Matrix-Assisted Laser Desorption/Ionization Imaging - Mass Spectrometry (MALDI-MS): revolutionizing scientific research by automating sample preparation.
Mass spectrometry (MS) is a powerful analytical technique that has revolutionized the way scientists study and understand organic compounds. It has the remarkable ability to perform label-free detection of analytes (as opposed to classic microscopy imaging), and more importantly, have the capability to monitor thousands of molecules in a single experiment. MS enables researchers to determine the molecular mass and chemical structure of various analytes within a sample, ranging from proteins in proteomic research to genetic targets in genomics. Mass spectrometry remarkable power and diverse applicability provide unique opportunities for supporting drug discovery and development efforts throughout the drug development life cycle, including drug discovery, development, quality monitoring and manufacturing.
As part of the Hamilton family, BioFluidix provides the most precise and accurate liquid dispenser technology. With unique solutions tailored to your application, you can automate your workflows. Liquid-independent, contactless, production-optimized, and limitless. Precise sample preparation or reproducible matrix application are just a few example applications of our flexible non-contact dispensing technology.
Mass spectrometry begins with the process of ionization, in which the molecules composing the sample are converted into ions. The specific method used for ionization can vary, depending on the analytes and chosen MS analysis technique.
In this exploration of MS and automation, we will focus on Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS). This soft ionization method is suitable for analyzing large biomolecules like proteins, peptides, nucleic acids, and other high-molecular-weight compounds, and is widely used in proteomics and biomolecular research. MALDI-MS has become increasingly important in the last decades due to its significant impact on scientific research (eg, tissue imaging) and clinical diagnostics.
Efficient sample preparation is a crucial step in performing MALDI-MS projects. Samples are prepared by co-crystallizing them with a matrix, typically composed of small acidic molecules. The matrix solution mixed with the sample is spotted or sprayed onto a MALDI plate, which facilitates the crystallization of the sample-matrix mixture. MALDI plates come in various formats, including stainless steel plates with sample spots or wells, and are specifically designed to accommodate different types of samples. The matrix absorbs ultraviolet light (emitted by a laser) and transforms it into heat energy, resulting in the desorption and ionization of the sample. Therefore, when a laser beam is directed at these matrix-embedded samples, the energy absorbed by the matrix causes the analyte to vaporize and become ionized.
Once the sample is ionized, the generated ions are accelerated using an electric field. This ensures that all ions, irrespective of their size, have the same kinetic energy as they enter the TOF (Time-of-Flight) mass analyzer.
In the TOF mass analyzer, ions travel down a "flight tube." The time taken for ions to traverse this tube is measured. Lighter ions (or ions with higher charge) will reach the detector faster than heavier ions. Because all ions started with the same kinetic energy, the time taken (or "time of flight") to reach the detector will be directly proportional to the square root of their mass-to-charge ratio (m/z).
At the end of the flight tube, there is a detector that measures the time each ion takes to arrive. This information is used to determine the m/z ratio for each ion.
A mass spectrum is a plot with m/z values on the x-axis and ion abundance (intensity) on the y-axis. Peaks on a mass spectrum represent ions of different m/z ratios, with the height of each peak indicating the relative abundance of that ion. This technique can provide vital information about the molecular weight of compounds in a sample. In some cases, when a molecule is fragmented into several ions, the spectrum can also offer clues about the molecule's structure.
COMMON APPLICATIONS OF MALDI-TOF MS
Biomarker Detection for Disease Diagnosis
Proteomics and Metabolomics
Understanding MALDI-TOF MS challenges
MALDI-TOF MS, is a cutting-edge technology that has significantly advanced the field of analytical chemistry.
This technique is used for the analysis of large biomolecules, such as proteins, peptides, nucleic acids, and other high-molecular-weight compounds. Sample preparation is a crucial step to ensure accurate and reproducible results. The precise dosing technologies of BioFluidix support scientific researchers in optimally leveraging the advantages of MALDI-TOF MS. With flexible applicability, precise and reliable dosing of samples and matrices, and intuitive programming of devices, substrate independent processes can be developed quickly and effectively.
