Power (Wish) List

Alexander Makarov: A technique to “see” a single molecule with atomic resolution directly and rapidly.

Teresa Rocha Santos: Screening devices for fast laboratory and on-site determinations of emerging contaminants are lacking. Specifically for microplastics, there is a need for instrumentation for the quick and easy identification and quantification of polymeric particles. As the particle size decreases the difficulty rises exponentially.

Wim De Malsche: Chromatographic systems should be standard equipped with two types of detectors, one for quantification and one for identification. The needed technology is out there: current detection technologies allow for localized detection, current (miniaturized) flow technologies allow for detection without messing up the separation during detection.

Frances S. Ligler: Inexpensive methods for nondestructive analysis of living systems in 4 dimensions at the cell and molecular level, including deep in tissues. Many investigators are currently tackling this problem, employing technologies such as IR, 2-photon, multispectral, impedance or quantum spectroscopy, usually with fairly expensive equipment. Useful solutions will be inexpensive, flexible and may not even require direct contact with the tissue. Lots of challenges remain to solve this problem.

Koen Sandra: The toolbox will never be complete. The life sciences domain is so dynamic and the diverse analytical requests come at such a high pace that we continuously need to challenge and reinvent the analytical arsenal. This creates interesting opportunities and keeps us going. Today, for example, there is a need for technologies that shed light on the structural details of large molecular assemblies, such as transgene-carrying viral vectors and mRNA-encapsulating lipid nanoparticles. This particulate matter again drastically raises the bar when it comes to structural characterization. But rest assured, our analytical community will also crack that code as well as the many others that will follow.

What about mass spec?
 

Torsten Schmidt: I have been using compound-specific stable isotope analysis (CSIA) in my group to study contaminant sources and transformations since my postdoc days. When I started, I expected the field to expand exponentially because of the unique information provided by isotopic composition and its changes that no other analytical method can offer. Although the use of CSIA has highly successful niches and the instruments have been commercially available for decades, widespread application is still hampered by the rather sophisticated methods that require special expertise and the absence of further ground-breaking instrumental developments. With the combined efforts of manufacturers and researchers, this may be about to change if widely available high-resolution mass spectrometers achieve sufficient precision to measure the small differences in natural abundance isotopic composition. The possibilities of performing multi-isotope analysis of compounds and position-specific isotope analysis with specific mass fragments are almost limitless. In recent years, there have been some exciting reports demonstrating the potential of HRMS-based SIA, but the community is small and progress has been slow.

Robert Kennedy: I'd love to see an ionization method that is as general as ESI but not limited by ionization suppression effects… That would be quite useful. I also think we need better compound identification tools for small molecules. NMR is the gold standard but requires too much material and time for many projects. MS is not there yet in terms of quickly providing unequivocal identifications for many compounds.

Lingjun Li: Hardware wise, it would be wonderful to have better instrumentation that offers highly sensitive ionization source that works for a broad range of biomolecules with less ionization suppression and deeper molecular coverage; software wise, we would benefit from having improved computational tools that can integrate multidimensional data acquired from disparate techniques and complementary modalities to achieve a more comprehensive understanding of biological systems and their functioning in health and disease.

Stefan van Leeuwen: One important aspect is how to get to a high level of confidence for identification and quantification in mass spectrometry when authentic reference standards are lacking. Historically, we used authentic reference standards for unequivocal compound identification, and reliable quantification. As regards HRMS (e.g. non target screening), there is a high degree of confidence that this technique may bring, but currently the highest degree of confidence cannot be achieved without confirmation through an authentic reference standard. The question that rises here: can we increase the availability of reference standards, or can analytical scientists come up with smart solutions to create a high level of confidence where society can rely on, without reference standards.

Davy Guillarme: A mass spectrometry-based detector capable of providing high sensitivity for analyzing very large molecules, such as mAbs, mRNA, and AAVs, would be highly valuable. While ESI-MS performs reasonably well for such large molecules, its sensitivity is often insufficient. The development of a new or revolutionary ionization mode and/or mass analyzer specifically designed for very large molecules would be greatly welcomed.

Michael Gonsior: Extremely high resolution MS with extreme sensitivity and fast response times.

R. Graham Cooks: The same item that has been missing for two decades, a powerful portable commercial mass spectrometer for point-of-care measurements. It must privilege speed over other parameters and must have MS/MS for chemical specificity.

Gary Siuzdak: In metabolomics, and chemical analysis in general, effectively filtering out artifactual (in-source fragmentation) mass spectrometry data from datasets.