Development of VSSI-probe technology for in situ probing biological systems using mass spectrometry - Project Summary
Mass spectrometry (MS) is a powerful tool for biological studies, which has found a wide range of applications
including proteomics, metabolomics, glycomics, lipidomics, and structural biology. While most of the existing MS
applications are extraction-based batch analysis, using MS for in situ or in vivo analysis of biological samples
has become increasingly important to enable new biological discoveries. The past decade has witnessed the
rapid development of interfacing methods for direct MS analysis of various biological samples from tissue slices
to single cells. However, existing methods still have difficulties in studying living and dynamic biological systems
in a non-invasive manner and in situ MS experiments are primarily performed by MS research groups due to the
involvement of complex instrument setups. As a result, these limitations significantly hinder the progress of using
direct MS for biological discoveries. To address the unmet need for in situ MS analysis of biological systems,
our objective is to develop a direct MS method, vibrating sharp-edge spray ionization probe (VSSI-probe), that
is simple, easy to use, biocompatible, and amenable to high speed sampling. Compared to existing methods,
the proposed VSSI-probe is amenable to fast sampling, highly biocompatible, voltage-free, easy to operate, and
substantially less expensive. Therefore, we expect that once demonstrated, the proposed VSSI-probe will enable
new MS applications as well as improve the adoption of direct MS analysis in the biological community. In
particular, we will (1) optimize the performance of the VSSI-probe for high sensitivity MS detection;(2)
demonstrate a high-throughput VSSI-probe platform for studying fast biological reactions;(3) demonstrate the
utility of VSSI-probe in studying a delicate and dynamic biological system of lipid/protein aggregates interaction.
(4) demonstrate the high spatial resolution sampling capability of VSSI-probe for studying metabolites directly
from bacterial colony. With the unprecedented capability and flexibility of probing biological samples, the
proposed VSSI-probe will enable a broad range of biological applications that requires fast and biocompatible
sampling including enzymology, cell monitoring, lipid bilayer chemistry, and real time intraoperative diagnosis.
The simplicity, low cost, and compatibility with existing mass analyzers of the proposed system will also greatly
reduce the technical barrier for adopting this technology by non-MS groups thereby expanding applications of
direct MS to more diverse biological problems.
