Organoids have transformed preclinical research, offering human-relevant models that reflect tissue-level complexity better than traditional cell cultures. Yet many assays that assess these 3D structures still rely on indirect molecular or morphological readouts. Building on more than a decade of experience in high-density in vivo neural recording, Diagnostic Biochips developed SomaFocus to measure live electrophysiological activity directly within 3D neural cultures. The automated system inserts ultra-fine silicon probes into intact organoids, generating in-depth data on coordinated neuronal firing and network dynamics.
Brian Jamieson, PhD
Chief Executive Officer and Founder
Diagnostic Biochips
In this Innovation Spotlight, Brian Jamieson, the chief executive officer and founder of Diagnostic Biochips, discusses how the company’s innovation is bringing functional biology into disease modeling, neurotoxicity testing, and therapeutic discovery.
What are the main challenges in translating preclinical screening assays into clinical outcomes?
The drug discovery and development process is lengthy, expensive, and risky. Issues with the potential to kill a promising therapy can arise at every step, from early lead development to late-stage clinical trials. Diagnostic Biochips is focused on improving the predictive validity of preclinical assays. In simple terms, this means that we seek to improve the ability of early-stage or preclinical assays to determine which candidates are most likely to be both safe and efficacious in patients, thereby reducing late-stage failures driven by misleading early signals.
How can organoids bridge this gap, and what hurdles remain despite this technology?
Organoids are complex human cell-culture-based models of systemic function at the organ or tissue level. Because they are genetically programmable, they represent an unprecedented opportunity to develop realistic models of complex systems, such as the brain, for studying drug efficacy and safety. However, challenges remain, including variability between organoids, maturation state, and the need for better functional readouts to interpret complex behavior.
What inspired the development of your instrument, and how does it work?
We were inspired by the mismatch between how 3D organoids are currently interrogated and the tools we had already developed for recording cellular activity in real 3D neural networks in living brains. Our instrument works by automatically inserting an extremely fine silicon sensor, essentially a needle with dozens of cell-scale recording sites, to measure cellular activity without disturbing the underlying cellular structure.
What types of organoids can SomaFocus assay?
While our primary focus is on brain organoids, spheroids, and assembloids, we are also carrying out important work with customers studying intestinal, retinal, and skin organoids. All these systems contain electrically active cells that carry out important functions in normal and pathological contexts and are useful models for drug discovery.
What insights can scientists gain from their 3D models using SomaFocus, and why are direct functional readouts so important?
To give a specific example focusing on brain organoids, nervous system function depends on the coordinated and sequenced firing of large groups of individual neurons. With SomaFocus, we can eavesdrop on those neuronal firing patterns and apply cutting-edge software trained on decades of real brain data to analyze those sequences and gain information about both normal and pathological activity. Seizure activity in models of epilepsy or focal hyperactivity in Alzheimer’s disease are two examples. These functional patterns are often invisible to purely structural or molecular assays, yet they are among the most clinically relevant signals. By dosing organoids with candidate therapeutics, we can determine whether network function becomes less pathological.
What role does automation play in screening with SomaFocus?
When you consider the sheer volume of compounds that must be tested and the need for statistical power, automation is table stakes—a basic necessity. We have developed a system that does not require user intervention beyond sample loading, and we increasingly apply machine learning to characterize and analyze the data at high throughput, making the platform suitable for real-world drug discovery pipelines.
What excites you the most about this technology?
As a group of entrepreneurial scientists, it has been incredibly exciting to discover that a solution we developed in a different context—high-density neuronal recording in vivo—has become an enabling solution in a totally different context: in vitro models. It is a real thrill to watch SomaFocus users light up when they see the data coming out of these models immediately upon insertion and to watch the exponential growth occurring in this field.
Is there anything else you’d like our readers to know?
We believe functional biology is the missing layer in organoid-based discovery. Structural and molecular data are essential, but without direct functional readouts, it is difficult to predict clinical outcomes. Our goal is to help establish functional phenotyping as a standard component of preclinical screening, accelerating the translation of promising therapies into the clinic.
