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We developed a MEMS based sensor, Nanopin, for mechanical characterization of individual adherent cells. Nanopin consists of sensing tip that forms a contact with a cell, a displacement sensor, and an actuator. The feasibility of sensing was evaluated using various concentrations of agarose gel, and then the stiffness measurements of human carcinoma cells were conducted on different surfaces. After the measurements of cells, we confirmed that cells grow normally in an incubator.

We report the successful demonstration of an on-chip tau detection system based on the difference in landing rate and binding density of microtubules (MTs) on a kinesin surface. Tau detection device comprises of a MT reservoir, channel and collector region with an overhang structure. We assayed MTs decorated with three tau types in the kinesin coated device. Since the increase in fluorescence intensity (FI) at the collector regions reflected the type of tau decorated on MTs, thus by measuring the FI we were able to distinguish wild 3R, 4R and P301L mutant tau.

Tau protein is a biomarker for neurodegeneration. The microtubule (MT)-tau binding affinity varies according to the type of tau isoform and their degree of phosphorylation. We have utilized the difference in binding affinity of tau protein to MT to be evaluated by kinesin motor protein based MT gliding system, in order to detect and differentiate tau isoforms and their mutants. Evaluation parameters are landing rate and density of MTs on a kinesin-coated surface, and their strong correlation enables us to measure only landing rate to distinguish 2N3R and 2N4R (tau isoforms) and mutants. Secondly; we designed and fabricated a microstructure to detect tau-attached MTs, which is composed of a reservoir, parallel channels and collectors. Increase of fluorescent intensity by accumulation of MTs over time was successfully detected at the collector areas. Sensitive and rapid MT-kinesin based detection of tau isoforms (3R/4R) and mutated tau proteins on a microchip format will aid in differential diagnosis and early detection of neurodegenerative condition such as Alzheimer disease (AD).

A microfluidics device to detect microtubule-binding proteins was proposed using microtubule-kinesin based system. To provide “proof of principle”, attachment of microtubule associated tau protein was detected via the change in kinesin velocity. The proposed device is capable of multiplex parallel assay of several experimental samples by using the same kinesin-coated beads moving in the same channel with immobilized microtubules. The results showed that the device successfully detected the hindered kinesin motion due to tau attachment on microtubule (MT) surface.

A molecular detection system was realized using the change in the characteristics of the kinesin-coated bead motion along protein-attached microtubules. A hybrid bio/microfluidics device with a microtubule immobilized main channel and protein-injected sub-channels allowed us to compare different protein attachments and several control experiments with the same experimental conditions. As kinesin/microtubule system is an essential component of neurons, the proposed device is a promising tool for diagnostics of several neurodegenerative diseases.