Dr. Jonathan Hull, Co-Founder and Vice President and Roger Chen, Founder and President
Great innovators often think laterally! When exploring new ways to address an age-old problem, an inventive mind always thinks ‘outside the box’ to find an unconventional but effective solution. By doing so, they create a wider spectrum of possibilities. Such thinking and quick iteration can produce astonishing results in a relatively short time. The field of cell biology witnessed similar innovation when Roger Chen, the president of Bioelectronica, came up with new, revolutionary tools for protein and cell-based assays.
Earlier, if one were to propose the possible applications of planar processing—which have strictly been associated with technology in the semiconductor industry—in cell biology, they would be met with scepticism and raised eyebrows. However, Chen did not just put forward the use of planar processing as a reliable way to bypass the scalability issues of traditional protein and cell assay techniques; he made it a reality with his company. Bioelectronica is a research-stage biotechnology company building next-generation digital tools for drug discovery, diagnostics, and cell sorting at a nanoscale level. Chen states, “I have always felt that a key part of technology is decentralizing advanced technologies.”
Breakthrough at the Cross-Section of Electronics and Chemistry
As an engineering application sales support executive in an integrated circuit (IC) manufacturing company, Chen witnessed the role of planar processing in the evolution of electronics during the 90s. Planar processing has been the catalyst behind the miniaturization of computers and the pervasion of today’s high-performance smartphones. This experience led Chen to leverage the same concept to offer substantial disruptive cost and scaling benefits to biochemists. After successfully using electronics to measure single molecules of DNA in a sequencing system, Chen built a compact and high throughput next-genDNA sequencer at his first biotech start-up. However, this was still not Chen’s vision; even though he was able to reduce the size of the device, the operation remained lengthy and cumbersome. The core idea is to get rid of the complicated robotic arms. Determined, Chen went further on to use sleek, scalable, low-cost tools to mitigate the need for robots and fluorescence-based analysis in biochemistry research.
"By uniquely coalescing chemistry and engineering, we have developed an alternative to analytical tools like fluorescence-activated cell sorting along with an alternative to liquid handling robots and other traditional methods"
The result was his next venture, Bioelectronica, where he developed “electrofluidic chips”—flexible electrode materials that are normally used in phones but have been modified to allow fluids with biological materials to flow through them. These chips are built using planar processes to solve a core problem in biochemistry and cell biology: building scalable infrastructure for manipulating small (nanoliter) volume of liquids and detecting important biochemical events that are used in biochemical research.
I have always felt that a key part of technology is decentralizing advanced technologies
The availability of electrofluidics is a massive advance for cell biologists and drug developers because the technology easily scalable to billions of reactions (due to planar processing).This means that the transport and sort single cells based on their secretion rate and other properties can be scaled to mind-boggling schemes of billions of biochemical events and chemical reactions running in parallel.
Such prowess of Bioelectronica is rooted in the amalgamation of Chen’s background in engineering and the company’s co-founder and vice president Dr. Jonathan Hull’s experience in chemistry. Their combined expertise made Bioelectronica the only company that can use computer vision to calculate the concentration of molecules or proteins so that detection can be scaled with fluid flow. “By uniquely coalescing chemistry and engineering, we have developed an alternative to analytical tools like fluorescence-activated cell sorting along with an alternative to liquid handling robots and other traditional methods,” comments Hull.
Bioelectronica’s Road to Success: Unity in Diversity
At a time when the critical oversight of many companies is the integration and management of different technical expertise, Bioelectronica’s success stems from successfully blending diverse sets of skills and knowledge of its employees. Its team includes experienced molecular biologists and software engineers working in horizontal collaboration. The engineers, well versed in the electronic supply chain, suggest the reagents that their devices are able to detect. Based on this, the molecular biologists develop specific reagents for molecular signalling that include enzyme-linked immunosorbent assay (ELISA), signalling clusters, and many others. These signalling processes, coupled with electronic supply chains, offer a unique way of observing molecular signals with naked eye, allowing computer vision to be used as an analytical chemistry method. This allows analytical chemistry to become into new engineering platforms with endless possibilities. For example, Bioelectronica has developed novel reagents and software comprising an Enzyme-Linked Darkening Assay (ELDA™). The new assay system is being validated for the detection of several inflammatory markers.
A Novel Way of Sorting Primary B Cells
Soon after ELDA™, the Bioelectronica team discovered that they could rapidly detect secreted antibodies from cells with thesame computer vision system. By using “flex” electronics, the company developed “electrofluidic” chips that can also sort the cells based on rate of antibody secretion. This has appeal to drug companies developing monoclonal antibodies. The traditional Hybridoma based technology is time-consuming and expensive.
A common approach is Hybridoma technology, which overcomes the short life span of IgG-secreting plasma B cells in vitro. However, many plasma B cells are lost due to the low efficiency of hybridoma cell fusion (typically <10%).
Notably, Bioelectronica enables biochemists and drug discovery companies to directly sort and recover B cells by their antibody secretion rate in timeframes of hours and days instead of weeks and months. Rapid screening of this sort has not been feasible using traditional methods until very recently, and Bioelectronica is the “New Kid on the Block.” Instead of working with hybridoma cells (which contain plasma B cells) the company prepares nanoliter volumes containing single B cells by encapsulating them in its homegrown emulsion-based matrix known as PODs (Polydisperse Oblate Dispersion System). Users can then load the encapsulated B cells into parallel flow channels embedded with imagers, and they can identify antibodies that are being secreted by each cell by detecting bead-based reagents that respond to antibody secretion using a proprietary computer vision technology.
"There are a number of applications in the pipeline. We have had requests ranging from antibody discovery, to quality control to CAR-T applications"
Considering that isolating high-antibody secreting B cells are a key bottleneck for the drug discovery market, collecting the desired B cells is crucial to developing and maintaining a robust immunotherapy pipeline. Chen quips, “It is like searching for a needle in the haystack.” This is where Bioelectronica employs its proprietary electrofluidic chips. This approach of B cell sorting has especially proved beneficial for pharmaceutical companies and CDMOs as they can cut down on both the timeline and cost of general cell sorting techniques. The company is working globally with big and small pharma companies alike because of the broad appeal and ease of implementation.
The Beginning of a New Era
Beyond developing an effective alternative solution for existing assays and workflows, Bioelectronica is also developing newer assays that leverage cell-surface display markers, and cell death in combination with secreted antibodies. These new assay techniques will enable pharmaceutical companies to develop custom assays that are not available at present. “There are a number of applications in the pipeline. We have had requests ranging from antibody discovery, to quality control to CAR-T applications. The beauty of this platform is the adaptability to new applications and rapid iteration on chip design. Our rapid build-test cycles are much faster than others in our field and will give our customers a step-change in innovation.”
Bioelectronica is truly bringing drug discovery into the next century; tools like real-time computer vision, artificial intelligence, and systems integration are often talked about among venture capitalists and pharmaceutical companies, but are rarely found in reality. In this regard, the company is leading the next generation of tools for biochemists and transforming the methodologies used in drug development.