Immunoassay tests are commonly used to diagnose a whole host of disease / medical conditions. In general the technology behind them relies on the manipulation of paramagnetic assay beads as analyte labels, as they are easy to manipulate magnetically, moving them through the assay process and concentrating them in a detection area. These beads have the unique property of being super-paramagnetic; they are only magnetic when placed in a very strong magnetic field (bias field), which is critical to their success as labels for analyte detection. These analytes/assay beads are usually captured and immobilised in a line, typically on a nitrocellulose strip or on a microfluidic strip deposition area.
Conventional assays detect and measure these analytes on their capture line or trap areas using optical instruments to measure reflectance, contrast, colour change or fluorescence emitted from the nanoparticle coating. However, a great deal of these analytes are not detected by the optical measuring device, resulting in poor accuracy, especially in POC devices where optical instrument quality is limited by cost and/or size.
While other devices are limited to imperfect optical detection, MIDS detects magnetically to a whole new level of accuracy: The MIDS patented technology utilises miniaturised highly sensitive custom built “Hall Effect” magnetic sensors embedded within a test strip as a Lab-On-Chip device. Hall Effect sensors are commonplace; to be found in virtually every electronic device from an alarm clock to a zip drive. They sense low levels of magnetic signature from magnetic device components. Immunoassay beads are paramagnetic, albeit on a much smaller scale: only in an adequately strong magnetic field will they behave magnetically.
The MIDS patented technology can separate the relatively large ambient magnetic field needed to induce the paramagnetic effect in the particles from the tiny, nano-Tesla aggregated signature of the assay beads themselves. A precisely located bespoke Hall effect sensor is then used to detect the aggregated paramagnetic signal.
Significant development work has been carried out, with quantitative testing conducted to determine the minimum numbers of assay beads that can be detected and to prove the linearity of detection signal to quantified bead numbers. MIDS Medical has been advised that a capability to detect below 200,000 assay beads and preferably less that 110,000 is required to support a high sensitivity troponin test in the context of the MIDS test strip.
Two widely available brands of paramagnetic beads have been tested, both of which are regarded as suitable for a high sensitivity troponin assay and having similar paramagnetic characteristics.
The MIDS limit of detection of both of these brands was seen on a reliable and repeatable basis at around 50,000 beads, with good signal linearity (required for accurate assay quantitation) at higher numbers. This number of beads is about four times better than the maximum advised threshold and therefore well within the range advised as suitable for a high sensitivity troponin assay.
MIDS Medical is now in a key phase of development to embody the MIDS nanomagnetic technology onto a microfluidic test strip incorporating a live, high sensitivity assay.
Our technology offers significant innovations:
The highest performing cardiac biomarker POC devices have a coefficient of variance in the 10% range at the 99th percentile (CV), although in reality they are unable to detect very low biomarker levels. By example, the POC device claiming to be the only one which conforms to tightened FDA guidance claims the device only achieves this CV at a detection of 36 ng /L. We believe our ability to measure the aggregated nano-Tesla paramagnetic signature of the particles themselves, when applied for example to HS cTn assays, will achieve > 5% CV on assays down to 2 ng cTn /l. Accuracy on this level matches state of the art central laboratory analyzers.
Our measurement technique should also require very low volumes of fluid sample, typically less than 5 μL (one small drop) for a single biomarker test using a finger stick blood sample on a microfluidic test strip for cTn- an industry leading low volume. This untreated finger stick sample innovation is material: competitor POC devices require, as a minimum, several times this whole blood volume. Blood volumes required by competitors are typically 100 – 200 µl, and can be as high as 2 ml (2000 µl). Many competitor blood samples also require pre-treatment (Heparain, EDTA). Our ability to use a very small & untreated sample allows us to contain an assay on a single easy to use lab-on chip strip; after the first touch of finger stick blood to the microfluidic strip the test is entirely automated.
We also expect to produce a quantitative cTn result much faster than any other POC device – within minutes and a quantitative, multiplexed test, again from a single finger stick sample, over a panel of 3 Cardiac biomarkers on a single test strip, in a few more minutes.
A successful development of MIDS Cardiac™ would validate the MIDS technology. We believe that MIDS can be applied to virtually any immunoassay test using magnetic assay beads, opening up enormous possibilities – a single device supporting multiple assay types on specific test strips of the same platform design.