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BiosparQ Developing MALDI System for Microbe Identification Directly From Patient Samples

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NEW YORK (360Dx) – Microbiology firm BiosparQ is developing a MALDI-based system that can identify bacterial infections directly from patient samples without the need for culturing.

The Leiden, Netherlands-based company is currently evaluating the technology's usefulness for assessing urinary tract infections with researchers at Amsterdam University Hospital and aims to launch a CE-IVD-marked instrument for UTI detection in 2021, said René Parchen, the company's chief technology officer.

MALDI-based instruments have made major inroads into the clinical microbiology market over the last decade, with Bruker's MALDI Biotyper and bioMérieux's VITEK MS platforms becoming standard equipment in large clinical microbiology labs in the US and Europe. The systems have seen quick uptake due to their relative ease of use and their ability to provide results much more quickly than traditional biochemical assays and a lower cost than many nucleic acid based tests.

These MALDI-based systems identify microbes by matching the protein profiles of sample organisms generated via MALDI mass spec to profiles contained in proprietary databases. They offer faster turnaround time than traditional microbial ID approaches, but they still require culturing of samples to obtain isolates for mass spec analysis. This can add a day or more to the overall turnaround time. It can also present challenges in the case of organisms that are difficult to culture.

These issues have led researchers to explore whether direct mass spec analysis of patient samples might be possible. Several groups including the BiosparQ team have put forth potential approaches to performing such assays, but none have made it into widespread clinical use yet.

The BiosparQ approach is based on what the company calls its DigiTof technology, a combination of sample prep and MALDI mass spec that allows clinicians to isolate single bacterial cells from patient samples and analyze them sequentially in a MALDI instrument. As with the Bruker and bioMérieux systems, spectra generated by the MALDI analysis are then compared to organism databases allowing for identification of the bacteria in a given sample.

The DigiTof approach involves isolating the bacterial cells from a sample via centrifugation or other method then making a suspension of them in a proprietary solvent that also contains MALDI matrix material. The suspension is then divided into small droplets each containing either no bacterial cell or a single bacterial cell. The solvent then evaporates, leaving the single bacterial cell and MALDI matrix, which is then introduced to the MALDI instrument and analyzed. According to Parchen, the entire process takes around five to 10 minutes.

While single-cell mass spec analyses are typically not as sensitive as bulk-level analyses, Parchen said that he and his colleagues see similar sets of protein and peptide peaks using the DigiTof system as they observe for the same organisms with the Bruker or bioMériex platforms.

He said the company is aiming for sensitivity and specificity of 95 percent for its UTI assay, which he noted compares favorably to existing testing methods like urinalysis strips. Additionally, given that roughly 50 percent of UTIs fail to culture, a rapid and high-performance direct detection approach could be useful.

Implementation of the instrument presents a potential challenge given that MALDI mass spec is not well suited to the sort of point-of-care environments like doctor's offices, where UTI patients are typically seen, and sending out samples to a central lab would negate much of the system's advantage in turnaround time.

Parchen said the company was exploring an option where it would place the instrument in a facility central to a number of primary care offices, which could share the system between them. Patients with suspected UTIs could go to this facility, provide a urine sample, and receive their results in around 15 minutes, he said.

In addition to UTIs, BiosparQ is investigating whether the system could be effective for identifying other kinds of infections. Much of this will depend on whether the sample prep method will be able to isolate a sufficient number of single bacterial cells for analysis, which Parchen noted could prove challenging in the case of, for instance, blood stream infections, though he said that it was feasible in theory given that the system is able to make reliable identifications based on the analysis of as few as 20 to 100 cells.

The DigiTOF technology was originally developed by researchers at Delft University of Technology and the Dutch Contract Research Organization as part of a biodefense project funded by the US Department of Defense and the Dutch Ministry of Defense. The company launched in 2009 and closed a Series A funding round in 2012, shifting its focus from military to medical applications. It closed a Series B round in 2016.

BiosparQ currently has 15 employees and is funded by private investors and an Innovation Credit from the Dutch government.

Parchen said the company has received interest from Bruker and bioMérieux regarding its technology but that it is not involved in any formal discussions or collaborations. Because the DigiTOF system is designed for ionization of single cells as they fly through the mass spec, the company had to develop its own MALDI system, meaning, Parchen said, that "it wouldn't make much sense" to try to combine BiosparQ's sample prep with an existing MALDI microbiology platform.

The company is also developing its own spectral libraries for identifying microorganisms based on mass spec data. Its UTI library currently contains around 20 species, Parchen said.

Another company with a foot in the mass spec-based direct detection game is Waters, which owns the rapid evaporative ionization mass spectrometry (REIMS) technology developed by Imperial College London researcher Zoltan Takats, whose lab has demonstrated its ability to identify bacterial directly from tissue samples. 

In January, a team led by researchers at the IHU Méditerranée Infection published a study in the Journal of Clinical Microbiology using a MALDI Biotyper for direction identification of bacteria in UTIs. Using a centrifugation-based sample prep technique with a standard MALDI Biotyper workflow and custom-built database, the researchers were able to correctly diagnose 90 percent of 500 infected monobacterial samples.