The Liquid Biopsy Problem:

Insufficient yield of analytes lowers assay sensitivity often resulting in QNS and other errors

nRichDX delivers more cfDNA, cfRNA,

and circulating cell-free nucleic acids

Circulating cell-free DNA (cfDNA) is extremely rare, especially in early stages of cancer detection. Many competing sample prep systems were originally designed for applications that had plentiful targets in small samples (100 μl - 5 mL), not for the enrichment of cfDNA from liquid biopsies.

These methods are unable to achieve sufficient yields to detect the low allele frequency rates required for liquid biopsy testing, making them ineffective as an early detection diagnostic tool.

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Other Methods are Part of the Problem

They use yield-lowering procedures such as sample transfers, pre-extraction sample volume concentration, re-elution, and pooling steps

  • Sample Transfers - moving the sample from plasticware to plasticware during the extraction protocol, leaving small amounts of material behind with each sample transfer - including targeted rare analytes
  • Pre-extraction Sample Volume Concentration - Reducing the input sample volume to accommodate inherent volume limitations of the method
  • Re-elution of the extraction eluate - attempting to increase yield of analyte by passing the eluted sample over the extraction matrix repeatedly to boost yield of rare analytes
  • Pooling steps - extracting the same sample using multiple extractions and combining the eluates, which may require subsequent eluate volume concentration

 

Other methods, including automated methods, are inherently sample-volume limited and must use one or more of the above yield-lowering schemes to extract from volumes greater than 5 mL - 10 mL. These methods were not specifically engineered for extraction of rare analytes such as ctDNA and ctRNA which often leads to lower yields. Lower yields of analytes in the assay lowers assay sensitivity and limit of detection and may result in quantity not sufficient (QNS) and other errors.

The simple math

Yield is a function of sample volume and

recovery rate.

simple-math

Accuracy of allele detection depends on a sufficiently high cfDNA input, and optimal input is a simple function of sample volume and recovery rate. Competing sample prep systems are lacking in both volume and recovery rate, and therefore don’t produce sufficient yield to ensure a high probability of allele detection.

Volume matters more than recovery rate

High efficiency alone is not enough. A larger volume of starting material directly impacts the success of downstream tests, making it possible to detect very early stage cancers by liquid biopsy

In order to achieve a 99.99% chance of cfDNA detection at an allele frequency of 0.05%, you'll need at least 83ng of cfDNA in your assay†. Even with 100% efficiency, you won't be able to get 83ng out of 4ml of sample. To increase cfDNA yield, you’ll need to increase both sample volume and extraction efficiency

This can be accomplished using nRichDX’s high-efficiency Revolution System, which permits single-cartridge processing of sample volumes from 1 mL to 20 mL.

Competitors have neither the ability to process large sample volumes nor the extraction efficiency to achieve the high cfDNA yields needed to ensure reliable detection.

† Nature Communications Volume 8, Article number: 15086 (2017)

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The Liquid Biopsy Solution:

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Revolution Sample Prep Systems

Automation for the nRicher Cartridge

The nRichDX Revolution Plus Sample Prep System

Extraction of up to 12 samples per run in a semi-automated workflow

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The nRichDX Revolution Pro Sample Prep System

Scalable extraction of up to 24 samples per run in an automated workflow

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Industry-leading yield

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nRichDX has the widest sample input range of any system, from 1 to 20 mL; several times more than from competing technologies (500 µl - 4 mL).

A Growing Range of Liquid Biopsy Samples Types and Applications

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The Revolution Sample Prep System

The solution for insufficient liquid biopsy analyte yield

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