eBook: New Frontiers in Infectious Disease Research - 21
available (methyl-CpG-based eukaryotic DNA depletion).
Poor and slow depletion can ultimately
affect the sensitivity of pathogen detection, particularly
when the pathogen DNA/RNA are present
in low amounts.
A novel host depletion method
Micronbrane Medical's patented Devin® Zwitterionic
Interface Ultra-Self-assemble Coating (ZISC)
fractionation filter fundamentally differs from other
host depletion methods. While a mechanical,
pre-extraction method, the Devin filter is simple,
utilizing a familiar wet lab procedure. In many tests
and studies, the Devin filter consistently removes
greater than 99% of host nucleated cells of up to
10 mL of biological fluid within five minutes. Most
importantly, the Devin filter reduces the presence
of host interference while increasing the proportion
of microbial pathogen DNA in human blood
samples 10-1,000-fold.9
Zwitterionic networks have higher stability in
complex mediums and provide strong hydration
to the membrane, which acts as an energetic barrier
against adsorption and biofouling by proteins
and blood cells. The Devin filter removes nucleated
cells from whole blood, plasma, cerebrospinal,
bronchoalveolar lavage, vitreous humor or other
fluids, while ensuring a high microbial passing
efficiency due to its unique pore size. In fact, the
pore size of the Devin filter is 15-20 μm, which is
larger than most of the human cells enhancing
the ability of the microorganism to pass through
the filter unaltered.
How effective host depletion
increases sensitivity
When the Devin filter was tested with simulated
samples (whole blood from healthy donors spiked
with 104
genome copies/mL spike-in control), results
show the increased ratio of microbial DNA and
decreased the ratio of host DNA results by various
downstream detection methods including, qPCR,
NGS and nanopore sequencing (Figure 4), comparing
to the other depletion methods discussed
above and illustrated in Figure 2.
A recent study conducted at Taipei Veterans General
Hospital showed that Micronbrane Medical's
Devin filter and a genomic DNA (gDNA) based
workflow, the Pathogen Real-Time Identification
by Sequencing (PaRTI-Seq™), provided an efficient
and accurate alternative to blood culture in identifying
pathogens in patients with suspected sepsis.
Figure 3. The Devin fractionation filter method of action
The PaRTI-Seq assay achieved higher positivity
rates (82%) compared to mNGS without a filter
(56%) or blood cultures (24%) and delivered results
within 24 hours. Moreover, the gDNA-based PaRTI-Seq
assay performed even better than cell-free
21
https://www.medrxiv.org/content/10.1101/2023.03.28.23287867v1
eBook: New Frontiers in Infectious Disease Research
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