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 magnetic nanoparticles as analyte labels, as they are easy to manipulate magnetically, moving them through the assay process and concentrating them in a detection area. These particles 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/nanoparticles 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, as the analyte in biological fluids travels through the whole thickness of the test strip a high percentage (over 70%) 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 also detects magnetically, to a whole new level of accuracy: Like other devices, the MIDS patented technology not only uses a cost effective, bespoke sensor to measure optically, but crucially also 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 nanoparticles 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 paramagnetic signature of the particles themselves. A precisely located bespoke Hall effect sensor is then used to detect these tiny passing paramagnetic signatures.
Prior work undertaken by members of our technical team has successfully evidenced that a very low concentration of nanoparticles (less than 40nm size) in a 1% solution can be detected. This was achieved by using specially fabricated, packaged (the sensor being bonded within a protective resin) ultra-high sensitivity Hall effect sensors and creating a relatively strong external magnetic field (external bias field) which interacts with displaced magnetic nanoparticles during the immunoassay test. These fully packaged devices have successfully demonstrated that that we can detect the disturbance to this external bias magnetic field caused by 40nm particles allowing detection of magnetic fields at a few nano-Tesla levels. The result is a direct measurement of levels of antibodies present in the sample by measuring the magnetic signal of the immunoassay particles, rather than solely measuring the optical intensity of an aggregated group of particles, most of which are not detected. Work to date has been carried out on a relatively unsophisticated bench set up and with packaged sensors not optimally located at the detection site. As we optimize the MIDS technology we aim to achieve detection down to nanoparticles of 10nm; the result is expected to be outstanding accuracy in an easy to use POC test strip.
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 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 three 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 less than 8 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 nanoparticles, opening up enormous possibilities – a single device supporting multiple assay types on specific test strips of the same platform design.