Dr. J. Michael Ramsey, the scientific founder of our company and the Goldby Distinguished Professor of Chemistry at the University of North Carolina (UNC), Chapel Hill, recently spoke at the Greater Boston Mass Spectrometry Discussion Group’s (GMBSDG) October meeting. Being part of the local MS community, our team at 908 Devices really values the GBMSDG meetings, which provide a forum to exchange ideas informally in a social setting as well as hosting consistently impressive technical talks. We were excited when Mike was selected to deliver the keynote at the October meeting, sponsored by Pfizer.
Mike has a long-standing history with the technologies that power our three current commercial devices. He began to explore microfluidic structures for capillary electrophoresis in the ‘90s. This launched the miniaturization theme of his research group at UNC. His team focuses extensively on utilizing micro- and nanofabrication strategies to create devices that gather chemical and biochemical information.
Prior to the founding of 908 Devices, Mike was the Science Founder of Caliper Technologies (later renamed Caliper Life Sciences and acquired by PerkinElmer in 2011) based on his foundational work in microfluidics. A common interest and Mike’s groundbreaking work on the miniaturization of mass spectrometry connected him with Dr. Kevin Knopp, and soon after 908 Devices was born.
In his GBMSDG presentation, Mike spoke about how microfabricated technologies can be used to address bioanalytical measurement problems. The talk predominantly focused on microfluidic capillary electrophoresis electrospray ionization (CE-ESI) and he shared perspective on the technology’s historical development.
Despite the location being an hour’s drive from downtown Boston and Cambridge, the event was well attended by more than 75 professionals from academia, pharmaceutical, biotechnology and environmental research.
Developing of Microfluidic CE-ESI
Mike and his team have been developing fast microfluidic CE separations for more than a decade. The presentation covered three separate and significant scientific breakthroughs necessary for an integrated microfluidic system that produces fast, high-resolution separations and a sensitive, stable electrospray for MS detection.
The first of these breakthroughs was the development of the novel surface chemistries that are applied to the microfluidic channels on chip. These coatings better control ion flow through the channels, are key to long-term robustness and enable a single chip to work for a wide range of analytes. To demonstrate this, Mike’s presentation featured data from intact proteins down to the smallest metabolites. Optimal coatings are a key part of recognizing the theoretical performance advantages of microfluidic technology in real analytical methods. As an example, the separations shown in 2-3 minutes with microfluidic CE-ESI would typically take 20 minutes or longer, if they could be completed at all, when traditional fused silica capillaries or LC methods are used.
The second advance is the novel approach of electrospraying directly from the corner of the chip. This allows for ions to be created from a single integrated system, removing the need for a separate electrospray interface and the associated junctions and connections with a distinct separation device. Since dead-volume and junctions slow separations and broaden peaks, this advance not only dramatically simplifies the whole system but, as stated, is key to dramatic performance improvements.
The third breakthrough is the implementation of transient isotachophoresis (tITP) on the same integrated chip. Here, tITP uses a leading electrolyte to pre-concentrate analytes, providing a significant improvement (typically ~10x) in the LOD. In biological or biopharma analyses, where high salt levels are common, the appropriate implementations of tITP also remove the need for sample preparation or clean-up techniques that other methods require. The removal of salts occurs on chip as part of the analyte pre-concentration.
Tackling Challenging Applications with Microfluidic CE-ESI
The advances that have stemmed from microfluidic CE-ESI have allowed users to take on new challenges. Microfluidic CE-ESI can separate the following sample types easily and in record time, allowing faster and more accurate MS analysis:
- Small molecules from cell extracts
- Amino acids from growth media
- Peptides and digest maps
- Intact proteins and antibodies
- Light and heavy chain analysis
In his presentation, Mike noted that all these separations can be completed in less than three minutes and most samples require minimal, if any, sample preparation. Currently, Mike’s team is applying microfluidic CE-ESI technology to investigate broader bioanalytical assays including in the metabolomic and clinical fields.
What is next?
As former UNC student and GBMSDG President, Alessandra Ferzoco, mentioned during Mike’s introduction, he and his team are passionately leading an area that originally seemed impossible to some of the existing scientific community. Mike’s focus on developing microfluidic devices and coupling them with MS instruments is greatly benefitting the industry and we have incorporated many of these advances in the commercialization of our ZipChip. Thanks to the great work by Alessandra and the GBMSDG team in organizing another thought-provoking meeting. We eagerly await the next event!