61 The next generation of Precision Medicine – Bioelectronics The JournalMedicine of Precision An interview with Michael Heltzen and Brett Goldsmith MANY EFFORTS IN the past have been made Goldsmith of Cardea Bio to ask a few questions Bio-Layer Interferometry (BLI), next-generation to link biology directly to various read-out on the technology and applications of the device sequencing (NGS), etc.), many of which contain technologies to make molecular control signals directed to how this platform could be used to outdated methods and technology (e.g. sample accessible for monitoring in near-real time. advance precision medicine in drug development prep for optics) nearly a half-century old. Cardea Bio has taken up this challenge with a new and in the clinic. Optics-based technologies (SPR, BLI) class of devices that transduce biological binding contain an inherent limitation when it comes to surface events to a signal generated in a substrate. Q1. What are the benefits that Cardea Bio measurement; the molecules they aim to detect The key to Cardea’s approach is to stabilize brings to the market compared to are often smaller than the wavelengths of light receptor biomolecules on the gate of a graphene related measurement platforms in terms needed to observe them optically. As a result, for transistor that bridge biology binding events of e.g., sensitivity, selectivity, speed? example, technologies that measure nucleotides on the transistor’s surface to an electrical signal In this regard, how does Cardea Bio (e.g. NGS) require the mass-amplification of the in the transistor’s substrate. Cardea Bio’s mission differentiate its performance relative target molecule to meet the minimum threshold for is to provide a means to connect digital networks to competitive systems? detection. Additionally, optics-based technologies (the Internet, computers, and our cell phones) cannot directly detect amino acids; rather, they to the networks of biomolecular signals measure A. The Cardean Infrastructure has several distinct rely on secondary tags bound to the target to by the device. advantages over traditional measurement platforms produce a detectable signal, providing an indirect We contacted Michael Heltzen and Brett (lateral flow, surface plasmon resonance (SPR), approximation at best. Where optics-based Journal of Precision Medicine | Volume 7 | Issue 2 | June 2021 thejournalofprecisionmedicine.com @journprecmed Journal of Precision Medicine | Volume 7 | Issue 2 | June 2021 62 Figure 1: A diagram describing the action of the Cardean biology gated transistor. A capture chemistry such as an antibody is connected to the graphene surface. The graphene is constructed to be part of a liquid gated transistor. At the start, there is nothing bound to the capture chemistry. technologies provide a snapshot of a biological detect biomarkers in minutes, as well as binding learning algorithms that improve accuracy and interaction, electronic detection provide a near-real activity without amplification, including whole sample-to-answer times as well as letting us gain an time monitoring capability over the course of the genes, single nucleotide polymorphisms (SNPs), understanding of the biology. The current generation experiment. Finally, many traditional technologies and small molecules. of Cardea Infrastructure is already capable of require cumbersome equipment, complex We further potentiate the capabilities of direct unparalleled sensitivity, selectivity, and speed. protocols, and extensive training. electrical detection by using graphene at the core The Cardean Infrastructure overcomes of our transistor. Graphene is highly biocompatible, Q2. What portfolio of assays does limitations of optics-based technologies. unlike gold and silicon because it can operate Cardea Bio envision for precision Cardea’s direct detection does not rely on any directly in salt-solutions, such as biological fluids. medicine applications: tags that can interfere with the biomolecules It is also very sensitive to changes in its charge The JournalMedicine of Precision being studied, or cause non-specific interference environment such as those caused when two In drug development? that can influence results, as with optical molecules bind near the surface. When our target A. Cardean transistors are used by our partners technologies. Cardea is able to directly read and binds to the capture mechanism immobilized to the to do drug discovery via primary and secondary quantitate the biological signal in question in surface of our transistor, the binding event changes screenings, especially with respect to “hit to lead” near real time in live data streams. Our system the electrical properties of the graphene that can validation. This adds another fast, cost-effective, can detect molecules that are smaller than visible then be read as a robust signal (as diagrammed in platform that has demonstrated comparable rank wavelengths of light – allowing us to directly Figures 1 and 2). These signals are fed into machine ordering to BLI.1 Figure 2: A diagram describing