A microsensor system to probe physiological environments and tissue response

Abstract

Foreign body responses and bio-fouling caused by the physiological environment impair sensor performance due to alteration of the sensor/tissue interface. For in vivo applications longterm stability is a critical prerequisite and often affected due to host response towards the implant. In order to assess tissue response towards implants, we propose continuous measurements at the implant/tissue interface employing a microsensor device placed in contact with the chorioallantoic membrane (CAM) of the avian embryo. We introduce a biostable microsensor implant (MSI) to measure oxygen, pH and electrical impedance in situ. These parameters were chosen for their sensitivity with respect to the composition and properties of biological tissue. Micro fabrication technology in combination with electrochemical electrode functionalization was used to combine all sensors in a small planar array. The chorioallantoic membrane assay (CAM-assay) of avian ex ovo cultures served as a quasi-in vivo environment. Here we established an immuneactive and -deficient in vivo model, enabling comparison between weak and strong immune responses in the same organism. A miniaturized potentiostat unit ("MiniPot") was developed for controlling the MSI in humid culture environments. Here we performed continuous measurements of all sensor parameters at the implant/tissue interface with the microsensor device placed in contact with the CAM of the avian embryo.

A programmable energy efficient readout chip for a multiparameter highly integrated implantable biosensor system

“…To further improve the quality of the acquired data, a number of up to 128 "single measurements" are preformed and then averaged in order to obtain a measurement sample. This way random spikes or erratic data points are eliminated, which are generated due the fluctuating nature of the chemical reaction taking place between the electrode surface and the connected tissue (Lindner et al, 1986). The measurement samples form a "measurement sequence", which would eventually settle to a final value.…”

“…The measurement samples form a "measurement sequence", which would eventually settle to a final value. The number of samples and the final value are determined by the external microcontroller according to the criteria set by the International Union of Pure and Applied Chemistry (IUPAC;Lindner et al, 1986). The aforementioned concept is illustrated in Fig.…”

“…In the case of O 2 and temperature measurement, the measured analog signals are currents, where for the former a three electrode measurement setup is implemented and current flowing between the working electrode and the counter electrode is of interest (Kubon et al, 2010). For temperature measurements, an external Schottky diode is reversed biased and used as a transducer, where the reverse current is a measure of the temperature and the sensitivity of the sensor is controlled by the reverse bias voltage.…”

“…For monitoring of neuronal and metabolic activity a readout chip has to be implemented, which controls the data acquisition and management. In case of biosensor applications like subcutaneous metabolic monitoring, the electrochemical detection of ions, oxygen and pH requires a precise setting and measurement of voltage and currents at the metallic microelectrodes (Kubon et al, 2010;Jafari et al, 2014). For applications where large batteries and cabling is not suitable, stringent requirements on the readout chip in terms of size and energy efficiency are placed.…”

The Expanding World of Tissue Engineering: The Building Blocks and New Applications of Tissue Engineered Constructs

“…The next generation would also incorporate structures that would actively measure the health of the implant. Such lab on a chip applications in vivo , could improve the quality of monitoring available for implant systems [205]. Also developments in disease models and body-on-a-chip applications and demands in biorobotics will create new requirements for the next generation of tissue engineered constructs which will necessitate more widespread use of new methodologies such as pathway engineering or use of alternative cell sources.…”