CytoAurora
Breaking New Ground In CTC Technology

Known for its ability to enhance cancer treatments profoundly, the circulating tumour cell (CTC) technology directly captures free-moving tumour cells in peripheral blood to help diagnose early-stage cancers. However, the lack of a breakthrough in CTC technology for over a decade is concerning. As such, the results produced by the CTC technology were no longer deemed accurate or feasible for clinical medicine.

For example, over the past few years in Taiwan, physicians have become increasingly reluctant to recommend CTC diagnostics to patients due to a lack of reproducibility and convincing validation. Rather, they opted for cell-free tumor DNA testing. Given CTC’s current shortcomings, it is essential to create better technology and build enhanced-performance equipment that can gain the acceptance and trust of physicians and patients. Fulfilling this need for innovation, the CTC technology offered by CytoAurora—a biotechnology firm—successfully integrates semiconductor,

microfluidics, molecular biology, AI, and automation/ robotics to create an accurate, high-throughput, robust, and automated CTC capturing system. “CytoAurora Biotech focuses on the technology called liquid biopsy, using a non-invasive approach to access the tumor hidden deep inside the human body,” says Dr. Chung- Er Huang (CE), CEO and founder of CytoAurora Inc. In addition, the company possesses strong technical background, with most members boasting more than 15 years of experience in their respective fields.

A special mention here goes out to a significant cornerstone of this team and an honorary consultant to the board since 2016, the world-famous clinician and geneticist, Prof. Ming Chen, MD, PhD, without whom none of CytoAurora’s technologies would come to fruition. Based in Taiwan, Prof. Chen graduated with medical and scientific degrees from the National Taiwan University (the most prestigious university in Taiwan) and the University of Glasgow (one of the most prestigious institutions in the UK).

The Core Technologies

Already with patents granted in Taiwan, China, and the US, along with seminal publications in prestigious medical science journals, CytoAurora’s core technologies can be categorized into three stages - cell capture, cell identification, and single-cell isolation. The company’s chips are made from semiconductor wafers with a process involving surface modifications, micro-fluidic etching, chemical vapour deposition (CVD), and detailed cutting. The CTC process begins when the peripheral blood mononuclear cell (PBMC) in the blood passes through the semiconductor micro-fluidic chip; the surface-modified chip captures antibodies on cell surfaces. Then CytoAurora uses an antibody to combine with specific antigens on the tumour cell surface to identify true cancerous cells. “Since different types of cancerous cells match with different antibodies, this method allows us to determine the type of the cancerous cell, the stage the tumor cell is at, and whether the tumor is malignant,” says Dr. Huang. In addition, CytoAurora’s self-developed and proprietary Cell Reveal System with high sensitivity capture rate for rare cells in the blood (including cancer cells and fetal cells) has significantly enhanced the CTC capture results. The system also features a semiconductor surface modification testing biochip accompanied by an in-house developed AI diagnostic analysis software Cell Analysis Tool (CAT) to quickly and accurately analyze data.

After capturing the cell and marking it with a specific antibody, CytoAurora puts the chip under a fluorescent microscope to identify the cell. Next, the company takes clinical samples to analyze, among many factors, the ratio of the nucleus to the cytoplasm and the size and integrity of the nucleus, and more.

Applying machine learning functions, the company’s AI ID software performs cell identification within five minutes. Next, for single-cell isolation, CytoAurora places nanometer-level scaled coordinates on its self-made semiconductor chips. “When we need specific cells from our chip to perform genetic analysis or cell culture, we place the chip on another piece of equipment, the ‘Cell Picker,’ also made by us. All of this is easily accomplished thanks to our strength in integrating nano-semiconductor and precision-machinery technologies,” says Dr. Huang.

