Mass spectrometry, which measures the mass-to-charge ratio of ions, is particularly suited for the characterization of biomolecules, especially in biomanufacturing operations. This technology yields a wealth of information on its targets, the elemental or isotopic signature of a sample, the masses of the molecules comprising the sample, and their chemical identities.
“We use mass spectrometry to determine the properties of relatively simple samples such as a chemical standard’s purity, as well as characterizing complex mixtures such as proteomes and metabolomes,” says Daniel Lopez-Ferrer, PhD, senior manager, vertical marketing proteomics at Thermo Fisher Scientific.
But there are limitations to these technologies, principally the loss of information and the lack of statistical power. While it is feasible to identify and quantify thousands of proteins in a reproducible manner, the number of replicate measurements for a given protein is limited, usually to 1 to 3, due to the cost and complexity of the experimental setups.
Factoring in the loss of information due to “missed values” may reduce the statistical power further, producing data bias. For this reason, the field is currently transitioning towards standardization to enable higher throughput and advanced automation. These improvements are geared to increase the overall productivity, making the analysis of larger numbers of samples more amenable.
Yet, these limitations do not reduce the power and versatility of mass spec for analyzing such questions as ligand binding. This problem is difficult to attack with conventional methodology—to address exactly how the ligand fits into the binding site of a protein is virtually impossible to consider without the use of mass spec.
In advancing Thermo’s instrumentation, one key consideration is ease of use. Historically, reduction in size meant decreased performance and sensitivity, but the company’s life sciences MS group is working to break this adverse relationship.
“We pursue size reduction and user experience as a pivotal consideration,” Lopez-Ferrer continued. “It’s an important step toward democratization and reduction of a steep learning curve.”
Sample preparation is another important element of mass spec. At present there are numerous steps involved, and it is a long and complex process, which demands highly trained personnel, frequently at the PhD level. So, these considerations formed a critical component of the company’s new product line.
“We are working to reduce the number of steps and introduce automation to reduce the cost of the process,” said Lopez-Ferrer opined. “We have brilliant minds in our proteomics labs spending a lot of time doing sample prep, and we want to free them up to pursue projects where they can bring more value.”
Therefore, an important strategy for lowering costs and saving skilled labor time is the introduction of kits to automate various steps in the analytical process.
One of Thermo Fisher’s most important analytical tools is the Orbitrap mass analyzer, in which ions are electrostatically trapped around a central spindle caused by their electrostatic attraction to the inner electrode, which is balanced by their inertia.
“We launched the Orbitrap Eclipse Tribrid mass spectrometer last year, which radically increased our ability to evaluate intact proteins in their native state,” Lopez-Ferrer explained. “In recent years there have been dramatic improvements in MS technology, which further enhanced the performance and productivity for structural proteomics.”