The Unmet Medical Need

When a suspected heart incident occurs, usually after chest pain complaint, emergency responders turn to an immediate ECG, complemented by blood tests for the cardiac markers troponin I or T, to diagnose AMI. The troponin element of diagnosis is problematic: While troponin levels from damaged heart muscle rise rapidly after AMI and become easy to detect, the challenge is early detection when levels are very low. Because of this, where possible, medics turn to high sensitivity tests. These high sensitivity troponin tests have been in use in parts of the world outside the U.S. for over 7 years and have substantially assisted the safe rule-in or rule-out of AMI. The U.S. has now approved and adopted the assays, with the first next generation troponin T test approved by the FDA in early 2017.

These tests are performed on state of the art central laboratory analyzers. However they are expensive and typically take, after assessment, transport and interpretation times at least an hour to turn around results – when minutes are vital.

To meet this need the market requires a device capable of conducting high sensitivity troponin tests at the Point of Care (“POC”); rapidly, cost effectively, and easily – taking high sensitivity laboratory quality testing to the patient in emergency settings for the first time.

MIDS – The New Way of Assay Detection

device

Immunoassay tests are commonly used to diagnose a whole host of diseases and medical conditions. In general many of these tests rely on the manipulation of paramagnetic assay beads. At the detection stage laboratory analyzers generally use optical technology to quantify these assay beads.

The analytical sensitivity gap between central laboratory testing platforms and existing POC testing devices is significant. The relatively bulky optical technology has not been successfully miniaturized into high sensitivity capable, hand-held devices.

MIDS takes an entirely different detection approach to the key element of assay bead detection. The ground breaking, patented MIDS technology can detect and measure commonly used assay beads by recognising, very accurately, their total aggregated nanomagnetic signal. This makes MIDS suitable to be incorporated into a miniaturized, cost effective hand held device.

Significant development work has been carried out with quantitative testing conducted to determine the minimum number of assay beads that can be detected and to prove linearity of detection signal to quantified bead numbers. MIDS Medical has been advised by Future Diagnostics Solutions B.V. (a leading assay developer engaged to MIDS Medical) that a capability to detect below 200,000 assay beads and preferably less than 110,000 is required to support a high sensitivity troponin test in the context of the proposed MIDS test strip.

Two brands of beads were tested: GE Sera-Mag™ (3μm) and Thermo Fisher Scientific M-270 Dynabeads® (2.8 μm), 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 these brands was seen on a reliable, repeatable basis at around 50,000 beads, with good signal linearity (required for accurate assay quantitation) at higher numbers. This number of beads detected at the limit of detection is approximately four times better than the maximum advised threshold and therefore well within the range advised by Future Diagnostics 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.

Market Opportunity

The global market for cardiac biomarker diagnostic tests is projected to reach $13.3 billion by 2024, of which only $1.16 billion is expected to be served this year by Point of Care devices. This market in its infancy; existing Point of Care hand held devices are not capable of performing true high sensitivity troponin testing. We are confident that our device and test strip, incorporating the breakthrough patented MIDS technology, will be capable of matching or exceeding the latest state of the art laboratory analyzers, and achieve unparalleled levels of accuracy, speed, reliability, ease of use and cost savings with the following key benefits:

  • Accuracy – Results that are superior or equal to high-sensitivity laboratory testing
  • Rapid Results – Single troponin I or T test aimed to produce a result within 3 minutes; three-panel test to identify additional cardiac biomarkers within 8 minutes
  • Cost Savings – Quality results not requiring interpretation by specialized medical personnel provided at a fraction of the cost of laboratory analyzers
  • Ease-of-Use – Designed for handheld testing and reading and ease in operation by minimally-trained personnel
  • Multiple Tests – MIDS is expected to be able to test most cardiac biomarkers (i.e., troponin T&I, D-dimer, myoglobin and CK-MB) at the magnetic nano-particle level
  • Patient Friendly – Testing will require only a small pin-prick blood sample, whereas existing AMI troponin tests require from 3 to 400 times this amount

If successful, Zenosense predicts that MIDS Cardiac will become the device of choice for hospitals, emergency rooms, family practitioners, paramedics and low resource settings, not only meeting a huge unmet medical need, but also positioned to achieve significant market share in the multi-billion dollar cardiac biomarker testing market.