Cases on Point

CytoAurora’s CTC system can be applied toward early cancer detection, cancer treatment, and remission monitoring; the system can also provide physicians with medication prescribing guidance. The company has worked with a hospital in Kaohsiung on a clinical research project focusing on treatment and remission monitoring of liver cancer patients. The company assisted physicians in analyzing the effects of the treatment to understand if the treatment method should be improved or revised. CytoAurora’s CTC was employed to determine cancer cells’ number, characteristics, and conditions inside the patient’s body, thereby enabling physicians to select the proper treatment method. “This engagement proved that we can provide physicians with the correct information to allow them to assess if the treatment method is effective right away,” says Dr. Huang.

In other cases, doctors used CytoAurora Biotech’s CTC system to screen out particular antigens found on the cancerous cell surface inside the patient’s body to determine the type of targeted therapy or immunotherapy to use as a treatment for patients. After monitoring these treatments for six months, patients’ tumors were found to be in full regression, which again showed that CytoAurora’s CTC system was able to help doctors in making the proper judgment on the treatment strategy. In addition, there are other clinical cases where abnormal cancerous cells were detected by CTC in subjects’ blood specimens. Medical imaging, like a low-dose CT scan, would then be carried out on these subjects to confirm abnormal images of tumours, thereby allowing for early detections of cancer as well as early treatments. “These cases are part of an ongoing clinical research project which we’re working on with a participating hospital. We plan to publish the results of this research in journals by the second half of this year,” says Dr. CH Tang, the Vice General Manager who is responsible for sales, marketing, and product developments.

The Rich Resources

Since CytoAurora’s R&D facility is based in the world-renowned Hsinchu Science Park in Taiwan, it can benefit from the advantages offered by the country. The first advantage is Taiwan’s mature semiconductor industry, which has an output value that is the second-largest globally.In addition, the country boasts the best medical care in Asia; many polls and surveys have ranked Taiwan among the top 3 in the world in terms of the medical care system and service quality.

Third, the output value of Taiwan’s precision machinery industry ranks 5th in the world. Finally, the country offers outstanding biotech experts and engineers. All of these advantages help contribute to CytoAurora’s innovation in CTC technology. More importantly, due to the perfect synthesis of semiconductors, AI, precision machinery, and molecular biological technologies, CytoAurora’s self-developed proprietary Cell Reveal System has significantly enhanced the CTC capture results with higher sensitivity and accuracy.

Even though CytoAurora Biotech is a new start-up, its team consists of experienced veterans from various disciplines who bring their own skill sets to the development of science and medicine. “Our CTC diagnostic technology is fast and accurate thanks to the successful integration of semiconductor, bio, medical, and AI technologies. This is a unique strength that none of our competitors possess,” says Dr. Huang.

This differentiating key feature enables CytoAurora to break through all the barriers to entry in a short span and successfully and systematically integrate various clinical development disciplines to produce innovative products and services. The company proudly claims that every piece of equipment it has produced and the technology and patents behind it are completed owned by CytoAurora. In addition, “we have our certified lab and a good-manufacturing-practice factory. The combination of these allows us to surpass our competitors in terms of development speed, flexibility toward market needs, and cost control,” says Dr. Huang. While it has only been six years since its inception in 2015, the company has already collected nearly 20 patents and is still fast accumulating more.

“All of CytoAurora’s equipment has been designed, developed, and manufactured by ourselves, which is something that none of our competitors can say. Because of this advantage, the company can quickly design and manufacture equipment and products like the Cell Picker according to the needs of the end-users,” adds Dr. Huang.

The founder and CEO’s words also shed light on industry reports and statistics that suggest tumour detection with blood or other liquid samples is becoming extremely important in the global market year by year. To that end, CytoAurora focuses on enhancing the technology of liquid biopsy in cancer research and management. Alongside, the company is set to roll out new products and services in the medical field every year. “We plan to provide newly developed equipment and technical support, build production bases in mature markets, and provide sales, marketing, and clinical services with local partners. With this working model, we hope to connect with the world and enter the international arena,” adds Dr. Huang.