Piezoresistive Microcantilever Biosensor Research Articles

A Flexible PI/Si/SiO2 Piezoresistive Microcantilever for Trace-Level Detection of Aflatoxin B1.

In this paper, a polyimide (PI)/Si/SiO2-based piezoresistive microcantilever biosensor was developed to achieve a trace level detection for aflatoxin B1. To take advantage of both the high piezoresistance coefficient of single-crystal silicon and the small spring constant of PI, the flexible piezoresistive microcantilever was designed using the buried oxide (BOX) layer of a silicon-on-insulator (SOI) wafer as a bottom passivation layer, the topmost single-crystal silicon layer as a piezoresistor layer, and a thin PI film as a top passivation layer. To obtain higher sensitivity and output voltage stability, four identical piezoresistors, two of which were located in the substrate and two integrated in the microcantilevers, were composed of a quarter-bridge configuration wheatstone bridge. The fabricated PI/Si/SiO2 microcantilever showed good mechanical properties with a spring constant of 21.31 nN/μm and a deflection sensitivity of 3.54 × 10−7 nm−1. The microcantilever biosensor also showed a stable voltage output in the Phosphate Buffered Saline (PBS) buffer with a fluctuation less than 1 μV @ 3 V. By functionalizing anti-aflatoxin B1 on the sensing piezoresistive microcantilever with a biotin avidin system (BAS), a linear aflatoxin B1 detection concentration resulting from 1 ng/mL to 100 ng/mL was obtained, and the toxic molecule detection also showed good specificity. The experimental results indicate that the PI/Si/SiO2 flexible piezoresistive microcantilever biosensor has excellent abilities in trace-level and specific detections of aflatoxin B1 and other biomolecules.

Highly sensitive microcantilever biosensors with enhanced sensitivity for detection of human papilloma virus infection

This paper demonstrates a piezoresistive microcantilever biosensor for a potential of the early detection of HPV infection. Gold was patterned on the top surface of the microcantilever to define the sensing area. Then, a self-assembled monolayer (SAM) was coated on the gold surface for the attachment of a gold binding protein (GBP) which was functionally activated with carboxyl groups and amine groups to bind probe molecules such as antibodies, oligonucleotide probes, DNA, and proteins. The surface-activated magnetic beads were introduced to the sensing area with DNA fragments of the HPV-infected cells. The magnetic force was induced to the surface-activated magnetic beads bound with probe molecules and HPV DNA fragments by placing a permanent magnet. The electrical signal output measured from the piezoresistive sensor integrated in the microcantilever was amplified 1000 times compared with non-HPV solution with a high SN ratio.

Direct determination of a small-molecule drug, valproic Acid, by an electrically-detected microcantilever biosensor for personalized diagnostics.

Direct, small-molecule determination of the antiepileptic drug, valproic acid, was investigated by a label-free, nanomechanical biosensor. Valproic acid has long been used as an antiepileptic medication, which is administered through therapeutic drug monitoring and has a narrow therapeutic dosage range of 50–100 μg·mL−1 in blood or serum. Unlike labeled and clinically-used measurement techniques, the label-free, electrical detection microcantilever biosensor can be miniaturized and simplified for use in portable or hand-held point-of-care platforms or personal diagnostic tools. A micromachined microcantilever sensor was packaged into the micro-channel of a fluidic system. The measurement of the antiepileptic drug, valproic acid, in phosphate-buffered saline and serum used a single free-standing, piezoresistive microcantilever biosensor in a thermally-controlled system. The measured surface stresses showed a profile over a concentration range of 50–500 μg·mL−1, which covered the clinically therapeutic range of 50–100 μg·mL−1. The estimated limit of detection (LOD) was calculated to be 45 μg·mL−1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL−1. Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.

Effect of p-type and n-type piezoresistors on characteristics of high sensitive silicon piezoresistive microcantilever designs

This study presents four new silicon piezoresistive microcantilevers designs for biosensor application and compares their surface stress sensitivities for p-type and n-type piezoresistors. One basic and three variant designs with the piezoresistor inscribing the rectangular holes are proposed. The piezoresistors are placed in the high stress concentration regions near the cantilever base for achieving maximum sensitivity. Mathematical models for cantilever deflection and piezoresistor stress are derived and verified using finite element software. The designs are studied for operating conditions involving surface stress, ambient temperature and operating voltages. Results show that the average longitudinal stress in the piezoresistor of variant models is more than three times the average transverse ones, and that p-type cantilevers are better than n-type in piezoresistive microcantilever biosensor application.

