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We introduce a lead zirconate titanate [PZT; Pb(Zr0.52Ti0.48)O3] microdiaphragm resonating sensor packaged in a polydimethylsiloxane chip. The proposed sensor can measure the density and viscosity of a liquid that is within the density and viscosity regime of blood (1.060 × 103 kg/m3, 3–4 cP). To verify the basic characteristics of the sensor, viscous solutions were prepared from glycerol and deionized water with a density in the range from 0.998 to 1.263 × 103 kg/m3 and a viscosity in the range from 1 to 1414 cP. We measured the frequency responses of the sensor before and after injecting the viscosity- and density-controlled liquid under the bottom of the microdiaphragm. The resonant frequencies in the (1,1) and (2,2) modes decreased linearly as a function of the liquid density in the range from 0.998 to 1.146 × 103 kg/m3 with a sensitivity of 28.03 Hz/kg·m−3 and 81.85 Hz/kg·m−3, respectively. The full width at half maximum had a logarithmic relationship with the liquid viscosity in the viscosity range from 1 to 8.4 cP. The quality factor (Q-factor) for the 50% glycerol/water mixture was determined to be greater than 20 for both the (1,1) and the (2,2) modes, indicating that the microdiaphragm resonating sensor is suitable for measuring the density and viscosity of a liquid within a density range from 0.998 to 1.1466 × 103 kg/m3 and a viscosity range from 1 to 8.4 cP. These density and viscosity ranges span the regime of possible changes of blood characteristics. The microdiaphragm resonating sensors were also tested with a real human serum to verify that the sensor is suitable for measuring the viscosity and density of blood. Therefore, the PZT microdiaphragm resonating sensor could be utilized for early diagnosis of diseases associated with changes in the physical properties of blood.

Given that reduced graphene oxide (rGO)-based biosensors allow disposable and repeatable biomarker detection at the point of care, we developed a wafer-scale rGO patterning method with mass productivity, uniformity, and high resolution by conventional micro-electro-mechanical systems (MEMS) techniques. Various rGO patterns were demonstrated with dimensions ranging from 5 μm up to several hundred μm. Manufacture of these patterns was accomplished through the optimization of dry etching conditions. The axis-homogeneity and uniformity were also measured to verify the uniform patternability in 4-inch wafer with dry etching. Over 66.2% of uniform rGO patterns, which have deviation of resistance within range of ±10%, formed the entire wafer. We selected amyloid beta (Aβ) peptides in the plasma of APP/PS1 transgenic mice as a study model and measured the peptide level by resistance changes of highly uniform rGO biosensor arrays. Aβ is a pathological hallmark of Alzheimer’s disease and its plasma concentration is in the pg mL−1 range. The sensor detected the Aβ peptides with ultra-high sensitivity; the LOD was at levels as low as 100 fg mL−1. Our results provide biological evidences that this wafer-scale high-resolution patterning method can be used in rGO-based electrical diagnostic devices for detection of low-level protein biomarkers in biofluids.

Detection of amyloid-β (Aβ) aggregates contributes to the diagnosis of Alzheimer disease (AD). Plasma Aβ is deemed a less invasive and more accessible hallmark of AD, as Aβ can penetrate blood-brain barriers. However, correlations between biofluidic Aβ concentrations and AD progression has been tenuous. Here, we introduce a diagnostic technique that compares the heterogeneous and the monomerized states of Aβ in plasma. We used a small molecule, EPPS [4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid], to dissociate aggregated Aβ into monomers to enhance quantification accuracy. Subsequently, Aβ levels of EPPS-treated plasma were compared to those of untreated samples to minimize inter- and intraindividual variations. The interdigitated microelectrode sensor system was used to measure plasma Aβ levels on a scale of 0.1 pg/ml. The implementation of this self-standard blood test resulted in substantial distinctions between patients with AD and individuals with normal cognition (NC), with selectivity and sensitivity over 90%.

A highly transparent conductive electrically-doped CVD-graphene electrode and its application in 365 nm light-emitting diodes.

Sensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer’s disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.