Both partners are global leaders in scientific instrumentation, specializing in advanced analytical solutions. By combining Scienion precision single cell handling and sample preparation systems with either Bruker or Thermo Fisher Scientific’s high end mass spectrometry technology, ultra-sensitive single-cell proteomics (SCP) workflows are offered.
The Challenge
To overcome the key bottlenecks in the field – such as sample loss, workflow complexity, and limited sensitivity – and to unlock new opportunities in biomedical research, drug discovery, and personalized medicine by creating a high-throughput, ultra-sensitive single-cell proteomics workflow.
-
- Low sensitivity of Mass Spectrometry: Traditional MS systems struggled to detect and quantify proteins from the tiny amounts present in single cells
-
- Sample loss during preparation: Manual pipetting and liquid transfer steps often led to significant sample loss, especially critical at single-cell scale
-
- Reproducibility and throughput: SCP workflows were often low-throughput and inconsistent, limiting scalability and statistical power
-
- Complexity of workflow setup: SCP required expertise in multiple instruments and software, making adoption difficult
The Solution
Scienion has joined forces with Bruker and Thermo Fisher Scientific respectively to develop fully integrated solution workflows that revolutionizes single cell proteomics by combining ultra-sensitive mass spectrometry with automated end-to-end single cell sample preparation.
These partnerships enable researchers to analyze thousands of proteins from individual cells with unprecedented throughput, reproducibility, and sensitivity, scaling up to more than 100 single cells per day.
Infographic showcasing the Single-Cell Proteomics workflow. Further details on the workflow and key process considerations are provided below.
The Impact
The partners have jointly delivered a next-generation single cell proteomics solution that addresses critical market needs in precision medicine and life sciences.
Just as single cell transcriptomics has revolutionized biology by revealing the complexity and diversity of individual cells, single cell proteomics is now emerging as a key technology to complement and extend these insights.
These collaborations unlock new commercial and research opportunities by:
-
- Minimal sample loss by automated sample preparation: integrating all sample preparation steps into a single instrument and no manual pipetting
-
- Seamless compatibility: Integrated LC-MS ecosystem
-
- Ultra-sensitive detection: >4,500 protein groups per single cell
-
- High throughput: Up to more than 100 single cells/day
-
- High reproducibility: Robust quantification across replicates
-
- Commercial agreement: Co-distributed, bundled solutions tailored for pharmaceutical and academic labs expand accessibility and adoption
Together, these advancements position the solution as a powerful enabler for high-impact applications in biomedical research, drug development, and personalized healthcare.
Single Cell Proteomics Workflow in Detail
1. Reagent Dispensing
-
- A precise nanoliter amount of master mix is dispensed using the cellenONE system into proprietary nanowell chips (proteoCHIP product line) or standard microwell plates.
-
- This master mix is composed of a mild detergent for cell lysis and enzymes for protein digestion into peptide fragments.
-
- A precise and accurate control of the nanoliter volume dispensed is crucial to ensure efficient and reproducible reactions while avoiding excess reagent usage and thereby reducing both costs and chemical waste.
- A precise and accurate control of the nanoliter volume dispensed is crucial to ensure efficient and reproducible reactions while avoiding excess reagent usage and thereby reducing both costs and chemical waste.
2. Cell Isolation
-
- A cell suspension is loaded into the cellenONE system and cell isolation is undertaken.
-
- Thanks to its image-based cell selection, cellenONE’s users can select cells of interest based on various criteria (size, morphology, fluorescent markers) and have the possibility after isolation to review images of each cell isolated which provides an additional quality control which no other platform offers.
-
- In SCP workflows most wells are loaded with exactly one cell per well and a few wells contain accurate number of cells per well (e.g. 5, 20, 100) to be used as libraries for improved protein identification.
-
- Highly precise single cell positioning is crucial when working with minute volumes and nanowell. cellenONE precision and accuracy enable users to work with any nanowell formats.
3. Incubation
-
- During incubation, cells are lysed to release their protein content. Proteins are then digested into peptide fragments for bottom-up mass spectrometry analyses.
-
- Incubation is a critical step in SCP sample preparation. Accurate humidity, temperature and rehydration controls provided by cellenONE are crucial to prevent evaporation of the nanoliter volume contained in each well during the 2 hours of incubation at 50°C.
4. Transfer to LC-MS (Liquid Chromatography–Mass Spectrometry)
-
- Prior transfer to LC-MS, the nanoliter sample volume contained in each well is diluted using the cellenONE to allow subsequent direct injection in the liquid chromatography.
-
- The nanowell substrate or microplate containing the diluted sample is then transferred to the autosampler of the LC-MS system of choice to allow direct sample injection.
-
- To facilitate the transfer between instruments, it is important that the plate format is directly compatible with the LC system. This prevents any manual pipetting transfer, which can lead to peptide loss due to adsorption in pipette tips.
-
- The clever design of proprietary consumables and the ability to process samples in standard formats (both offered by cellenONE) enhance ease of use and facilitate seamless sample transfer to other instruments.
With cellenONE X1 Neo and its associated proteoCHIP consumables range, Scienion offers the only complete workflow for single cell proteomic sample preparation integrated into a single instrument available today on the market.
