The analysis of cells is fundamental to understanding functioning biological systems, impacting the discovery of oncology drugs, DMPK and toxicology studies for all pharmaceuticals. Analysis of cell lysates can provide data sets that allow scientists to better understand, predict and influence the factors that underlie cell health, production, function and death.
A recently published paper from our science founder, J. Michael Ramsey, and his team at the University of North Carolina at Chapel Hill, looks at hemoglobin as an example. Ion exchange high performance liquid chromatography (HPLC) is commonly used for measuring glycated hemoglobin (HbA1c), a modification of hemoglobin. The measurement of HbA1c is an important diagnostic tool to detect and manage diabetes in patients. With 1.4 million Americans receiving a diabetes diagnoses every year, the correct analysis and assessment of these cells is imperative.
All cells contain thousands of compounds in constant metabolomic flux, so capturing an accurate ‘snap-shot’ requires fast analysis and minimal sample preparation. Due to the complex makeup of cells, analyzing them can be a lengthy and complicated process. For example, a common LC-mass spec variant that scientists leverage for analysis in the lab uses hydrophilic interaction chromatography (HILIC) separations to capture polar metabolites. HILIC separations typically involve long run times and require significant sample preparation – both of which result in significant overhead and risk that the metabolic profile will be changed by the preparation itself. For scientists with a large volume of sample backlog, lengthy sample preparation and 30-minute analysis wait times are not ideal.
Earlier this year, we launched ZipChipTM, an innovative, front-end system that provides seamless, high-quality separation capabilities for traditional mass spectrometers (MS). The result is fast analysis for a broad range of biomolecules, including cell lysates. ZipChip provides fast, quantitative separations and full MS data with minimal sample preparation.
Here is how it works: using ZipChip HS, one of two ZipChips available to customers, a variety of metabolites can be analyzed – including cell lysates from whole blood, cultured samples, growth media and a variety of other matrices. Once the sample is loaded, ZipChip HS uses integrated microfluidic technology to prepare, separate by capillary electrophoresis (CE), and then electrospray (ESI) biological samples directly into traditional MS instruments.
The prep and background electrolytes are gentle on the lysates and gentle on the MS, providing customers with confidence that their analysis is reliable and matches the metabolomic state of the cells when collected. The upfront sample prep time for small molecules and metabolites is also reduced as the system includes a simple protein crash and quick spin filter before direct injection into the device. The ZipChip system also provides a full MS data analysis in under three minutes and, unlike LC techniques, there is no trade-off between speed and the amount of sample needed.
By incorporating ZipChip into the cell analysis process, we are dramatically improving what users can see with their MS instruments; transforming time-consuming sample runs into fast, everyday analysis. For more information about how this technology has been applied to cell analysis, we invite you to read this recently published technical paper in Analytical Chemistry, that looks at hemoglobin as an example, titled “Analysis of Hemoglobin Glycation Using Microfluidic CE-MS: A Rapid, Mass Spectrometry Compatible Method for Assessing Diabetes Management.” This piece demonstrates that these analyses produce results that are comparable or better than established techniques in less time.