A compact multianalyte biosensing platform is reported, composed of an organic electrochemical transistor (OECT) microarray integrated with a pumpless "finger-powered" microfluidic, for quantitative screening of glucose, lactate, and cholesterol levels. A biofunctionalization method is designed, which provides selectivity towards specific metabolites as well as minimization of any background interference. In addition, a simple method is developed to facilitate multi-analyte sensing and avoid electrical crosstalk between the different transistors by electrically isolating the individual devices. The resulting biosensing platform, verified using human samples, offers the possibility to be used in easy-to-obtain biofluids with low abundance metabolites, such as saliva. Based on our proposed method, other types of enzymatic biosensors can be integrated into the array to achieve multiplexed, noninvasive, personalized point-of-care diagnostics.
Organic electrochemical transistors (OECTs) are receiving a great deal of attention as amplifying transducers for electrophysiology. A key limitation of this type of transistors, however, lies in the fact that their output is a current, while most electrophysiology equipment requires a voltage input. A simple circuit is built and modeled that uses a drain resistor to produce a voltage output. It is shown that operating the OECT in the saturation regime provides increased sensitivity while maintaining a linear signal transduction. It is demonstrated that this circuit provides high quality recordings of the human heart using readily available electrophysiology equipment, paving the way for the use of OECTs in the clinic.
A biosensing platform based on an organic transistor circuit for metabolite detection in highly complex biological media is introduced. The sensor circuit provides inherent background subtraction allowing for highly specific, sensitive lactate detection in tumor cell cultures. The proposed sensing platform paves the way toward rapid, label-free, and cost-effective clinically relevant in vitro diagnostic tools.
Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are twofold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.
There is increasing demand for direct in situ metabolite monitoring from cell cultures and in vivo using implantable devices. Electrochemical biosensors are commonly preferred due to their low‐cost, high sensitivity, and low complexity. Metabolite detection, however, in cultured cells or sensitive tissue is rarely shown. Commonly, glucose sensing occurs indirectly by measuring the concentration of hydrogen peroxide, which is a by‐product of the conversion of glucose by glucose oxidase. However, continuous production of hydrogen peroxide in cell media with high glucose is toxic to adjacent cells or tissue. This challenge is overcome through a novel, stacked enzyme configuration. A primary enzyme is used to provide analyte sensitivity, along with a secondary enzyme which converts H2O2 back to O2. The secondary enzyme is functionalized as the outermost layer of the device. Thus, production of H2O2 remains local to the sensor and its concentration in the extracellular environment does not increase. This “biostack” is integrated with organic electrochemical transistors to demonstrate sensors that monitor glucose concentration in cell cultures in situ. The “biostack” renders the sensors nontoxic for cells and provides highly sensitive and stable detection of metabolites.
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