Beyond isolated cells: microfluidic transport of large tissue for pancreatic cancer diagnosis

Abstract

For cancer diagnoses, core biopsies (CBs) obtained from patients using coring needles (CNs) are traditionally visualized and assessed on microscope slides by pathologists after samples are processed and sectioned. A fundamental gain in optical information (i.e., diagnosis/staging) may be achieved when whole, unsectioned CBs (L = 5–20, D = 0.5–2.0 mm) are analyzed in 3D. This approach preserves CBs for traditional pathology and maximizes the diagnostic potential of patient samples. To bridge CNs/CBs with imaging, our group developed a microfluidic device that performs biospecimen preparation on unsectioned CBs for pathology. The ultimate goal is an automated and rapid point-of-care system that aids pathologists by processing tissue for advanced 3D imaging platforms. An inherent, but essential device feature is the microfluidic transport of CBs, which has not been previously investigated. Early experiments demonstrated proof-of-concept: pancreas CBs (D = 0.3–2.0 mm) of set lengths were transported in straight/curved microchannels, but dimensional tolerance and flow rates were variable, and preservation of CB integrity was uncontrolled. A second study used metal cylinder substitutes (L = 10, D = 1 mm) in microchannels to understand the transport mechanism. However, CBs are imperfectly shaped, rough, porous and viscoelastic. In this study, fresh/formalin-fixed porcine and human pancreas CBs were deposited into our device through a custom interface using clinical CNs. CB integrity (i.e., sample viability) may be assessed at every stage using an optomechanical metric: physical breaks were determined when specimen intensity profile data deviated beyond xavg + 2σ. Flow rates for human CBs were determined for several CNs, and microfluidic transport of fresh and formalin-fixed CBs was analyzed.

Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

“…Deficient production of digestive enzymes and hormones, as well pancreas blockage by tumors and gallstones, leads to subsequent malfunction of the entire digestive system and further compliances. Trying to solve these life-threatening conditions, researchers have made use of microfluidics to study and diagnose pancreatic cancer [ 125 , 126 , 127 , 148 ], culture pancreatic islets [ 112 , 113 , 114 , 138 ], monitor stimulus-secretion factors [ 139 , 140 , 143 ] and promote tissue-specific cell differentiation [ 124 ].…”