Enzyme-Functionalized Piezoresistive Hydrogel Biosensors for the Detection of Urea.

Urea is used in a wide variety of industrial applications such as the production of fertilizers. Furthermore, urea as a metabolic product is an important indicator in biomedical diagnostics. For these applications, reliable urea sensors are essential. In this work, we present a novel hydrogel-based biosensor for the detection of urea. The hydrolysis of urea by the enzyme urease leads to an alkaline pH change, which is detected with a pH-sensitive poly(acrylic acid-co-dimethylaminoethyl methacrylate) hydrogel. For this purpose, the enzyme is physically entrapped during polymerization. This enzyme-hydrogel system shows a large sensitivity in the range from 1 mmol/L up to 20 mmol/L urea with a high long-term stability over at least eight weeks. Furthermore, this urea-sensitive hydrogel is highly selective to urea in comparison to similar species like thiourea or N-methylurea. For sensory applications, the swelling pressure of this hydrogel system is transformed via a piezoresistive pressure sensor into a measurable output voltage. In this way, the basic principle of hydrogel-based piezoresistive urea biosensors was demonstrated.

Hydrogel-Based Sensors for Ethanol Detection in Alcoholic Beverages.

A fast and reliable determination of the ethanol concentration is essential in the analysis of alcoholic beverages. However, different factors like pH value or salt concentration can influence the ethanol measurement. Furthermore, analytical figures of merit for the alcohol sensor, such as limit of detection, sensitivity and measurement uncertainty, are necessary for the application. In this paper, a detailed sensor characterization of a novel sensor based on ethanol-sensitive poly acrylamide hydrogels will be presented. The resulting swelling pressure of the hydrogel was transformed via a piezoresistive pressure sensor into a measurable output voltage. These kinds of sensors can be used over a large measuring range, up to 50 vol% ethanol and more, with a high sensitivity. In the range from pH 7.4 to 4, the pH value had no influence on the sensor signal. Higher salt concentrations can slightly influence the measurement. The detection limit amounts to 0.06⁻0.65 vol% ethanol. The concentration of a vodka sample was determined with a sufficient measuring uncertainty.

Piezoresistive Hydrogel-Based Sensors for the Detection of Ammonia.

Ammonia is an essential key compound in the chemical industry. However, excessively high ammonia concentrations can be harmful to the environment. Sensors for the detection of ammonia are therefore particularly important for environmental analysis. In this article, a novel hydrogel-based piezoresistive ammonia sensor is presented. In aqueous solution, ammonia reacts as a base. This alkaline pH change can be detected with stimuli-sensitive hydrogels. For such an application, highly sensitive hydrogels in the alkaline range with sufficient mechanical stability for the sensor application has to be developed. These conditions are fulfilled by the presented hydrogel system based on acrylic acid (AAc) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The hydrogel composition has a significant influence on the swelling behavior of the gel. Furthermore, the hydrogel swelling in ammonia solutions was tested and a detection limit in the range of 1 mmol/L ammonia depending on the buffer solution was determined. Ammonia-sensitive hydrogels can be used multiple times due to the repeatable swelling of the gel over several swelling cycles. To generate a measurable output voltage, the swelling pressure of ammonia-sensitive hydrogels were detected by using piezoresistive pressure sensors. All results of the free hydrogel swelling were verified in the sensor application. This low-cost ammonia sensor with a high sensitivity could be interesting for industrial chemical and biotechnological applications.

Hydrogel-Based Plasmonic Sensor Substrate for the Detection of Ethanol.

The in-line monitoring of ethanol concentration in liquids is a crucial part of process monitoring in breweries and distilleries. Current methods are based on infrared spectroscopy, which is time-consuming and costly, making these methods unaffordable for small and middle-sized companies. To overcome these problems, we presented a small, compact, and cost-effective sensing method for the ethanol content, based on a nanostructured, plasmonically active sensor substrate. The sensor substrate is coated with an ethanol-sensitive hydrogel, based on polyacrylamide and bisacrylamide, which induces a change in the refractive index of the substrate surface. The swelling and shrinking of such hydrogels offer a means to measure the ethanol content in liquids, which can be determined in a simple transmittance setup. In our study, we demonstrated the capability of the sensor principle for the detection of ethanol content ranging from 0 to 30 vol% ethanol. Furthermore, we determined the response time of the sensor substrate to be 5.2 min, which shows an improvement by a factor of four compared to other hydrogel-based sensing methods. Finally, initial results for the sensor's lifetime are presented.

