Drug Discovery

Advancing Mass Spectrometry with Immediate Drop on Demand Technology (I.DOT)

Immediate Drop on Demand Technology (I.DOT) and Open-Port Sampling Interface (OPSI) are two innovative technologies that revolutionize mass spectrometry, offering high-throughput, precise, and non-contact sample handling for real-time analysis of challenging samples.


Mass spectrometry is a robust analytical tool in an assortment of scientific domains, including chemistry, biology, environmental science, and medicine. It has seen considerable improvements in sensitivity, resolution, and throughput throughout time. Over the years, advancements in mass spectrometry have significantly improved its sensitivity, resolution, and throughput. One such groundbreaking innovation is Immediate Drop on Demand Technology (I.DOT), a cutting-edge liquid handling system that has revolutionized sample preparation and data acquisition in Open-Port Sampling Interface (OPSI) mass spectrometry.  

A synergy: I.DOT and OPSI 

Immediate Drop on Demand Technology (I.DOT) is a liquid handling system that enables precise, non-contact dispensing of nanoliter to microliter volumes of liquids. These systems excel in delivering small liquid droplets with high precision, reducing sample consumption, and minimizing cross-contamination risks. I.DOT allows for highly accurate and reproducible delivery of samples, reagents, and standards directly onto the mass spectrometry target, eliminating the need for manual pipetting and reducing sample consumption.  

The Open-Port Sampling Interface (OPSI) is a revolutionary sample introduction approach that allows for direct, real-time sample analysis without any prior separation or extraction. OPSI employs an open atmospheric pressure intake through which samples are continually introduced, allowing for direct analysis of challenging mixtures.  

This dynamic duo has the potential to transform analytical capabilities by allowing fast and precise sample insertion and analysis. 

The I.DOT allows researchers to automate sample preparation, process large sample sets quickly, and increase data consistency in mass spectrometry techniques. For example:  

Boosting the efficacy of Mass Spectrometry sample preparation 

Sample preparation is a key step in mass spectrometry that can have a substantial impact on the quality and consistency of the results. I.DOT automates the accurate transfer of samples and reagents onto the mass spectrometry target, hence expediting the sample preparation workflow (Berkel et al, 2017 Furtwängler et al., 2022). Its non-contact dispensing reduces the possibility of cross-contamination, resulting in accurate and reproducible findings even with small sample amounts. Furthermore, I.DOT's high-throughput capabilities allow researchers to handle large numbers of samples quickly, hence accelerating up data acquisition and analysis. 

Improving Quantitative Analysis 

In quantitative mass spectrometry analysis, internal standards and calibration curves are frequently used. The accurate dispensing capabilities of I.DOT allow for the exact delivery of standard solutions, guaranteeing the creation of valid calibration curves. Moreover, I.DOT improves the accuracy and precision of quantitative mass spectrometry analysis by minimizing variability in sample preparation, making it particularly useful in the fields of Pharmacokinetics, Metabolomics and Lipidomics, Environmental and Forensic Applications.  

Performing Sustainable Experiments 

Conventional liquid handling techniques frequently call for substantial sample volumes, leading to higher consumption and the waste production. I.DOT's non-contact dispensing reduces sample utilization, which is especially beneficial for valuable or scarce samples. Researchers may save samples while acquiring high-quality mass spectrometry data by delivering precise nanoliter droplets, making I.DOT an environmentally friendly alternative. 

State of the Art

Screening enzyme libraries for modifying enzymes and identifying key domains required for improved activity is tedious and time consuming. Enzymatic biodegradation of polymers, such as polyamides (PA), has the potential to cost-effectively reduce plastic waste, but enhancements in degradation efficiency are needed. Recently, the combination of immediate drop on demand technology (I.DOT) liquid handling systems coupled with open port sampling interface-mass spectrometry (OPSI-MS) was employed for a high-throughput screening of PA6 and PA66 hydrolysis by 6-aminohexanoate-oligomer endohydrolase (nylon hydrolase, NylC). This I.DOT/OPSI-MS approach needed just less than 1 µL sample solution, a single sample was analyzed in as little as eight seconds and was suitable to 96-well plate layouts for automated processing (Fig. 1). This new methodology shall be used to evaluate the enzymatic hydrolysis of synthetic enzyme libraries, which will consist of thousands of individual samples. 

 Demonstration of I.DOTOPSI-MS technique used to screen enzyme library

Figure 1. The diagram represents the demonstration of I.DOT/OPSI-MS technique used to screen enzyme library. The bottom traces show ion chromatograms, with distinct colors indicating different samples. 


The integration of Immediate Drop on Demand Technology (I.DOT) liquid handling devices and Open-Port Sampling Interface (OPSI) mass spectrometry has established an entirely novel analytical paradigm. Researchers can now enjoy fast, precise, and non-contact sample handling while conducting real-time analysis of challenging samples. This remarkable synergy opens new opportunities in a variety of scientific disciplines, ranging from metabolomics and pharmaceutical research to environmental monitoring and forensics. As technology advances, the combination of I.DOT liquid handling with OPSI-mass spectrometry has the potential to promote breakthrough research and discoveries in the next years. 


Van Berkel GJ, Kertesz V, Boeltz H. Immediate drop on demand technology (I-DOT) coupled with mass spectrometry via an open port sampling interface. Bioanalysis. 2017 Nov;9(21):1667-1679. doi: 10.4155/bio-2017-0104. Epub 2017 Nov 2. PMID: 29095038. 

Furtwängler B, Üresin N, Motamedchaboki K, Huguet R, Lopez-Ferrer D, Zabrouskov V, Porse BT, Schoof EM. Real-Time Search-Assisted Acquisition on a Tribrid Mass Spectrometer Improves Coverage in Multiplexed Single-Cell Proteomics. Mol Cell Proteomics. 2022 Apr;21(4):100219. doi: 10.1016/j.mcpro.2022.100219. Epub 2022 Feb 25. PMID: 35219906; PMCID: PMC8961214.

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