The Future

While the initial focus is on cardiac testing, cardiac markers are just the first in a variety of potential uses for the MIDS technology platform. A successful MIDS Cardiac would demonstrate the value of the MIDS technology. The technology could then be applied to a wide range of POC immunoassay tests, to disrupt the market and provide a new level of accuracy, cost, ease of use and speed of POC testing across numerous immunoassay tests.

These tests include, but are not limited to, testing for conditions such as cancer, stroke, inflammatory / autoimmune disease, bacterial and viral infections and many more indications. These common medical tests are performed at an enormous expense through multiple daily assays in testing laboratories worldwide. MIDS technology has the potential to revolutionize this market that is growing at a rapid pace and projected to be worth $25.45 billion per year worldwide by 2021.

Question and Answer

Cardiac troponin is well documented as the preferred biomarker for diagnosis of myocardial infarction due to the high sensitivity and specificity for myocardial injury. Evidence continues to show that high sensitivity troponin is emerging as one of the most powerful prognostic biomarkers for the assessment of cardiovascular risk in the general population. Over the past 10 years cardiac troponins T and I (cTnT and cTnI) have emerged as the cardiac biomarkers of choice for the diagnosis of Acute Myocardial Infarction (AMI, heart attack).

High sensitivity troponin assays (hs-cTn) carried out on laboratory analyzers have been in clinical use in other many of the world for several years, including in Europe, Canada, and Australia. In early 2017 the US Food and Drug Administration (FDA) gave 510(k) clearance to the fifth-generation Roche Elecsys Troponin T STAT assay, which is the first high-sensitivity or “new generation” troponin assay approved for use in the United States, These high sensitivity tests achieve very high levels of accuracy but the process is slow, impacting the crucial turnaround time (TAT). These analyzers are also extremely expensive. Numerous alternative Point of Care devices are available. They are regularly used because of their fast TAT, no other viable option being available when time is so critical. However the analytical gap between high sensitivity laboratory analyzer tests and Point of Care assays for cardiac troponin is considerable. In reality there are no high sensitivity Point Of Care devices available for clinical practice in the “Golden Hour” which can compare with the growing use of high sensitivity central laboratory cTnT and cTnI assays.

Laboratory analyzers and Point of Care tests are generally carried out by manipulating tagged paramagnetic assay beads and using optical technology to detect them. Large central laboratory analyzers use state of the art 2D cameras during this process, have the capabilities to run multiple tests simultaneously, and embody other techniques to achieve high sensitivity results.

Point of Care devices, due to their considerably smaller size, cannot miniaturize the same technology. They are limited to optical detection of a lesser capability. In simple terms the assay beads are only viewed one or two dimensionally by the optical-sensing techniques. Only surface visible analytes are detectable.

In contrast the MIDS technology is capable of detecting extremely low levels magnetic field disturbance (nano-Tesla) caused by the test particles. This allows detection on a three dimensional level by detecting and measuring the magnetic signature of the aggregated assay beads using a lab-on-chip test strip. The MIDS technology has already demonstrated that it can detect suitably low numbers of commercially available assay beads used for high sensitivity troponin testing. This offers the prospect of developing a new Point of Care device with accuracy equal or superior to existing high sensitivity laboratory tests.

In summary, the MIDS technology should deliver orders of magnitude accuracy improvement in an inexpensive, easily operable device, in minutes from a small finger prick sample with rapid and unparalleled TAT. Effectively the Holy Grail of POC testing, MIDS for cardiac markers can accelerate diagnosis of suspected AMI at first medical contact, revolutionizing the triage, enabling early patient treatment and disposition, saving lives and dramatically reducing healthcare costs.

The MIDS technology platform (under license) is robustly protected by patent applications now in the national phase in key geographic areas and already granted in China and the U.S. (grants in other territories are expected to follow).

The technical challenges posed by the complexities of the detection method are a natural protection over and above the formal Intellectual Property protections. The MIDS technology is, as far as we are aware, unique; it is the first miniaturized technology to have demonstrated the magnetic detection of diagnostic assay beads in low numbers suitable for a high sensitivity troponin assay. The MIDS Medical approach, using miniaturized bespoke extremely high sensitivity Hall Effect sensors is a highly specialist area. The MIDS Medical team have unparalleled expertise in this field; with many years of high level experience in nano-magnetic measurement and Hall Effect sensor design and application, specifically in applications in the Point of Care field.