APPLICATIONS OF TECHNOLOGY:
- In-vitro diagnostics
- Electrospray ionization mass spectrometry (ESI-MS), chromatography, microscopy, single cell omics, microfluidics
- Biopharmaceutical R & D
- Lab-on-a-chip analysis
- Environmental monitoring
- Integrated on-chip imaging and liquid chromatography functions
- Robust and scalable silicon fabrication
- High sensitivity, high throughput, multiplexing
- Improved reproducibility for parallel analysis
- Uses small volumes of biospecimens
Berkeley Lab scientist Daojing Wang and colleagues have developed an integrated microfluidic device to separate, image, and deliver biological samples into automated electrospray ionization mass spectrometry (ESI-MS) systems. This design builds upon the circular-shaped Multinozzle Emitter Array (MEA) chip previously developed by the Berkeley Lab team, but now integrates onto this silicon-based platform a microfluidic liquid chromatography (LC) system and a network of tiny glass portals for microcopy-based imaging.
These new functions are performed as multiple analyte samples are piped to entry points at the center of the platform, routed through separate microfluidic channels, and delivered to 24 electrospray emitters arrayed on the circumference of the MEA chip. The emitters can deposit samples sequentially into the ion cone of an ESI-MS spectrometer. The micro-fabricated emitters feature a sharpened tip design developed by the Berkeley Lab team to maintain, throughout the silicon platform, an electric field high enough to overcome charge-charge interactions that would otherwise become problematic as the number of nozzles increases.
The multiple LC channels, etched within layers of the MEA chip, contain built-in frits and perform chromatography using slurry-packed C18 beads or polymeric monoliths. The integrated imaging is accomplished using a thin glass layer, which provides clear views of the device for real-time microscopic monitoring of sample manipulation and processing. The design facilitates implementation of multiple LC functions for simultaneous, multiplexed analyses of target analytes.
Unlike other integrated electrospray systems, which deliver single samples to mass spectrometers, the circular MEA lab-on-a-chip can quickly deliver multiple samples sequentially — addressing a costly bottleneck of low throughput in present day MS analysis and creating a pathway for further integration of microfluidic lab-on-a-chip. Built with fabrication techniques developed for the semiconductor industry, the next-generation MEA chip is readily scalable for mass production and adaptable to high-speed robotically controlled systems. This combination of chromatographic and microscopic analysis of samples linked to high-throughput spectrometry can be used to profile large numbers of individual cells in a cost-effective manner.
DEVELOPMENT STAGE: Bench-scale prototype
STATUS: Patent pending. Available for licensing or collaborative research.
FOR MORE INFORMATION:Mao, P., Gomez-Sjoberg, R., Wang, D. “Multinozzle Emitter Array Chips for Small-volume Proteomics,” Analytical Chemistry 2013, Vol. 85, 816-819.
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REFERENCE NUMBER: IB-3303