Researchers at the Swiss Federal Institute of Technology (EPFL) in Lausanne, Switzerland, the Universitá degli Studi di Genova in Italy, and the Institute for Research in Biomedicine (IRB) in Bellinzona, Switzerland, have been studying ways to develop biocompatible packaging for implantable devices to be used for remote monitoring of metabolites, such as glucose and lactate, and drugs.1,2,3,4 They designed a fully implantable sensor device consisting of a microfabricated sensing platform, custom designed integrated circuits (ICs), and a coil for power and data transmission. The device is powered through an inductive link between an external power coil and the coil embedded within the device. Metabolic readings are captured by the sensors and transmitted from the device to an external receiver. The three subcomponents were to be assembled into an integrated device and then encased in a biocompatible package prior to implantation in mice.
Key Parameters and Requirements
The goal of the research team’s latest study was to assess the biocompatibility of three different multi-panel sensor devices.1 The three prototypes varied in their shape, size, and the structure and composition of the device packaging. Additionally, two of the devices were implanted in the backs of the mice while the third was implantable in the peritoneum.
In one of the prototypes, Master Bond EP42HT-2Med was used both in the assembly of the sensor device and in the formulation of a biocompatible outer membrane for the device. EP42HT-2Med was used as an adhesive to join the substrate containing the electronics (ICs and antenna) with the sensing platform and as a glob top to protect the aluminum wire bonds that connect the electronics with the pads of the sensing platform. The outer membrane, which consisted of a mixture of EP42HT-2Med and polyurethane (PU), was applied by dip-coating the device three times at intervals of one hour. To ensure biocompatibility, the coated device was kept overnight at room temperature and then subjected to a temperature of 80°C for two hours to complete the cure process. After curing, the device was kept at room temperature overnight and then stored in phosphate-buffered saline (PBS) for an additional 24 hours.
All three prototypes were implanted in cavities created in two-month old male mice. After 30 days, the implants were removed, the implant sites were rinsed with PBS, and the liquid collected from each site was centrifuged and examined. The percentage of neutrophils and concentration of adenosine triphosphate (ATP), both of which serve as indicators of local inflammation, collected in the liquid from each prototype were measured and compared to the levels of neutrophils and ATP produced by control conditions. Control conditions included a cavity absent an implant, a cavity implanted with a biocompatible commercial chip, and a cavity injected with bacterial lipopolysaccharides (LPS).
Research findings indicated that each of the two prototypes implanted in the back, including the one that used EP42HT-2Med, was tolerated by the host after 30 days of implantation, while the device implanted in the peritoneum was rejected. ATP and neutrophil levels for each of the accepted prototypes were comparable to those of the negative controls (i.e., the empty cavity and the commercial chip) and were well below those of the positive control (i.e., the LPS-filled cavity).
The researchers concluded that the PU membrane enhanced with Master Bond EP42HT-2Med presents the best solution because it provides effective biocompatible coverage and a more reliable, more reproducible deposition process than the method used to add the protective membrane to the sensing platform in the other biocompatible prototype.