the action of the Cardean biology gated transistor after exposure to the analyte. Binding to the capture chemistry causes a change in the overall transistor properties. Journal of Precision Medicine | Volume 7 | Issue 2 | June 2021 thejournalofprecisionmedicine.com @journprecmed Journal of Precision Medicine | Volume 7 | Issue 2 | June 2021 In clinical trials? rapid stratification of patients to the appropriate Q5. What are Cardea’s plans with A. Cardea’s platform could be used for a wide treatment. The opportunity with cancer treatments respect to FDA approval and marketing range of applications during clinical trials. is a great example of this. The use of liquid biopsy its products? Does Cardea Bio intend From real-time pharmaco-kinetics (PK), to techniques, such as with our InterCell-Chip to market an FDA-approved in vitro biomarker assays, to genetic screening for (for intercellular communication) or CRISPR- diagnostic kit, or will it go the laboratory- inclusion/exclusion criteria, and many more; each Chip sets (for gene or SNP mutations), presents developed test route? of these presents an opportunity for our partners an opportunity not only to diagnose cancer early, to provide a cutting-edge technology to support but also to assess which treatment would be A. Cardea works by enabling our Innovation clinical trials. most effective in the context of identified genetic Partners to utilize this technology to create mutations or abnormalities, active cellular destress disruptive products in their markets. This universe In the clinic? signals, or evidence of cancer cells hijacking of opportunities for Cardea runs the breadth of A. We see our technology as enabling in the field cellular components like exosomes to metastasize. markets, both regulated and unregulated. For our of rapid point of care (POC)/point of testing in The beauty of our system is its imminent ability partners in regulated markets, we help their ways not available previously. From enzymatic to combine several individual tests into one regulatory and commercial teams to devise an assays for newborn screening to infectious disease multi-omics chip. Instead of sending a sample to appropriate route, whether a cleared IVD kit or diagnostics to monitoring of immune responses sequencing, another for an immunoassay, and a a CLIA-waived LDT depending on the market after vaccination or immunotherapies, our partners third to enzymatic assay, our partners will be able and the application. Cardea then relies on its have the ability to provide a transformational to build products that combine it all on a single partners to market and distribute their “Powered way to understand patient health in prognostic, disposable chip. Thus, a physician will get a more by Cardea” product. diagnostic, or monitoring scenarios. complete and near instant picture of a patient’s 63 condition and can use those actionable insights Q6. What are Cardea Bio’s plans for In the R&D lab? to improve patient outcome. regulatory compliance in the US, the UK, A. R&D labs instruments and “quality control” the EU, and elsewhere? Does Cardea Bio applications like www.CRISPRqc.com are have a roadmap and strategy along the fastest moving markets we see in regard ‘Linking up to Life’ these lines? to deploying our technology via product Cardea is on a long-term mission, “Linking up A. development. This path offers a combination of to Life,” to empower its “Powered by Cardea” As a manufacturer of biosensors that will no or low regulatory hurdles and a strong market partners with Tech+Bio solutions that will enable be integrated into a wide variety of products, demand to solve a number of costly problems and impact via innovative applications. we intend to seek ISO 9001 and ISO 13485 bottlenecks identified and well understood by our For more information about Cardea Bio Inc. certifications. We believe this will be a critical “Powered by Cardea” partners. visit www.cardeabio.com path for us to support our partners in regulated markets, and we are a firm believer in providing Q3. Does Cardea Bio plan to develop safe and effective products for our partners companion diagnostics application for, say, Q4. In follow up to Q2 and Q3, and their consumers. Each product we design The JournalMedicine of Precision an assessment of a patient in a doctor’s what sample types does the Cardea with our Innovation Partners would require an office for a therapy? platform support – blood, sputum, individualized regulatory strategy determined by urine? What types of sample our Partner’s commercial goals and intended use A. Companion diagnostics represent a great place preparation are needed for in-office market. We work with our Partners to identify the for our future partners to utilize our technology for of in-laboratory applications? most effect roadmap for each product to create a win-win partnership that delivers safe and effective A. Being an all-electric system that does not products quickly to consumers. rely on optics, the platform can function in any biological fluid sample. The sample preparation Q7.