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MiDiagnostics Developing 10-Minute Complete Blood Count Test, Multifunction Platform

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NEW YORK (360Dx) – MiDiagnostics is developing a silicon chip testing platform for use at the point of care that employs diverse diagnostic testing functionalities to detect cells, proteins, nucleic acids, enzymes, and small molecules. If it's successful, the diagnostic platform could be deployed for use in detecting an exceptionally broad range of medical conditions, company officials said.

The firm has plans to eventually develop on-chip detection for indications ranging from infectious diseases to routine conditions, but its first diagnostic assay would enable doing a complete blood cell count within 10 minutes, Leander Van Neste, the firm's vice president of scientific and clinical affairs, said in an interview.

The firm is developing the platform in collaboration with the Johns Hopkins University and Imec, an international R&D and innovation group that specializes in nanoelectronics and digital technologies. Their objective is to use silicon micromachining to create a platform and disposable test cards that provide the quality and accuracy of lab-based tests where they are most needed and where point-of-care testing makes the most sense, Van Neste said.

In the early 2000s, Imec began looking at opportunities outside of traditional electronic chip R&D and decided to explore life science applications. For medical advice and expertise, the organization reached out to Johns Hopkins University as a collaborator. In 2015, the partners decided that their combined work could expand beyond research into clinical diagnostic applications through the design of capillary nanofluidics on silicon chips for use in diagnostic applications, Van Neste said.

In 2016, Leuven, Belgium-based MiDiagnostics and its collaborators began to focus on applications where miniaturization of lab-based analysis could address unmet clinical needs, and the type of technology that needed to be implemented to make that feasible, he said. 

The exercise led to the firm identifying four diagnostics pathways using micro and nanofluidics — one based on imaging; a second based on PCR and nucleic acid detection; a third based on protein detection using fluorescence; and a fourth based on the detection of enzymes and small molecules. "The idea is that with these diagnostic pathways, we could use our lab-on-a-chip platform to do most of the routine testing done in the lab, because the vast majority of the testing is done using those four technologies," Van Neste said.

Andreas Weimann, managing director of Labor Berlin, a large hospital laboratory, and a member of the MiDiagnostics scientific advisory board, said that as a hematology specialist, he is "hooked by the idea of having a point-of-care device for complete blood counting."

"CBC analyzers are superb devices, but they always need experienced staff to run them," he said. "The way MiDiagnostics is doing this is intriguing. They have selected a platform, and you can connect all sorts of different tests if that platform works. Having an optical reader in a flow cytometric manner for CBC detection, for example, is really interesting."

Taint of Theranos

MiDiagnostics' platform development work comes against the backdrop of Theranos, which touted a platform that could detect a host of different conditions with one finger prick of blood. After running into trouble with regulators and news reports that its tests provided inaccurate results, the company said recently in an email to its shareholders that it was winding down.

Van Neste said that while Theranos' story has "tainted" a "whole sector … I believe the biggest difference is that we put the scientific facts above everything else.

"We do not promise that based on a single drop of blood we’ll be able to perform an entire battery of tests," he added. "We make clear choices to first develop the CBC and then gradually expand the platform with other targets. We know that this takes time and for us quality (results and processes) and regulatory [approval] are two topics we’re not willing to compromise on."  

Among the keys to the success of the platform is its underlying artificial intelligence technology and the algorithms behind it; the ability to do cloud computing; and the capability to extract all the relevant information from the data provided by the platform, Weimann said.

All four diagnostic pathways are enabled by silicon micromachining, which allows precise control of features at the micron level and is an important component of the firm's disposable test cards. In 2016, the firm and its collaborators conducted an analysis to decide which pathway was most suitable in developing a product in the nearest term, and they decided to move forward with a complete blood count with 3-part differential based on use of imaging for measurement and analysis.

Traditionally, clinicians perform CBCs as the first test during a patient’s checkup to evaluate their overall health. By measuring the number of molecules such as red blood cells, white blood cells, and platelets, the assay detects a wide range of disorders, including anemia, infections, and leukemia.

However, many clinics do not carry standard CBC machines due to their costs — usually around $10,000 to $20,000 — as well as the need for a trained medical expert to perform the assay. 

For this indication, MiDiagnostics envisions deploying its test in doctor's offices or for use in the home. If they are successful, patients would be able to conveniently use tests of complete blood counts to determine whether they have a bacterial or viral infection and whether their physicians should accordingly prescribe antibiotics or another drug.

Similarly, patients who are on chemotherapies could use the test to determine in collaboration with their physicians whether their blood counts are at a level where it's safe to undertake the therapy.

"Overall, we are looking at applications in CBC testing where labs are not able to achieve the best possible care because of a delay associated with getting a test result," Van Neste said. "We are targeting applications where we can add value, such as settings where testing needs to be easy to use and doesn't require much knowledge to take a test and get a result."

To achieve complete blood counting, the firm is developing autonomous, capillary fluidics that operate without pumps or actuators. It is also implementing computer vision and computational microscopy, which removes the requirement for complex and expensive lenses. The user inserts a sample into a test cartridge and the test cartridge into a reader that contains components that are easy to reuse, such as a light source.

The researchers are using holographic lens-free imaging technology developed by Imec. When the system shines coherent light on blood it produces a diffraction pattern from the different cells on an image sensor. "We are creating holograms of blood cells that we can reconstruct into a regular image and then count and identify the types of blood cells," Van Neste said. "The main advantage of this is that it is extremely compact," he said. "You need only a light source, and an image sensor. There are no lenses or moving parts, so it is more cost effective and compact to implement than to most alternative systems."

Johns Hopkins researchers developed lens-free image processing techniques for the complete blood count diagnostic test that improve the image quality of the holograms and allow a more accurate analysis by separating blood cells from the image background. They described their methods in the 2017 IEEE 14th International Symposium on Biomedical Imaging

Timeline

MiDiagnostics, which has raised €60 million ($71 million) since its founding, is conducting late-stage feasibility evaluations of the platform for use in CBC testing. The firm is now focusing on integrating the chip into a plastic cartridge for cost effectiveness and to enable manufacturing of an affordable point-of-care platform, and it expects to enter product development next year.

"We are starting preliminary experiments with sub parts of the system, but it will probably be 2020 when we start doing clinical validation with patient samples for the complete, integrated system, and 2021 when we complete the final clinical validation," Van Neste said.

The firm anticipates seeking CE marking and US Food and Drug Administration clearance, but it hasn't decided which one it will pursue first.

Other companies pursuing development of microfluidic complete blood count tests include PixCell Medical Technologies, which aims to introduce a test on the European clinical market by early next year, followed by a launch in the US, leveraging a €2.5 million ($3 million) grant to fund its activities.

Startup Essenlix also aims to address the costs and challenges of CBC assays in the clinical space with its cartridge-based smartphone-based instant mobile self-test technology.

According to Weimann, there are still questions related to the development of MiDiagnostics' platform, including those related to manufacturing processes, platform and assay validation, whether a finger prick of blood is the correct sampling method, and whether to place the system in homes or in hospitals, or both. For home-based applications, for example, users would need to have a robust connection to the cloud to ensure that results are generated in the desired timeframe.

With that said, the MiDiagnostics concept "is how a point-of-care platform should behave," he said. "This platform is open to PCR, clinical chemistry, immunochemistry, and to optical systems soon solving the challenge associated with having CBC differential at the point of care. No one else has a platform able to address all these different topics."