Fabrication and packaging of a dual sensing electrochemical biotransducer for glucose and lactate useful in intramuscular physiologic status monitoring

The design, microfabrication, packaging, surface functionalization and in vitro testing of a complete electrochemical cell-on-a-chip (ECC) that uses the microdisc electrode array (MDEA) working electrode design is presented. The device is for eventual intramuscular implantation as an electrochemical biotransducer for the continuous amperometric monitoring of glucose and lactate in a vertebrate animal trauma model. The microfabricated ECC MDEA5037 comprises two discrete electrochemical cells-on-a-chip, each with a shared reference electrode, a discrete counter electrode, and an MDEA working electrode. Each MDEA consists of 37 openings, each 50 μm in diameter, and separated within a hexagonal close packed array by center-on-center distances of 100 μm. The 4 mm by 2 mm biotransducer was packaged for implantation and electrochemical signal acquisition by mounting onto a ceramic chip carrier to which it was gold wire-bonded and the chip carrier soldered to a five-conductor, shielded, silicone insulated hookup wire. Robust first level packaging was developed to withstand harsh chemical, elevated temperature and plasma surface treatments. The use of cross-linked SU-8 as a second level packaging layer reduced the qualifying device failure rate from 90% to almost < 1% (n = 65). Finally, the packaged biotransducer was coated with a layer of bioactive hydrogel as a means to confer molecular recognition, specificity and biocompatibility in preparation for implantation. Cyclic Voltammetry (CV), Electrical Impedance Spectroscopy (EIS), and microscopic examination were performed for packaged biochip qualification.