Biology is made up of a multitude of highly complex systems within systems that working together determine our reality; our health, our diet, and our physical traits, but also other aspects we may not think about such as cosmetic products, the health of our pets, or even societal issues such as the ability of society to manage substance abuse. And yet the more we learn about biology, the more it becomes apparent just how little we truly understand. Life science has been segregated into several different fields to simplify and understand it; genomics and proteomics and cell biology and virology are all distinct fields even though nature sees these as layers of interlocking, constantly communicating networks.

When we started Cardea, we noticed that the commercial attempts and the literature around graphene-based biosensors emphasized the “sensor” and underappreciated the “bio”. Most just put down some antibodies or DNA, measured in de-ionized water and imposed requirements in the measurement protocol that would be unrealistic in any deployable or laboratory application. They simplified the biology so much that it lost all relevance to nature.

Cardea has taken the opposite approach, focusing on the complexity of biology and making our design respect it.

Our patented Biology-gated Transistor, or Cardean Transistor™, design utilizes real-time liquid gating and works in full strength buffers. This makes for an extraordinarily difficult transistor to manufacture and the data is an analytical challenge, but its strength is that it allows for much simpler bioassays. We allow the biochemistry to work the way it works in nature, providing for a much more relevant response. Over tens of thousands of experiments, we have worked to understand the effects of complex media, different samples types and many other aspects so that the sensor mimics how the targets are found in nature. Today Cardea has more biologists then physicists or chip manufacturers because that relevance is critical to successful biosensing and has led us to adapt our technology to the reality of biology to bring real utility.

BIOLOGY ADDS FEATURES

In 2019, the entity that was Nanomedical Diagnostics merged with another startup, Nanosens, and in so doing became Cardea. We talk about Cardea having 4 co-founders, Brett and myself as well as Michael Heltzen and Dr. Kiana Aran who co-founded Nanosens. The two companies had a shared vision of merging the digital and biological domains, but Nanosens utilizedCardean Transistors to perform some truly outstanding biochemical breakthroughs we had never thought of. The respect for the biology that we brought from the beginning enabled the creation of CRISPR-Chip.

CRISPR-Chip is a derivation of Cardean Transistors that has profound implications. CRISPR is a complex of proteins and RNA that serves as the immune system of some bacteria. It fights viruses by sifting through any nucleic acids it finds and destroying targeted sequences. Scientists have appropriated and repurposed CRISPR for gene editing techniques, but Kiana was the first to realize that its search features were what made it special. By putting the CRISPR complex on the surface of the chip, the combined system can now be programmed to search for specific sequences, sift through an entire genome in just a few minutes, and if the target sequence is found, the chip responds right away. It can do this without amplification and function with nucleic acids in the natural state they are found, unlike PCR. CRISPR-Chip leverages the Cardean Transistor features and CRISPR’s unique searching capability to make an electronic DNA search engine, something never imagined before.

Our chip is not just a genomics or proteomics solution; it is a multi-omics solution. Because we’ve committed to working with biology with as little sample processing as possible, we can use the same chip and reagents to sense nucleic acids, proteins, and other types of biochemistry by functionalizing different transistors with different biology before the measurement. This concept is not unusual to the nanotechnology community, but for a life scientist, this is a major development. No bio lab instrumentation can look at all types of biology at the same time.

The first article in this series focused on how we put manufacturing first. Too often nanotechnologists fail to deliver the core product before they start trying to deliver easy to engineer features like wireless communication. When you combine a manufactured graphene chip and multi-omics with the tremendous benefits of electronic systems, such as low-cost manufacturing, portability, and wireless communication, opportunities never before possible have begun to open with our commercial partners. By mid-2020 Cardea has had over 200 companies sign up to the Cardea Innovation Partnership Program, where they have been proposing implementations of the Cardea Tech+Bio Infrastructure into their either existing product(s) or new product(s) for existing and new markets. This will result in first tens of, and later hundreds of, “Powered by Cardea” products hitting the markets over the coming years.

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CARDEA AND THE “TECH+BIO” VISION (Part I)

CARDEA: SCIENCE TO PRODUCTS (Part II)

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