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ABSTRACT: Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, boronic acid-containing hydrogels are being used in a variety of implantable glucose sensors under development, including sensors based on optical, fluorescence, and swelling pressure measurements. However, some method of glucose selectivity enhancement is often necessary, because isolated boronic acid molecules have a binding constant with glucose that is some forty times smaller than their binding constant with fructose, the second most abundant sugar in the human body. In many cases, glucose selectivity enhancement is obtained by incorporating pendant tertiary amines into the hydrogel network, thereby giving rise to a hydrogel that is zwitterionic at physiological pH. However, the mechanism by which incorporation of tertiary amines confers selectivity enhancement is poorly understood. In order to clarify this mechanism, we use the osmotic deswelling technique to compare the thermodynamic interactions of glucose and fructose with a zwitterionic smart hydrogel containing boronic acid moieties. We also investigate the change in the structure of the hydrogel that occurs when it binds to glucose or to fructose using the technique of small angle neutron scattering.
Sensors and Actuators B Chemical 12/2011; 160(1):1363-1371. · 3.90 Impact Factor
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ABSTRACT: Hydrogels have been demonstrated to swell in response to a number of external stimuli including pH, CO(2), glucose, and ionic strength making them useful for detection of metabolic analytes. To measure hydrogel swelling pressure, we have fabricated and tested novel perforated diaphragm piezoresistive pressure sensor arrays that couple the pressure sensing diaphragm with a perforated semi-permeable membrane. The 2×2 arrays measure approximately 3 × 5 mm(2) and consist of four square sensing diaphragms with widths of 1.0, 1.25, and 1.5 mm used to measure full scale pressures of 50, 25, and 5 kPa, respectively. An optimized geometry of micro pores was etched in silicon diaphragm to allow analyte diffusion into the sensor cavity where the hydrogel material is located. The 14-step front side wafer process was carried out by a commercial foundry service (MSF, Frankfurt (Oder), Germany) and diaphragm pores were created using combination of potassium hydroxide (KOH) etching and deep reactive ion etching (DRIE).Sensor characterization was performed (without the use of hydrogels) using a custom bulge testing apparatus that simultaneously measured deflection, pressure, and electrical output. Test results are used to quantify the sensor sensitivity and demonstrate proof-of-concept. Simulations showed that the sensitivity was slightly improved for the perforated diaphragm designs while empirical electrical characterization showed that the perforated diaphragm sensors were slightly less sensitive than solid diaphragm sensors. This discrepancy is believed to be due to the influence of compressive stress found within passivation layers and poor etching uniformity. The new perforated diaphragm sensors were fully functional with sensitivities ranging from 23 to 252 μV/V-kPa (FSO= 5 to 80mV), and show a higher nonlinearity at elevated pressures than identical sensors with solid diaphragms. Sensors (1.5×1.5 mm(2)) with perforated diaphragms (pores=40 μm) have a nonlinearity of approximately 10% while for the identical solid diaphragm sensor it was roughly 3 % over the entire 200 kPa range. This is the first time piezoresistive pressure sensors with integrated diffusion pores for detection of hydrogel swelling pressure have been fabricated and tested.
Sensors and Actuators A Physical 06/2010; 161(1-2):29-38. · 1.80 Impact Factor
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ABSTRACT: In the last few years, a new type of glucose-sensitive hydrogel (GSH) has been developed that shrinks with increasing glucose concentration due to the formation of reversible crosslinks The first osmotic swelling pressure results measured for any member of this new class of GSH are reported, so that their suitability for use in sensors combining pressure transducers and smart gels can be evaluated. Comparison is also made with results obtained for an older type of GSH that expands with increasing glucose concentration due to an increase in the concentration of counterions within the gel. The newer type of GSH exhibits both faster kinetics and weaker fructose interference, and therefore is more suitable for in vivo glucose sensing.
Sensors and Actuators B Chemical 01/2010; 144(1):332. · 3.90 Impact Factor
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ABSTRACT: We investigate thin films of "smart" polymer hydrogels used to convert miniature pressure sensors into novel chemomechanical sensors. In this versatile sensing approach, a smart hydrogel is confined between a porous membrane and the diaphragm of a piezoresistive pressure transducer. An increase in the environmental analyte concentration, as sensed through the pores of the membrane, is detected by measuring the change in pressure exerted by the hydrogel on the pressure transducer diaphragm. We compare the response of such a sensor with the response of a free-swelling hydrogel identical to the one used within the sensor. The sensor and the free hydrogel are observed to have comparable mean response times. However, the time-dependent response curve of the sensor, unlike that of the free hydrogel, is highly asymmetric between swelling and deswelling, with a smaller time constant for deswelling. We also investigate novel methods for increasing sensor sensitivity, such as use of a two-layer membrane with a nanoporous polymer inner layer, and pre-loading of the hydrogel under pressure. In ionic strength response tests, use of an inner membrane increases sensor sensitivity without increasing mean response time, an effect that varies with membrane water fraction.
Sensors and Actuators B Chemical 02/2009; 136(1):186. · 3.90 Impact Factor
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ABSTRACT: This report details the first experimental results from novel hydrogel sensor array (2 × 2) which incorporates analyte diffusion pores into a piezoresistive diaphragm for the detection of hydrogel swelling pressures and hence chemical concentrations. The sensor assembly was comprised of three components, the active four sensors, HPMA/DMA/TEGDMA (hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA)) hydrogel, and backing plate.Each of the individual sensors of the array can be used with various hydrogels used to measure the presence of a number of stimuli including pH, ionic strength, and glucose concentrations. Ideally, in the future, these sensors will be used for continuous metabolic monitoring applications and implanted subcutaneously. In this paper and to properly characterize the sensor assembly, hydrogels sensitive to changes ionic strength were synthesized using hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA) and inserted into the sensor assembly. This hydrogel quickly and reversibly swells when placed environments of physiological buffer solutions (PBS) with ionic strengths ranging from 0.025 to 0.15 M, making it ideal for proof-of-concept testing and initial characterization.The assembly was wire bonded to a printed circuit board and coated with 3 ± 0.5 μm of Parylene-C using chemical vapor deposition (CVD) to protect the sensor and electrical connections during ionic strength wet testing. Two versions of sensors were fabricated for comparison, the first incorporated diffusion pores into the diaphragm, and the second used a solid diaphragm with perforated backing plate.This new design (perforated diaphragm) was shown to have slightly higher sensitivity than solid diaphragm sensors with separate diffuse backing plates when coupled with the hydrogel. The sensitivities for the 1 mm × 1 mm, 1.25 mm × 1.25 mm, 1.5 mm × 1.5 mm perforated diaphragm sensors were 53.3 ± 6.5, 171.7 ± 8.8, and 271.47 ± 27.53 mV/V-M, respectively. These results show that perforations in the diaphragm can be used not only to allow the diffusion of analyte into the cavity but to increase mechanical stress in the piezoresistive diaphragm, thereby increasing sensor output signal.The time constants for swelling (τswelling) and contracting (τcontracting) were calculated by fitting the sensor output half cycles to an exponential growth function. We found that the sensors’ response was initially retarded during the preliminary hydrogel conditioning period then improved after 3–5 cycles with values of approximately 9 and 7 min for τswelling and τcontracting. For all sensors tested τswelling > τcontracting. This may be due to the increased loading on the hydrogel from the diaphragm during the swelling process. During contraction the diaphragm aids the hydrogel by reversibly applying mechanical pressure and therefore reducing τcontracting. Long term stability testing showed the sensors remained functional for upwards of 2 weeks in the test phosphate buffer solution (PBS).
Sensors and Actuators B: Chemical.