Detection of the antiepileptic drug phenytoin using a single free-standing piezoresistive microcantilever for therapeutic drug monitoring

Phenytoin, one of the most widely used antiepileptic drugs, suppresses the abnormal brain activity often seen in seizures. In this study, we report the electrical detection of phenytoin as an antiepileptic medication with a narrow therapeutic dosage range to which therapeutic drug monitoring (TDM) is applied. The measurement technique used an electrical detection of a piezoresistive microcantilever biosensor. This label-free, electrically measured microcantilever can be miniaturized in order to be portable for point-of-care, personal diagnosis or for personalized therapeutic drug monitoring. The miniaturized piezoresistive microcantilever was fabricated by micro-electro-mechanical system processes, and was integrated into a microfluidic channel with a system for label-free detection. The microcantilever biosensor was approved for the detection of phenytoin in solutions of deionized water and 100% fetal bovine serum. A linear profile in a drug-concentration range of 10–80μg/mL was detected, with the signal resolution being about 0.005Ω. The concentration sensitivity was 2.94×10−6(μg/mL)−1. The binding affinity (KD) was calculated to be 58μg/mL. The results of the present piezoresistive microcantilever biosensors showed a solid correlation of phenytoin drug detection with that in the clinically used fluorescence polarization immunoassay (FPIA).

Electrical detection of C-reactive protein using a single free-standing, thermally controlled piezoresistive microcantilever for highly reproducible and accurate measurements.

This study demonstrates a novel method for electrical detection of C-reactive protein (CRP) as a means of identifying an infection in the body, or as a cardiovascular disease risk assay. The method uses a single free-standing, thermally controlled piezoresistive microcantilever biosensor. In a commonly used sensing arrangement of conventional dual cantilevers in the Wheatstone bridge circuit, reference and gold-coated sensing cantilevers that inherently have heterogeneous surface materials and different multilayer structures may yield independent responses to the liquid environmental changes of chemical substances, flow field and temperature, leading to unwanted signal disturbance for biosensing targets. In this study, the single free-standing microcantilever for biosensing applications is employed to resolve the dual-beam problem of individual responses in chemical solutions and, in a thermally controlled system, to maintain its sensor performance due to the sensitive temperature effect. With this type of single temperature-controlled microcantilever sensor, the electrical detection of various CRP concentrations from 1 μg/mL to 200 μg/mL was performed, which covers the clinically relevant range. Induced surface stresses were measured at between 0.25 N/m and 3.4 N/m with high reproducibility. Moreover, the binding affinity (KD) of CRP and anti-CRP interaction was found to be 18.83 ± 2.99 μg/mL, which agreed with results in previous reported studies. This biosensing technique thus proves valuable in detecting inflammation, and in cardiovascular disease risk assays.

Stepped piezoresistive microcantilever designs for biosensors

The sensitivity of a piezoresistive microcantilever biosensor strongly depends on its ability to convert the surface stress-induced deflections into large resistance change. To improve the sensitivity, we present stepped microcantilever biosensor designs that show significant resistance change compared with commonly used rectangular designs. The cantilever is made of silicon dioxide with a u-shaped silicon piezoresistor. The surface stress-induced deflections, bimorph deflection, fundamental resonant frequency and self-heating properties of the cantilever are studied using the FEM software. The surface stress-induced deflections are compared against the analytical model derived in this work. Results show that stepped designs have better signal-to-noise ratio than the rectangular ones and cantilevers with l/L between 0.5 and 0.75 are better designs for improving sensitivity.

A conduction–convection model for self-heating in piezoresistive microcantilever biosensors

Thermal drifting caused by the self-heating in piezoresistive microcantilever biosensors is a major source of inaccuracy. To this use, the present study derives a simple and accurate conduction–convection model to predict the temperature distribution in p-doped piezoresistive microcantilevers because of self-heating. The model is applied to a 4-layer gold-coated piezoresistive silicon dioxide microcantilever biosensor with u-shaped silicon piezoresistor. The analytical results are compared to the numerical results. The effect of convective heat transfer coefficient on temperature profile is also studied. The comparison results show the analytical and numerical results are accurate within 4%. The sensitivity results showed that the resistance change produced by thermal drifting is about five-to-eight times that by the surface stress. Finally, the cantilever temperature profile is found to be strongly affected by the piezoresistor size and the convective heat transfer coefficient.