High-Throughput DESI-MS Facility
Desorption electrospray ionization (DESI) is an ambient ionization method that allows direct analysis of complex mixtures and enables high-throughput (>1 Hz) mass spectrometry (MS) experimentation. This facility provides unique capabilities including reaction screening and optimization, accelerated nanoscale synthesis in microdroplets, analysis of biosamples, and label-free bioactivity assessments.
HT-DESI-MS
DESI is a 20-year-old technology that uses a charged solvent spray to impact on a surface, generating a thin film in which a microextraction event occurs, followed by the generation of splashed secondary microdroplets that carry the desorbed analytes to a mass spectrometer. The contactless nature of DESI allows for direct analysis of complex mixtures that are typically not MS-compatible (e.g. non-volatile buffers, non-liquid samples) without the need for sample workup.
Another key feature of DESI is the reaction acceleration phenomenon that takes place in the splashed secondary microdroplets, where organic reactions are accelerated up to a million times compared to bulk. This phenomenon is attributed to the special properties of the gas-liquid interface at the surface of very small droplets (i.e. large surface-to-volume ratio), including partial reagent solvation, strong interfacial electric fields, extreme pH, and the presence of highly reactive species.
Together, these features make DESI a unique alternative for HT experimentation as it is both a synthetic and an analytical tool. In combination with automated high-precision robotics and custom integration software, HT-DESI-MS provides throughputs better than 1 Hz with a wide variety of applications, spanning for instance early drug discovery.
Workflow
Currently, three generations of the HT-DESI-MS technology are available for both internal and external users. All the systems are located in a standard BSL2 facility within Purdue's Discovery Park. Further details on the instrumentation and capabilities of each generation can be found here.
- Gen 1.0: Developed within the DARPA Make-It program with in-house built integration.
- Gen 1.5: Extension of the first generation system with improved DESI technology for enhanced sensitivity and capabilities for ion mobility integration.
- Gen 2.0: Newest version of the platform developed within the NCATS ASPIRE initiative in collaboration with Waters Corporation and Hamilton Robotics. This system includes prototype state-of-art technology, including modules for HT microdroplet synthesis.
Regardless of the system generation, the general workflow for an experiment within the facility follows similar steps: (i) robotic fluid handling operations and array generation, (ii) HT-DESI-MS(/MS) screening, (iii) integrated data analysis. Screening results can also inform nanoscale compound collection (i.e. synthesis) for subsequent testing. Click here for further details.
Capabilities
Key features of the technology include:
- Capabilities for both fast chemical synthesis and analysis.
- Ultrahigh throughput for MS (>1 Hz) and MS/MS (~0.2 Hz) as well as nanoscale synthesis (hundreds of nanograms per minute).
- Accelerated microdroplet chemistry allows for reactions with no incubation time.
- Workup, surrogate, and label-free biological analysis and bioactivity assays.
- Minimal sample requirements (50 nL, typically few ng).
- Compatibility with a wide variety of solvents, as well as biological samples (bacteria, cell cultures, tissue, organoids, biofluids) and in vitro matrices (non-volatile buffers with high salt contents).
- High-density arrays with up to 6,144 samples or reactions per plate.
- Fully automated workflows including robotic fluid handling, array generation, transfer, and screening, as well as data analysis.
Here you can find further details on the system capabilities, including successful examples of a variety of applications, users and collaborators, as well as publications resulting from the use of this technology.