Bioanalysis Zone

An author’s perspective: Gary Van Berkel on immediate drop on demand technology coupled with mass spectrometry


To help provide insight into the recent article published in Bioanalysis: Immediate drop on demand technology (I-DOT) coupled with mass spectrometry via an open port sampling interface, we spoke with author Gary Van Berkel, Distinguished Scientist and Group Leader at the Mass Spectrometry and Laser Spectroscopy Group at Oak Ridge National Laboratory (TN, USA). Gary explains why he felt this was an important area for bioanalysis and worthy of publication. His work focuses on emerging technologies and immediate drop on demand technology coupled with mass spectrometry.

“I am a Research Scientist and Group Leader in the Mass Spectrometry and Laser Spectroscopy Group at Oak Ridge National Laboratory (TN, USA). I earned my BA in Chemistry from Lawrence University (WI, USA) and my PhD in Analytical Chemistry from Washington State University (WA, USA). My graduate school work focused on trace metal quantitation (using neutron activation analysis) and metal speciation in fossil fuels and source rocks (using mass spectrometry) in relation to the fundamentals of petroleum formation and source rock‐oil field correlations for enhanced oil prospecting. From this work sprang an interest in developing mass spectrometry based detection and characterization methods for geoporphyrins and ultimately a focus on ionization sources for mass spectrometry. That interest brought me to Oak Ridge National Laboratory as a postdoctoral associate where I was fortunate to work with and learn from two of the best young mass spectrometrists in the business at that time, Drs Gary Glish (University of North Carolina at Chapel Hill, NC, USA) and Scott McLuckey (Purdue University, IN, USA). My most notable work in the 1990’s led to an elucidation of the electrochemical aspects of electrospray ionization. Today my work is focused on atmospheric pressure ion sources and on the novel configurations and applications of these ion sources to solve analytical problems. Most recently we have been investigating and developing atmospheric pressure sampling/ionization probes and the instrumental techniques and methods for high-throughput analysis and chemical imaging with mass spectrometry. We are fortunate to have been awarded many accolades for the patents, research and publications, as well as the technology transfer and commercialization aspects of these efforts.”

1. Could you describe the key factors that need to be considered when introducing a new, emerging technology?

‘Use inspired basic research’ and ‘value innovation’ are two parallel concepts, one from the science world and the other from the business world, which I encourage in our group as we work to advance analytical chemistry measurement science. The first concept comes from Stokes’ book, Pasteur’s Quadrant (1997), in which he discusses the important dynamic between basic and applied research. Stokes makes the case that use-inspired basic research, fundamental work aimed at addressing problems that when overcome clearly benefit the human condition, should be one important focus of government funded science. Analytical chemistry by its very definition is use-inspired basic research, as innovation is done with an eye towards overcoming important measurement science deficiencies. The second concept, value innovation, comes from the book Blue Ocean Strategy by Kim and Mauborgne (2005). This business book deals with creating or inventing into uncontested market space (i.e., a blue ocean) by focusing equally on value and innovation. Bleeding (or cutting)-edge technology isn’t as impactful on the market or customer unless there is appropriate utility, price and cost positions. We have found value innovation success with some of our emerging analytical technologies by having industrial partners closely aligned within our basic research program helping to steer the work towards a blue ocean.

You can find more content on emerging technologies: DMPK and bioanalysis of small molecules on our Spotlight page.

2. What are the advantages/disadvantages of using immediate drop on demand technology coupled with mass spectrometry?

The rational for coupling of the immediate drop on demand technology (I-DOT) with mass spectrometry comes from a general desire to simplify and speed up the analysis of liquid analyte samples that have been previously prepared for analysis by atmospheric pressure (AP) ionization mass spectrometry. One approach to this end goal is the analysis of individual or multiple droplets from the sample solution via various non-contact dispensing techniques. Analysis of individual sample droplets is a means to limit sample consumption and potentially transfer all the sample material into an ionization source more efficiently. The I-DOT provides fully automated non-contact dispensing of liquid samples from a special 96-well microtiter plate vertically down towards specified locations on a target plate, typically for the formation of planar arrays for a variety of chemical or biological investigations. Here we couple this system to a mass spectrometer via the open port sampling interface (OPSI) developed in our group at Oak Ridge National Laboratory. The OPSI is a vertically aligned, continuous-flow, coaxial-tube sampling probe. Individual drops from the wells of the I-DOT are captured in the OPSI and carried to the mass spectrometer for ionization and mass analysis. With this simple coupling maximum sample analysis throughput was determined to be as fast as 5 seconds per sample translating to an 8 minute analysis time for a 96 well microtiter plate. Low nanoliter volumes of nanomolar analyte solutions provided adequate signal levels for either quantitative or qualitative analysis. We also showed that this combination was not limited to the analysis of relatively small mass analytes, but could be used for the analysis of macromolecules like the protein cytochrome-c.

3. What further advances do you envisage with immediate drop on demand technology coupled with mass spectrometry in the future?

In the short term there are some relatively simple improvements in both the I-DOT instrumentation (e.g., software, ability handle 384 well plates or larger) and the OPSI (reducing sample transport time) that would improve general use and sample throughput of the I-DOT-OPSI-MS combination. A longer term vision is for the present work to open up research by others with the OPSI and the OSPI with the I-DOT (and other drop dispense technologies) particularly those amenable to directly dispensing from high well density microtiter plates. In general, the non-contact, no moving parts, self-cleaning, low pressure continuous flow aspects of the OPSI should facilitate simple and effective analysis of multiple sample types (for example – liquid drops, ablated particles, aerosols) – with on-line mass spectrometry.

Reference: Van Berkel GJ, Kertesz V and Boeltz H. Immediate drop on demand technology (I-DOT) coupled with mass spectrometry via an open port sampling interface. Bioanalysis 9(21): 1667–1679 (2017)

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