Piezoresistive Membrane Surface Stress Sensors for Characterization of Breath Samples of Head and Neck Cancer Patients.

For many diseases, where a particular organ is affected, chemical by-products can be found in the patient's exhaled breath. Breath analysis is often done using gas chromatography and mass spectrometry, but interpretation of results is difficult and time-consuming. We performed characterization of patients' exhaled breath samples by an electronic nose technique based on an array of nanomechanical membrane sensors. Each membrane is coated with a different thin polymer layer. By pumping the exhaled breath into a measurement chamber, volatile organic compounds present in patients' breath diffuse into the polymer layers and deform the membranes by changes in surface stress. The bending of the membranes is measured piezoresistively and the signals are converted into voltages. The sensor deflection pattern allows one to characterize the condition of the patient. In a clinical pilot study, we investigated breath samples from head and neck cancer patients and healthy control persons. Evaluation using principal component analysis (PCA) allowed a clear distinction between the two groups. As head and neck cancer can be completely removed by surgery, the breath of cured patients was investigated after surgery again and the results were similar to those of the healthy control group, indicating that surgery was successful.

Double-side-coated nanomechanical membrane-type surface stress sensor (MSS) for one-chip-one-channel setup.

With their capability for real-time and label-free detection of targets ranging from gases to biological molecules, nanomechanical sensors are expected to contribute to various fields, such as medicine, security, and environmental science. For practical applications, one of the major issues of nanomechanical sensors is the difficulty of coating receptor layers on their surfaces to which target molecules adsorb or react. To have measurable deflection, a single-side coating is commonly applied to cantilever-type geometry, and it requires specific methods or protocols, such as inkjet spotting or gold-thiol chemistry. If we can apply a double-side coating to nanomechanical sensors, it allows almost any kind of coating technique including dip coating methods, making nanomechanical sensors more useful with better user experiences. Here we address the feasibility of the double-side coating on nanomechanical sensors demonstrated by a membrane-type surface stress sensor (MSS) and verify its working principle by both finite element analysis (FEA) and experiments. In addition, simple hand-operated dip coating is demonstrated as a proof of concept, achieving practical receptor layers without any complex instrumentation. Because the double-side coating is compatible with batch protocols such as dip coating, double-side-coated MSS represents a new paradigm of one-chip-one-channel (channels on a chip are all coated with the same receptor layers) shifting from the conventional one-chip-multiple-channel (channels on a chip are coated with different receptor layers) paradigm.

Two dimensional array of piezoresistive nanomechanical Membrane-type Surface Stress Sensor (MSS) with improved sensitivity.

We present a new generation of piezoresistive nanomechanical Membrane-type Surface stress Sensor (MSS) chips, which consist of a two dimensional array of MSS on a single chip. The implementation of several optimization techniques in the design and microfabrication improved the piezoresistive sensitivity by 3~4 times compared to the first generation MSS chip, resulting in a sensitivity about ~100 times better than a standard cantilever-type sensor and a few times better than optical read-out methods in terms of experimental signal-to-noise ratio. Since the integrated piezoresistive read-out of the MSS can meet practical requirements, such as compactness and not requiring bulky and expensive peripheral devices, the MSS is a promising transducer for nanomechanical sensing in the rapidly growing application fields in medicine, biology, security, and the environment. Specifically, its system compactness due to the integrated piezoresistive sensing makes the MSS concept attractive for the instruments used in mobile applications. In addition, the MSS can operate in opaque liquids, such as blood, where optical read-out techniques cannot be applied.

Effects of surfactant and gentle agitation on inkjet dispensing of living cells.

Inkjet dispensing is a promising method for patterning cells and biomaterials for tissue engineering applications. In a novel approach, this work uses a biocompatible surfactant to improve the reliability of droplet formation in piezoelectric drop-on-demand inkjet printing of Hep G2 hepatocytes onto hydrogels. During a long printing process, cell aggregation and sedimentation within the inkjet reservoir can lead to inconsistent printing results. In order to improve repeatability, the effects of gentle agitation on cell sedimentation and aggregation within the inkjet reservoir were also investigated. Cell viability and proliferation when printed onto prepared collagen substrates were assessed using live/dead staining and the Alamar Blue metabolic assay. The addition of 0.05% Pluronic as a surfactant did not reduce cell viability, which remained above 95% 2 days after printing. The surfactant improved the reliability of droplet formation. Although gentle stirring of the inkjet reservoir was sufficient to maintain a cell suspension and reduce sedimentation, aggregation within the suspension continued to affect printing performance over a 180 min printing period.