Piezoelectric microcantilever serum protein detector

Joseph A. Capobianco

doi:10.17918/etd-2993

The development of a serum protein detector will provide opportunities for better screening of at-risk cancer patients, tighter surveillance of disease recurrence and better monitoring of treatment. An integrated system that can process clinical samples for a number of different types of biomarkers would be a useful tool in the early detection of cancer. Also, screening iomarkers such as antibodies in serum would provide clinicians with information regarding the patient's response to treatment. Therefore, the goal of this study is to develop a sensor which can be used for rapid, all-electrical, real-time, label-fee, in-situ, specific quantification of cancer markers, e.g., human epidermal receptor 2 (Her2)or antibodies, in serum. To achieve this end, piezoelectric microcantilever sensors (PEMS) were constructed using an 8 [mu]m thick lead magnesium niobate-lead titanate (PMN-PT) freestanding film as the piezoelectric layer. The desired limit of detection is on the order of pg/mL. In order to achieve this goal the higher frequency lateral extension modes were used. Also, as the driving and sensing of the PEMS is electrical, the PEMS must be insulated in a manner that allows it to function in aqueous solutions. The insulation layer must also be compatible with standardized bioconjugation techniques. Finally, detection of both cancer antigens and antibodies in serum was carried out, and the results were compared to a standard commercialized protocol. PEMS have demonstrated the capability of detecting Her2 at a concentration of 5 pg/mL in diluted human serum (1:40) in less than 1 hour. The approach can be easily translated into the clinical setting because the sensitivity is more than sufficient for monitoring prognosis of breast cancer patients. In addition to Her2 detection, antibodies in serum were assayed in order to demonstrate the feasibility of monitoring the immune response for antibody-dependent cellular cytotoxicity (ADCC) in patients on antibody therapies such as Herceptin and Cetuximab. The PEMS displayed a limit of detection of 100 fg/mL, which was 100 times lower than the current methods of protein detection in serum, such as ELISA. Furthermore, the sensitivity of the PEMS device allows it to be capable of determining the dissociation constant, Kd, of selective receptors such as antibodies. Using the dose response trials of Her2, Kd has been deduced for H3 scFv, and Herceptin, a commercial antibody specific for Her2.

Piezoelectric microcantilever serum protein detector

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Piezoelectric microcantilever serum protein detector

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