3D printed conformal microfluidics for isolation and profiling of biomarkers from whole organs

Abstract

The ability to interface microfluidic devices with native complex biological architectures, such as whole organs, has the potential to shift the paradigm for the study and analysis of biological tissue. Here, we show 3D printing can be used to fabricate bio-inspired conformal microfluidic devices that directly interface with the surface of whole organs. Structured-light scanning techniques enabled the 3D topographical matching of microfluidic device geometry to porcine kidney anatomy. Our studies show molecular species are spontaneously transferred from the organ cortex to the conformal microfluidic device in the presence of fluid flow through the organ-conforming microchannel. Large animal studies using porcine kidneys (n = 32 organs) revealed the profile of molecular species in the organ-conforming microfluidic stream was dependent on the organ preservation conditions. Enzyme-linked immunosorbent assay (ELISA) studies revealed conformal microfluidic devices isolate clinically relevant metabolic and pathophysiological biomarkers from whole organs, including heat shock protein 70 (HSP-70) and kidney injury molecule-1 (KIM-1), which were detected in the microfluidic device as high as 409 and 12 pg mL, respectively. Overall, these results show conformal microfluidic devices enable a novel minimally invasive 'microfluidic biopsy' technique for isolation and profiling of biomarkers from whole organs within a clinically relevant interval. This achievement could shift the paradigm for whole organ preservation and assessment, thereby helping to relieve the organ shortage crisis through increased availability and quality of donor organs. Ultimately, this work provides a major advance in microfluidics through the design and manufacturing of organ-conforming microfluidic devices and a novel technique for microfluidic-based analysis of whole organs.

Electrochemical biosensors for pathogen detection

“…In particular, 3D printing has emerged as a useful fabrication platform for microfluidic-based analytical platforms (Waheed et al 2016). For example, to date, 3D printing has enabled the fabrication of electrode-integrated microfluidics (Erkal et al 2014), 3D microfluidics, organ-conforming microfluidics (Singh et al 2017a), and transducer-integrated microfluidics (Cesewski et al 2018). Thus, 3D printing may serve as an important fabrication platform for the creation of wearable microfluidic-based electrochemical biosensors for pathogen detection.…”

“…Challenges include biocompatibility (e.g., reduction of skin irritation), device power consumption, and biosensor-tissue mechanical and geometric matching. Because of the small sample size of body fluid secretions and the need to transport the sample to the electrode surface, microfluidic formats are now emerging for wearable bioanalytical systems (Singh et al 2017a).…”

Programming of Multicomponent Temporal Release Profiles in 3D Printed Polypills via Core–Shell, Multilayer, and Gradient Concentration Profiles

“…Pill Design and 3D Printing : Cylindrical pills of radius and height equal to 6.5 and 10 mm, respectively, were fabricated using a custom microextrusion 3D printing system . The system was composed of a gantry robot (F5200N.1; Fisnar), multiple dispensing systems (Ultimus V; Nordson), and a desktop computer.…”

3D Printed Biosensor Arrays for Medical Diagnostics

“…This facilitate the further investigation of multifunctional 3D printed devices that can express biomimetic activity in diagnostic applications. A bioinspired microfluidic chip that can be attached to whole organs was proposed by Singh et al [77]. This microfluidic chip was fabricated based on structured light scanning of the whole organ followed by stereolithographic 3D printing using the scanned conformation.…”