Disposable electrochemical sensor prepared using 3D printing for cell and tissue diagnostics

• Novel chip architecture of “all polymer” 3D electrochemical sensor was design and developed.
• In vitro monitoring directly from cell culture plate from 3 different colon cancer cell lines was demonstrated.
• This design is expected to offer portability and ease-of-use and will pave the way to serve as an important tool in the field of early detection and diagnosis.

In this paper we present a novel electrochemical sensor with a unique 3D architecture allowing for direct measurements on contact, or in close proximity, to biological samples. For biomedical applications, the all-polymer architecture can be mounted on special probes that can access the region under test with no need for biopsy as is done today with the conventional 2D electrodes. The chip consists of a biocompatible substrate comprised of an electrochemical cell with two gold electrodes (working and counter) and an Ag/AgCl quasi-reference electrode. The metal electrodes on the biochip front (sensing) side are fabricated by conventional electroplating and patterning methods. The chip itself is made from PDMS cast from a polymer master fabricated by 3D printing. The electrical communication between the biochip front and backside is enabled by through-hole via-contacts filled with conductive PDMS containing 60 wt% graphite powder. The electroactivity of working electrodes was verified by cyclic voltammetry of ferrocyanide/ferricyanide redox reaction. Amperometric in-vitro detection of the biomarker alkaline phosphatase from three different colon cancer cell lines directly in a cell culture plate while maintaining their biological environment was successfully demonstrated. The sensor exhibit stable voltammetric signatures and significant amperometric response to the enzyme in repeated tests. This approach paves the way to perform direct, non-invasive diagnostics on top of an exposed cell layer for both in-vivo and in-vitro applications.