SCIENCE

Cancer deals a devastating one-two punch – every year – by claiming 8 million lives worldwide while cratering $2.5 trillion in economic impact. Over 40% of patients wipe out their entire life savings within two years of diagnosis. This is unsustainable.

Next generation cancer supermodels built on CerFlux ChipMux™ - including POET®, PEER®, POETRY, and PROPHET - can deliver a one-two counterpunch by enhancing our understanding of mechanisms of cancer and by deploying this knowledge to combat cancer at every stage: from protective measures to early diagnosis, optimal personalized therapy, and precision post treatment surveillance.

Each category – in vitro, in vivo, ex vivo, in silico – undergirding cancer models is in a state of renaissance resulting in a faster pace of new knowledge across the bench to bedside continuum.

Despite advances in therapeutics, cancer remains the second leading cause of death worldwide, and next-generation cancer models could help change that. However, obtaining enough tissue for ex vivo precision and personalized medicine can be challenging by tumor type and biopsy site. Current expansion approaches such as patient-derived xenografts (slow to establish) and patient-derived organoids (limited by size/scale), have practical constraints. Here we present 3D bioprinted organoid tumors (BOTs) that mimic core needle biopsy tissue, aiming to reduce time, cost, and barriers to evaluating novel therapeutics. We report producing and applying BOT core biopsy tissue for ex vivo testing, validating 3D microarchitecture with high-content fluorescence imaging and custom image analysis, measuring diffusion of stains and mock agents to 200 μm depth, and quantifying spatially distinct drug activity within intact BOT cores using advanced image-processing modules.

Nearly 70% of diagnostic lab test errors stem from variability in preanalytical factors—everything from when tissue is removed from the patient to when it is tested in the lab. Because preanalytical protocols are often not standardized, specimen integrity can be compromised. Establishing clear protocols would help remote collection sites reduce variability in specimen viability and integrity, improving test rigor and reproducibility and supporting innovation in live-tissue diagnostics for personalized medicine. Here we present findings from a study on how cold-chain logistics affect solid tumor specimens, evaluating transit time, container and wet-ice packing, and transport media composition. Overall, standardized preanalytics can strengthen diagnostic reliability and enhance the predictive value of next-generation cancer models for translational research and bedside applications.

Nearly half the world will be diagnosed with cancer, and more than 1.7 million new cases are diagnosed each year in the U.S. Worse, systemic therapy is ineffective in ~70% of patients because the drugs don’t match the patient’s tumor, creating major physical, emotional, and financial burden. Because tumors are heterogeneous, the same treatment can produce very different responses across patients, making personalized approaches - based on testing efficacy directly on a patient’s own tumor tissue - fundamentally better than today’s trial-and-error care.

Here we present findings from our low-cost, ex vivo personalized solid tumor biopsy-on-a-chip platform designed to rapidly evaluate multiple therapeutics on intact core biopsy tissue before treatment. Core biopsies were generated from xenograft and human tumor tissue using 18- and 20-gauge spring-loaded biopsy systems. We observed and quantified differential activity of anticancer agents versus mock drugs using custom image-processing algorithms.

Despite advances in high-throughput screening, combinatorial chemistry, databanks, and computational models, drug R&D remains expensive and slow—often taking over a decade. Pharma companies spend nearly $90B annually on preclinical research and trials, yet about 90% of drugs that look effective in pre-human studies fail in human trials. A key reason is that many preclinical efficacy methods don’t faithfully recapitulate in vivo microenvironments, driving failed trials and major time and cost burdens.

We developed a patented “Lab-on-a-Brane” (LOB) that better recreates in vivo tissue microenvironments, including barrier and transport functions, enabling organ–capillary interface models. We expanded the platform to support an air–liquid interface (e.g., lung microvasculature), then extended it to a “tumor-train” to model migration and invasion. Finally, we transformed the approach into a scalable, clinically relevant ex vivo Simple Microchamber Array Technology (SMART) that can concurrently assess multiple regimens directly on patient tissue.

This patent covers a human-relevant, ex vivo drug response screening and prediction method that uses viable patient-derived tumor tissue with intact extracellular matrix (ECM) to evaluate cancer therapeutic candidates outside the patient. The workflow emphasizes standardized collection and storage to preserve viability, preparation for analysis, and 3D microarchitecture and tumor microenvironment characterization of both ECM and cellular fractions to inform correlation and engineering of tissue proxies. Therapeutic candidates are then assessed by direct exposure on live or engineered tissue, enabling functional response evaluation in a setting designed to better reflect tumor biology than simplified models. Overall, the method supports a more rigorous, translational path for human-relevant NAMs based drug screening and personalized evaluation while retaining the complexity of intact tumor tissue.

With continued support from BCRFA, this project focuses on characterizing the controlled delivery of multiple isolated fluid streams to spatially distinct regions of intact breast cancer core biopsies within POET®. The work emphasizes rigorous validation of localized exposure, demonstrating that different agents can be applied to defined areas of the same biopsy while preserving native tissue architecture. By enabling spatially resolved, parallel testing within a single patient sample, the study strengthens the scientific basis for multiplexed efficacy assessment in ex vivo breast tumor tissue. This capability also supports more efficient use of limited biopsy material while generating richer, region-specific response data from each specimen.

Simple Microchamber Array Technology (SMART) is our patented biomimetic microchamber array device and set of methods for multiplexed exposure of intact biological samples to an array of fluids in parallel using microchannels and open-top microchambers. The architecture enables simultaneous evaluation of multiple compounds or conditions on a single intact tissue sample, supporting side-by-side comparison while preserving tissue microarchitecture. After exposure, samples can be characterized for response, viability, and related phenotypes to support comparative assessment across conditions. By compressing many test conditions into a single run, SMART is designed to increase throughput, conserve scarce patient material, and accelerate R&D iteration for human-relevant evaluation workflows.

This issued CerFlux patent builds on our Lab-on-a-Brane innovation to deliver a configurable, human-relevant way to model barrier and transport behavior under realistic flow. The invention uses modular cassettes, such as an engineered scaffold positioned between fluidic chambers, integrated into a closed-loop recirculating system where flow and pressure can be precisely tuned to approximate in vivo-like dynamics. Because the cassettes can be scaled and reconfigured, including multi-cassette arrangements, the platform supports a range of R&D workflows where interfaces matter, from transport and PK-style studies to head-to-head compound evaluation in physiologically meaningful conditions. This architecture is designed to help teams generate more decision-ready data by bringing controllable physiology into an experimental format that is practical to deploy and iterate.