cartridge (3D ER-PS) with integrated functions: temperature control, enzyme reaction, analyte transfer, and paper spray ionization. Coupled with mass spectrometry, quantitative testing of BuChE activity in human serum was realized conveniently and accurately. While it only requires very simple sample preparation, the results from current 3D ER-PS approach are well consistent with those obtained using Ellman’s method. This 3D ER-PS platform not only provides a novel solution for the liquid biopsy of BuChE in clinics but also contributes to the development of quick and targeted medical approaches for analyzing other types of serum biomarker molecules in the field of disease diagnosis.

Build, Share and Remix: 3D Printing for Speeding Up the Innovation Cycles in Ambient Ionisation Mass Spectrometry (AIMS)

“…The PLA devices could analyse up to six samples. Multiple functions were integrated into this gadget: temperature control, enzyme reaction, analyte transfer, and PSI [39].…”

Leveraging 3D printing to enhance mass spectrometry: A review

“…In a second system, a 3D-printed sample treatment module was used to perform an enzymatic reaction on a paper based substrate (Fig. 4D), that could afterwards be easily moved onto the paper spray tips, which were then used for the analysis after passive sample transfer [93]. A third approach describes a 3D-printed device that could be connected to a commercial (non-3D-printed) cartridge for the direct capture of chemical warfare agents in aerosol onto the paper substrate in the cartridge (Fig.…”

“…Copyright 2017 American Chemical Society. (D) Cartridge that combines an enzyme reactor to PS-MS; adapted with permission from Yang et al [93]. Copyright 2019 American Chemical Society.…”

Peptide and protein assays using customizable bio-affinity arrays combined with ambient ionization mass spectrometry

“…This integrated AIMS platform allows the selective capturing of phosphopeptides and cis-diol biomolecules or target proteins from complex matrices on the arbitrarily predesigned BAAs via affinity interactions ranging from coordination chemistry, covalent bonding to biological recognition, followed by successively extraction, ionization, and MS readout of the captured target species within seconds after minimum sample pretreatment. Unlike the conventional SPME-MS, in which one SPME tip (fiber, 44 paper, 45,46 Al foil 47 or coated blade 34,35 ) only affords the extraction and spray of a single sample, the BAAs integrated in one slide augment the throughput of biological sample handling by continuous manipulation of tens of samples. In this sense, with the arsenal of affinity probes in hand, the BAAs can be easily customized to implement the MS analysis of desired target proteins/peptides.…”