A new technology developed at ETH Zurich will be extremely interesting for drug discovery and screening applications. The main feature of the technology is the extremely high sensitivity that will enable detection of attomole quantities in single cells in a novel high throughput method.
High-density micro-arrays for mass spectrometry (MAMS) enable rapid picolitre-volume aliquoting by moving a droplet over an array of hydrophilic spots on an otherwise omniphobic surface. After subsequent application of MALDI matrix, ultra-sensitive analysis of microscale samples, for example, single cells may be performed.
Molecular systems biology requires an analytical platform to study phenomena related to cell individuality and cell population heterogeneity that enables non-targeted molecular analysis of single cells. However, it faces hree major problems: (i) sample preparation, i.e. isolation of single cells, (ii) the required ultra-high sensitivity to detect the minute amount of metabolites in single cells (femto- to attomoles) and (iii) high-throughput capability (to achieve statistically meaningful results among other things).
A conductive support such as steel or transparent indium-tin oxide (ITO) is coated with an omniphobic layer (e.g. polysilazane). Then, by laser ablation, a dense pattern of hydrophilic spots is created with sizes of 30 – 300 μm and a spacing of several hundred micrometers (Fig. 1). The array may be labeled (by the laser) in order to identify individual spots. The recipient sites can be easily and reproducibly filled with picoliter volumes (containing few to single cells (Fig. 2) or any other compound of interest) by dragging a droplet over the platform.
Features & Benefits
- High throughput MS
- Unsupervised and very fast aliquoting of pico-litre volumes
- Extremely high sensivity: detection of attomole quantities of compounds (e.g. in single cells)
- Deposition of single cells
- Very low sample and reagent consumption
Fields of Application
- Drug discovery and screening applications
- High throughput single-cell analysis (Fig. 3), e.g. cancer and stem cell analysis
- High throughput combinatorial screening
- Collection of effluents from microscale capillaries/microcolumns or microfluidic devices for MS
- Calibration of surface analysis techniques
- Studies on the chemical communication within microbial cell populations, for example, the so-called ‘‘quorum sensing’’
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