Smart hydrogel based microsensing platform for continuous glucose monitoring.

In this paper, we present preliminary results showing the response of glucose-sensitive hydrogels, confined in micro-pressure sensors, to the changes in environmental glucose concentration. The glucose concentrations were incrementally varied between 20 and 0mM in 0.15M PBS solution at 7.4 pH and bovine serum at 7.4 pH at room temperature and response of the sensor was recorded. The micro sensors demonstrate a response time of 10 minutes in both PBS and serum. Tissue response after 55 days of subcutaneous implantation of a EtO sterilized sensor in mice is presented. The preliminary analysis of the surrounding tissue shows inflammation which is believed not to interfere with the sensor performance.

In-vitro investigations of a pH- and ionic-strength-responsive polyelectrolytic hydrogel using a piezoresistive microsensor.

Environmental responsive or smart hydrogels show a volume phase transition due to changes of external stimuli such as pH or ionic strength of an ambient solution. Thus, they are able to convert reversibly chemical energy into mechanical energy and therefore they are suitable as sensitive material for integration in biochemical microsensors and MEMS devices. In this work, micro-fabricated silicon pressure sensor chips with integrated piezoresistors were used as transducers for the conversion of mechanical work into an appropriate electrical output signal due to the deflection of a thin silicon bending plate. Within this work two different sensor designs have been studied. The biocompatible poly(hydroxypropyl methacrylate-N,N-dimethylaminoethyl methacrylate-tetra-ethyleneglycol dimethacrylate) (HPMA-DMA-TEGDMA) was used as an environmental sensitive element in piezoresistive biochemical sensors. This polyelectrolytic hydrogel shows a very sharp volume phase transition at pH values below about 7.4 which is in the range of the physiological pH. The sensor's characteristic response was measured in-vitro for changes in pH of PBS buffer solution at fixed ionic strength. The experimental data was applied to the Hill equation and the sensor sensitivity as a function of pH was calculated out of it. The time-dependent sensor response was measured for small changes in pH, whereas different time constants have been observed. The same sensor principal was used for sensing of ionic strength. The time-dependent electrical sensor signal of both sensors was measured for variations in ionic strength at fixed pH value using PBS buffer solution. Both sensor types showed an asymmetric swelling behavior between the swelling and the deswelling cycle as well as different time constants, which was attributed to the different nature of mechanical hydrogel-confinement inside the sensor.

Hydrogel-based piezoresistive pH sensors: investigations using FT-IR attenuated total reflection spectroscopic imaging.

The strong swelling ability of the pH-responsive poly(acrylic acid)/poly(vinyl alcohol) (PAA/PVA) hydrogel makes the development of a new type of sensor possible, which combines piezoresistive-responsive elements as mechanoelectrical transducers and the phase transition behavior of hydrogels as a chemomechanical transducer. The sensor consists of a pH-responsive PAA/PVA hydrogel and a standard pressure sensor chip. However, a time-dependent sensor output voltage mirrors only the physical swelling process of the hydrogel but not the corresponding chemical reactions. Therefore, an investigation of the swelling behavior of this hydrogel is essential for the optimization of sensor design. In this work, Fourier transform infrared (FT-IR) spectroscopic imaging was used to study the swelling of the hydrogel under in situ conditions. In particular, laterally and time-resolved FT-IR images were obtained in the attenuated total reflection mode and the entire data set of more than 80,000 FT-IR spectra was evaluated by principal component analysis (PCA). The first and third principal components (PCs) indicate the swelling process. Molecular changes within the carboxyl groups were observed in the second and fourth PC and identified as key processes for the swelling behavior. It was found that time-dependent molecular changes are similar to the electrical sensor output signal. The results of the FT-IR spectroscopic images render an improved chemical sensor possible and demonstrate that in situ FT-IR imaging is a powerful method for the characterization of molecular processes within chemical-sensitive materials.