MASS SPECTOMETRY IMAGING: MSI
When the analysis requires the spatial resolution on a tissue of interest, the matrix can be applied directly onto biological specimen (generally a tissue section of a biological sample). Similarly, the matrix helps desorb and ionize the analyte molecules when struck by the laser. Two methods exist to prepare a sample for imaging. One method spreads the matrix all over the sample, which is flexible for capturing detailed images but might cause molecules to spread sideways more than desired. The other method uses automated spotters to coat the sample with evenly spaced droplets, and the distance between these droplets determines the image resolution. The efficiency of the spotter determines how accurately molecules can be traced back to their specific originating cells, akin to identifying specific locations on a map. This process involves converting mass spectrometry data into visual images, allowing for the detailed mapping of individual molecules within the tissue.
The precision of sample preparation is a cornerstone of successful MALDI analysis. Enhancing sample preparation demands specialized technologies and systems capable of precise and contamination-free dispensing of small liquid volumes onto various substrates, achieved by pre-storing specific reagents. This precision and reproducibility are essential for improving the sample preparation process.
To fully harness the potential of mass spectrometry imaging, automation of sample preparation becomes essential. This is where BioFluidix and the BioSpot® automation platform steps in, offering numerous advantages that streamline the process and improve the quality of results.
BIOFLUIDIX: PIONEERING PRECISION SOLUTIONS FOR MALDI SAMPLE PREPARATION:
BioFluidix stands at the forefront of precision solutions, offering groundbreaking technologies like the PipeJet® nanodispenser and the BioSpot® workstation. These innovations are not just technological marvels; they are instrumental in overcoming significant challenges in sample preparation.
MALDI sample preparation
SCIENTIFIC RESEARCH ENABLED BY BIOFLUIDIX TECHNOLOGY
Scientists across both academia and the biopharmaceutical industry trust BioFluidix technologies to propel their research forward. Below, we've highlighted selected examples showcasing how our customers leverage the versatility and power of BioFluidix technologies, particularly in the realm of mass spectrometry imaging (MSI).
In the subsequent section, we delve into specific research studies and publications that have benefited from BioFluidix technology to enhance their investigations.
Dannhorn et al. 2021
This study presents a decontamination method using ultraviolet-C (UV-C) light to safely eliminate infectious pathogens in clinical tissue samples for mass spectrometry imaging while preserving analyte distributions. The authors found that lower UV-C doses maintain pathogen inactivation with less damage to the tissue's metabolome and enable the analysis of endogenous metabolite distributions and even the abundance of a specific inhibitor in decontaminated biopsies.
Luptáková et al. 2021
The aim of the study is to quantitatively and visually assess drug transport across the region-specific blood-brain barrier (BBB) using in vivo and in vitro neuropharmacokinetic investigations with mass spectrometry imaging. This approach enables the differentiation of regional and subregional BBB transport characteristics in small brain regions, providing valuable insights for molecular psychiatrists in understanding regional target-site exposure and decision-making.
Hamm et al. 2022
The study aimed to assess the in vivo effects of pharmacological inhibition of the receptor tyrosine kinase MERTK using a multi-modal imaging platform. The study employed mass spectrometry imaging (MSI) to characterize the spatial distribution of the MERTK inhibitor AZ14145845 in the eye. It provides a strategy to investigate the preclinical toxicity of MERTK inhibitors and potentially other chemotypes.
BIOSPOT® AUTOMATION PLATFORM: ELEVATING MALDI-TOF MS
BioFluidix's BioSpot® automation platform is a game-changer when combined with MALDI-TOF MS, enabling scientists to streamline workflows, enhance precision, reduce costs, and achieve consistently reliable results. This dynamic synergy offers unprecedented possibilities across various scientific fields, from microbiology to drug discovery and beyond. With BioSpot® at the forefront of sample preparation, precision becomes paramount.
Our liquid-independent, contactless, and production-optimized dispensing technology delivers a level of accuracy that forms the bedrock of scientific research and diagnostics. It ensures that even the tiniest liquid volumes are dosed with impeccable reliability.
Beyond simply enhancing data quality, our solutions also offer versatility, from straightforward dosing tasks to highly complex, automated systems.
As part of the Hamilton family, BioFluidix is dedicated to driving the benefits of MALDI-TOF MS, resulting in better care for patients and a brighter future for researchers.
Next-generation dispensing systems are pivotal in advancing mass spectrometry, enabling precise, efficient, and error-free sample preparation while optimizing medical processes, ultimately saving time and costs.
Our customized solutions, developed in close collaboration with customers, empower them to achieve progress more swiftly and efficiently. In the world of liquid dosing, BioFluidix is synonymous with precision and limitless potential.