A high speed mass spectrometer based on micromachined ion optics and position sensitive detection for the monitoring of non-stationary processes

A novel microfabrication method to make ion gates and a mass spectrometer using position sensitive detection has been implemented using Hadamard Transform multiplexing and was applied to the monitoring of protein unfolding. Hadamard time-of-flight mass spectrometry (HTTOFMS) is a technique that increases the signal-to-noise ratio (SNR) of mass spectrometric measurements by measuring more than one mass at a time. HTTOFMS is implemented by temporally modulating the intensity of a beam of ions created from the sample, and subsequently analyzing the instantaneous ion current at different detectors at the end of a flight tube. Ions are modulated using an interdigitated ion gate called a Bradbury Nielsen gate (BNG). We have developed a microfabrication method that enables the fabrication of robust silicon micromachined BNGs with wire spacings of 100 mum, 50 mum and 25 mum using standard dry etching techniques. After the ion beam is modulated, it is detected at the end of a flight tube using a counting detector. In the traditional HTTOFMS implementation, the ion current is measured at a single point in the detector plane, limiting the duty cycle of the technique to 50%. We have extended the duty cycle of the technique to 100% by implementing a dual anode position sensitive detector, enabling continuous detection of electrosprayed ions. We subsequently designed and constructed a new HTTOFMS instrument that combines microfabricated BNGs and a delay line anode imaging detector. This enabled the continuous imaging and counting of an ion beam in real time and the acquisition of spectra in the tens of milliseconds timescale. We measured applied this system to the real-time monitoring of the unfolding of cytochrome c using a newly designed kinetics apparatus at an effective rate of 100 spectra/second.