Since the development of nanostructure-initiator mass spectrometry (NIMS), we have been working to find a way of producing these surfaces without the use of electrochemical HF etching, which poses both major safety implications and greatly limits the wide-spread implementation of NIMS. Here, we show that inductively coupled plasma (ICP) reactive ion etching (RIE), a common, safe and highly controllable ‘dry’ etching process can be used to produce NIMS surfaces. In this work, we studied different plasma etching conditions, and explored the relationship between surface nanostructures and its performance as NIMS substrates. Although these NIMS have lower sensitivity (attomole level for verapamil) than HF electrochemically etched surfaces, we find it is suitable for analysis of a diversity of metabolites making it suitable for many if not most applications and can be further improved owing to the large parameter space of ICP etching process. We also observe a very interesting and yet unexplained metabolite selectivity associated with different etching parameters which may prove useful for reducing signal from interferences. We believe that by developing this much more accessible method for creating nanostructured surfaces, the NIMS technique will become widely used in more academic groups and industries, especially, since this approach lends itself to clean-room microfabrication for integration of NIMS into microdevices.
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