Pharmaceutical & medical
elements and/ or molecules in the sample into gaseous ions with or without fragmentation and then separating them in a mass analyser, the elements and/or molecules are charactersed by their mass-to-charge ratio (m/z), or location of the pulses, and relative abundance, or the amplitudes of the pulses, in the mass spectra. A mass spectrometer consists of three major components: the ion source for producing gaseous ions from the sample under test, the mass analyser for separating ions according to their m/z ratios, and the ion detector for detecting the ions and the relative abundance of each ion species. The detector output is conditioned and digitised to produce a mass spectrum. Several mass analysers with fundamentally different strategies for separating ions of different m/z values are available. Figure 1 shows major blocks of quadruple and TOF MS. In TOF MS, ions formed by a short ionisation event are accelerated by an electrostatic field so that ions of different m/z have the same kinetic energy but different velocities. The ions then travel over a field-free drift path and arrive at the detector with different flight time - the lighter ions arrive before the heavier ones do, as illustrated in Figure 2. In practice, the flight time of a pack of ions of the same m/z distributes to form a pulse that can be as narrow as a few hundred picoseconds (ps) due to differences in initial spatial distributions and energy (or velocity) in the acceleration region. Each pulse is the sum of signals corresponding to multiple independent ion arrival events and often is characterised by the full width at half-maximum (FWHM) parameter. A detector, such as a microchannel plate (MCP)
M
detector, detects incoming ions and produces an electric current of pulses. The electric current is recorded with a time-to-digital converter (TDC) or a high speed ADC. While TDC can be extremely fast down to a few ps, it has a limited dynamic range for registering the amplitude of the pulses. High speed ADCs can achieve two or more giga samples per second (GSPS) with 10-bit, 12-bit, or even higher bit resolution, allowing precise registration of both timing and amplitude of the pulses. This article will discuss important specifications of high speed ADCs that impact the performance of the TOF MS.
APPLICATIONS OF TOF MS TOF MS has gained significant interest since the 1990s when the matrix-assisted laser desorption and ionisation (MALDI) was invented and commercialised. The MALDI technology ionises the matrix molecules, typically organic acids, and vaporises the sample molecules at the same time with ultraviolet (UV) laser pulses from hundreds of ps to a few nanoseconds (ns). In the gas phase, the matrix molecules transfer protons to the sample molecules so that the sample molecules are protonated and become charged ions. Because the matrix absorbs most of the laser energy, molecules in the sample retain their
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ass spectrometry (MS) is an analytical technique for quantifying known/unknown molecules within a sample based on molecular weight. By ionising
BOOST TIME OF FLIGHT MASS SPECTROMETRY WITH LOW
NOISE, HIGH SPEED ADCS Time of flight mass spectrometry (TOF MS) has become a critical instrument for applications in many fields, especially for its irreplaceable role in clinical microbiology laboratories for bacterial identification. At the heart of TOF MS is the low noise, high speed analogue-to-digital converter (ADC). In this article, Guixue (Glen) Bu, systems design engineer at Analog Devices, reviews the fundamentals of TOF MS with a focus on its key parameters. This article discusses the relationship between TOF MS parameters and ADC specifications. Mixed-signal front-end (MxFE) ADCs demonstrate that low noise, high speed ADCs can greatly improve metrics of TOF MS including mass accuracy, mass resolution, and sensitivity.
Figure 1. Major blocks of quadruple and TOF MS.
integrity without fragmenting or decomposing, making MALDI the most compelling ionisation method for the analysis of biological macromolecules. With easy coupling between MALDI and TOF MS, unlimited mass range, high sensitivity, and high throughput, TOF MS has become an essential tool for biomedical research, drug discovery, and clinical applications where analytes are often macromolecules. Notably, MALDI TOF MS plays an irreplaceable role in clinical bacterial identification with its fastest turnaround time of four hours, compared to
72+ hours by conventional or other novel technologies. Short turnaround time is critical to the care and outcome of patients suffering from bacterial infections. Additional advantages of MALDI TOF MS include easy sample preparation, low operation cost, and the potential to identify some rare bacteria. With antimicrobial resistance posing a major threat to human health around the world, there is a trend for MALDI TOF MS as a point-of-care device.
Figure 2. An illustration of time of flight mass analyser.
KEY PARAMETERS OF TOF MS The ability of TOF MS to quantify the different analytes in the test samples depends on many factors, including choice of sample ionisation method, configuration, and timing characteristics of electric fields for accelerating and guiding the ions towards the ion detector, detector efficiency, and signal digitisation. We limit our discussion to key specifications of
January 2024 Instrumentation Monthly
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