Category: Automation and High-Throughput Technologies
We present the development of direct acoustic mist ionization (AMI) mass spectrometry to deliver label-free, high-throughput screening (HTS). We use a customized Labcyte Echo® acoustic liquid handler to eject electrically charged droplets directly from a 384-well assay plate into a custom transfer interface where desolvation and ion generation occur in an electro-spray ionization (ESI) mode. The resulting ions are detected by a Waters MS instrument. The liquid chromatographic (LC) separation step is eliminated by optimization and redesign of sample buffers to improve sensitivity and minimize ion suppression while maintaining biological activity. We have successfully demonstrated AMI for sub-second sample processing of label-free biochemical assays.1
An Echo acoustic liquid handler has been modified to eject microdroplet sprays at rates of up to 1500 transfer-events-per-second directly from sample wells of a standard Labcyte 384-well microplate. A custom XY stage has been integrated to move the plate and position wells over the piezoelectric transducer for acoustic sampling. The microdroplets ejected may be charged using an electric field and are collected at the entrance aperture of a transfer tube interface. Using this integrated AMI-MS platform, assays may be developed and executed by dispensing sample directly from the microplate into the API source of the mass spectrometer.
Here we present the capability of AMI to eject and ionize organic samples (50% and 100% v/v acetonitrile) into a mass spectrometer to enable sub-second analysis. We demonstrate a linearity range of about 4 orders of magnitude for simple organic solutions , as well as a sensitivity advantage compared to purely aqueous samples. Across replicate samples of simple organic solutions, we have achieved good sensitivity, 15 pM LoD and 40 pM LoQ, and a Coefficient of Variation as low as 14% across a 384-well plate . The addition of pure and aqueous mixtures of acetonitrile expands capabilities of AMI for high throughput, label-free and low sample consumption assays.
1. J Lab Autom. 2016, 21(1), 19-26.
Deepshikha Angrish– Staff Scientist, Labcyte, Inc., San Jose, CA
San Jose, CA
Deepshikha Angrish is a Synthetic Organic Chemist by training. She holds expertise in Automation and High Throughput Reaction Screening. At Labcyte, she is working as a Staff Scientist on Acoustic Mist Ionization platform for its applications in High Throughput Mass Spectrometry.