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Technology Offer High-Throughput Multiplexing Chromatography File no.: MI0042-4680-LC-WA Background One of the remaining challenges in modern chromatography is to analyze large numbers of samples produced by screening of parallelized chemical reactors or combinatorial compound libraries. Moreover investigation and monitoring of fast reactions requires high temporal resolution. One approach to meet these demands is the combination of information and subsequent mathematical deconvolution of the overlapping signals (multiplexing). Multiplexing techniques are already widely used in spectroscopy (FT-NMR, FT-IR) and mass spectrometry (FT-ICR-MS, HT- TOF-MS). Significant increase in signal-to-noise ratio and reduction of data acquisition time makes the use of these techniques for high-throughput chromatography applications desirable. Technology For multiplexing chromatography samples are injected according to a pseudo-random binary modulation sequence based on Hadamard matrices. Deconvolution of the raw chromatographic data by Hadamard transformation yields the chromatogram of the injected sample. First HPLC applications were done on a conventional Agilent Infinity 1260 HPLC system that was modified by a software macro which creates a list of instructions for the autosampler, allowing highly stable and reproducible sample injections (variation of peak areas 0.5 %RSD). Minimum injection interval supported for Agilent high performance autosamplers is Δt = 18 s; maximum sequence length is 11-bit (211-1 = 2047 elements). The generation of a modulation sequence, the macro and the Hadamard transformation are performed by a program written in Delphi. Using structured modulation sequences analysis of 100 samples/hour is possible independent of sample complexity and retention time of the analytes. This leads to a significant increase in sample-throughput. By applying sequences of up to 2047 elements (11-bit) the signal-to-noise ratio of trace amounts of samples could be significantly enhanced. Max-Planck-Innovation GmbH Amalienstr. 33 80799 Munich Germany Phone: +49 (89) 29 09 19 - 0 Fax: +49 (89) 29 09 19 - 99 [email protected] www.max-planck-innovation.de Contact Dr. Lars Cuypers Phone: +49 (89) 29 09 19 - 21 [email protected]

Techoffer MI0042-4680 - Hadamard Transform Multiplexing ... · PDF fileTechnology Offer High-Throughput Multiplexing Chromatography File no.: MI0042-4680-LC-WA Background One of the

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Page 1: Techoffer MI0042-4680 - Hadamard Transform Multiplexing ... · PDF fileTechnology Offer High-Throughput Multiplexing Chromatography File no.: MI0042-4680-LC-WA Background One of the

Technology Offer High-Throughput Multiplexing Chromatography File no.: MI0042-4680-LC-WA Background One of the remaining challenges in modern chromatography is to analyze large numbers of samples produced by screening of parallelized chemical reactors or combinatorial compound libraries. Moreover investigation and monitoring of fast reactions requires high temporal resolution. One approach to meet these demands is the combination of information and subsequent mathematical deconvolution of the overlapping signals (multiplexing). Multiplexing techniques are already widely used in spectroscopy (FT-NMR, FT-IR) and mass spectrometry (FT-ICR-MS, HT-TOF-MS). Significant increase in signal-to-noise ratio and reduction of data acquisition time makes the use of these techniques for high-throughput chromatography applications desirable. Technology For multiplexing chromatography samples are injected according to a pseudo-random binary modulation sequence based on Hadamard matrices. Deconvolution of the raw chromatographic data by Hadamard transformation yields the chromatogram of the injected sample.

First HPLC applications were done on a conventional Agilent Infinity 1260 HPLC system that was modified by a software macro which creates a list of instructions for the autosampler, allowing highly stable and reproducible sample injections (variation of peak areas 0.5 %RSD). Minimum injection interval supported for Agilent high performance autosamplers is Δt = 18 s; maximum sequence length is 11-bit (211-1 = 2047 elements). The generation of a modulation sequence, the macro and the Hadamard transformation are performed by a program written in Delphi. Using structured modulation sequences analysis of 100 samples/hour is possible independent of sample complexity and retention time of the analytes. This leads to a significant increase in sample-throughput. By applying sequences of up to 2047 elements (11-bit) the signal-to-noise ratio of trace amounts of samples could be significantly enhanced.

Max-Planck-Innovation GmbH Amalienstr. 33 80799 Munich Germany Phone: +49 (89) 29 09 19 - 0 Fax: +49 (89) 29 09 19 - 99 [email protected] www.max-planck-innovation.de

Contact Dr. Lars Cuypers Phone: +49 (89) 29 09 19 - 21 [email protected]

Page 2: Techoffer MI0042-4680 - Hadamard Transform Multiplexing ... · PDF fileTechnology Offer High-Throughput Multiplexing Chromatography File no.: MI0042-4680-LC-WA Background One of the

A lot of know how related to the implementation of the technology on different chromatography systems and the necessary software solutions are available in addition to the patent license. Advantages for HPLC applications

• robust multiplexing technique combining o the advantages of multiplexing and o the high stability and reliability of conventional HPLC

• Hadamard encoding is applied by simple software modification o no sophisticated instrumentation is necessary

• signal-to-noise ratio of complex sample mixtures is enhanced up to 15-fold • using structured injection sequences up to 100 samples/h can be analyzed

o sample-throughput of HPLC is increased greatly • the method can easily be combined with detection techniques such as

o mass spectrometry o fluorescence detection o refractive index detection

Literature

• O. Trapp: "Boosting the Throughput of Separation Techniques by Multiplexing", Angew. Chem. Int. Ed. 2007, 46, 5609 –5613

• O. Trapp: "Gas chromatographic high-throughput screening techniques in catalysis", J. Chromatogr. A 1184 (2008) 160–190

• O. Trapp, A. Siegle: "High-Throughput Multiplexing Gas Chromatography", Chem. Ing. Tech. 2014, 86, No. 7, 1044–1051

Patent Information

• DE2005050114, Priority Date Oct. 18, 2005 • PCT application WO07045224 filed Oct. 17, 2006 - nationalized in EP, US, JP

o EP patent application under examination o US8297135B2 granted Oct. 30, 2012 o JP528996B2 granted Jul. 14, 2013