Abstract LB-285: Rapid needle biopsy assessment at point of care to advance personalized cancer therapy
Authors: Cooper David J. , Fauver Mark E. , Dintzis Suzanne M. , Seibel Eric J. 
Published: September 2020

Abstract
Rationale: Although core needle biopsies (CNBs) are the preferred minimally invasive procedure for breast cancer diagnostics, the standard of care H&E histopathologic analysis of core biopsies is both tissue destructive and labor intensive. Our novel millifluidic instrument, CoreView, is designed to evaluate fresh CNBs to make a real time cancer diagnosis or adequacy determination, conserve tissue for downstream diagnostics and assist in timely treatment planning. Technology and Methods: CoreView is designed to handle, stain, and transport CNBs with the use of millifluidics. The first stage of the CoreView removes biopsy procured tissue from side-cut and end-cut needle-type biopsy guns (14-16 gauge). The reliability of the novel low pressure fluidic process in removing intact CNBs was tested using freshly-excised (ex-vivo) porcine breast (N = 28), kidney (N = 21), liver (N = 42), lung (N = 25), and lymph node (N = 30) tissue. The shear rate, provided by the driving pressure of saline solution, was increased in increments until the CNB was removed and the resulting intactness was qualitatively analyzed by preserved overall shape and size. For optical imaging, a second stage streams fluorescence dye over the CNB for H&E equivalent staining. High resolution imaging with 285 nm excitation is currently performed using microscopy with UV-surface excitation [MUSE, Levenson Group, UC Davis] for anatomical imaging. Previous studies have shown the optical sectioning thickness of MUSE is about 3x thicker than microtome-sectioned specimens. To improve the quality of images produced by MUSE within CoreView, we are limiting UV tissue penetration by steric hindrance of dye molecules using conjugated nanoparticles, such as 525-705 nm CdSe Qdots [ThermoFisher], as well as optical blocking dyes as counterstains. Results: The CNB removal stage was 3D-printed in a patent pending disposable design which is optically clear for monitoring the process. CNBs were fully released and structurally intact for analysis in 93% breast, 100% kidney, 100% liver, 84% lung, and 90% lymph node CNB samples. The average volume per time (µL/ms), an analog to shear rate, for each tissue type was 2.19 (σ;; = 1.04), 1.97 (σ;; =0.71), 1.74 (σ;; = 0.87), 2.05 (σ;; = 0.87), and 2.01 (σ;; = 0.87) for breast, kidney, liver, lung, and lymph node, respectively. The CNB tissue was removed in under 15 seconds, some as quickly as 2 seconds. Furthermore, the device's round channel, which holds a CNB with diameter 10-20% less than the channel, results in inherent structural preservation. Conclusions: The novel millifluidic biopsy removal device is an essential first stage to CoreView's automated biopsy handling and future MUSE imaging and adequacy analysis. The customizable CoreView system design allows optimization for specific CNB needle, tissue, and imaging procedure. We predict an adequacy check at nearly 100% reliability in CNB release and integrity within a few minutes at the point of care.
Citation Format: David J. Cooper, Mark E. Fauver, Suzanne M. Dintzis, Eric J. Seibel. Rapid needle biopsy assessment at point of care to advance personalized cancer therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-285.