Testing cancer treatments relies mostly on trial and error; patients may undergo multiple time-consuming and hard-to-tolerate therapies in pursuit of one that works. Recent innovations in pharmaceutical development involve growing artificial tumors to test drugs on specific cancer types. These models take weeks to grow and don’t account for an individual patient’s biological makeup, which can affect treatment efficacy.
A 3D-printed microfluidic device was developed that simulates cancer treatments on biopsied tumor tissue so clinicians can examine how individual patients will respond to different therapeutics before administering a single dose. The device, which can be printed in about one hour, is a chip slightly larger than a quarter, with three cylindrical “chimneys” rising from the surface. These are ports used to input and drain fluids, as well as remove unwanted air bubbles. Biopsied tumor fragments are placed in a chamber connected to a network of channels that deliver fluids — containing, for instance, immunotherapy agents or immune cells — to the tissue. Clinicians can then use various imaging techniques to see how the tissue responds to the drugs.
A key feature was using a new biocompatible resin — traditionally used for dental applications — that can support long-term survival of biopsied tissue. Although previous 3D-printed microfluidics have held promise for drug testing, chemicals in their resin usually kill cells quickly. Fluorescence microscopy images show the device, called a tumor analysis platform (TAP), kept more than 90 percent of the tumor tissue alive for at least 72 hours, and potentially much longer.
The device could be rapidly implemented into clinical settings. Doctors could, for instance, print out a multiplexed device that could support multiple tumor samples in parallel to enable modeling of the interactions between tumor fragments and many different drugs, simultaneously, for a single patient. In the future, a physician with a 3D printer could print out the devices as needed. A promising application is testing immunotherapy, a new treatment method using certain drugs to rev up a patient’s immune system to help it fight cancer. The new device could help doctors better identify treatments to which an individual is likely to respond.
Microfluidics devices are traditionally manufactured via micromolding, using a rubberlike material called polydimethylsiloxane (PDMS). This technique, however, was not suitable for creating the three-dimensional network of features — such as carefully sized fluid channels — that mimic cancer treatments on living cells. Instead, 3D printing was used to craft a device “monolithically” — meaning printing an object all in one pass, without the need to assemble separate parts.
The heart of the device is Pro3dure GR-10 — a resin primarily used to make mouthguards that protect against teeth grinding. The material is nearly as transparent as glass, has barely any surface defects, can be printed in very high resolution, and does not negatively impact cell survival.