[unreadable] We propose to develop a novel micromachined ultrasonic electrospray source which eliminates most, if not all, limitations of the conventional ESI technology, thereby providing scientists involved in biomedicine, functional proteomics and biomarker discovery with a unique MS interface for high throughput, ultrasensitive, and multiplexed analysis of proteins mixtures of biological significance. The proposed technology called AMUSE (Array of Micromachined UltraSonic Electrospray) ion source has potential for operation at low voltages with wide range of solvents, capable of minimizing the required sample size and improving sample utilization, and is inherently suitable for parallel, high throughput operation with multiplexing in the array format. Further, the ultrasonic electrospray source can be made inexpensive to be disposable since it is batch microfabricated using a simple process. We will design and fabricate the prototype(s) of the micromachined ultrasonic electrospray source array for use in mass spectrometric analysis of protein mixtures of biological relevance. We will test and optimize the performance of both ESI device concepts and to clearly quantify their potential advantages. We will evaluate the analytical performance of a time-of-flight mass spectrometer outfitted with the proposed micromachined ultrasonic electrospray source and compare it with existing commercial nanospray ion sources. Development of an improved electrospray source for protein mass spectrometry, as proposed here, would enable identification of new biomarkers of various human deceases, including various types of cancers. In addition, mass spectrometry is routinely used in drug development, and therefore the advancement of electrospray mass spectrometry will contribute directly to improvement in public health. [unreadable] [unreadable] [unreadable]