Radiant energy – Ionic separation or analysis
Reexamination Certificate
2000-05-11
2004-03-16
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
Reexamination Certificate
active
06707031
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a laser desorption ion source, and more particularly, to a laser optical bench for use with a laser desorption ion source that preferentially shapes a beam from a light source by predominantly focusing the beam in a single plane.
2. Description of the Prior Art
A laser desorption ion source is a device that utilizes the energy inherent in a focused laser beam to promote the desorption of neutrals and/or ions from solid or liquid state matter. In the case of solid matter, materials or samples of interest are presented as solid state crystals or thin films upon a sample support typically referred to as a probe. For liquid matter, the fluids are introduced as droplets or a fine spray and may be desorbed in stream or upon a physical support.
The energy transfer process may proceed through direct thermal or electronic excitation of the material or through indirect thermal excitation. If the material directly absorbs energy from the laser source and heats up via direct thermal or secondary thermal changes in response to electronic excitation, the process is known as laser-induced thermal desorption (LITD). If the material of interest receives thermal energy from neighboring compounds while being a member of a co-crystal or thin film matrix, the process is known as matrix-assisted laser desorption (MALD). If the material or sample of interest has been physically modified, extracted or amplified by the probe surface, or if the probe surface contains integral energy absorbing molecules capable of indirect energy transfer to the sample of interest, the process is known as surfaced enhanced laser desorption (SELD).
Should preferential ionization be created for the above described desorption motifs, then such processes are respectively referred to as laser desorption/ ionization (LDI), matrix-assisted laser desorption/ionization (MALDI), and surface enhanced laser desorption/ionization (SELDI).
Regardless of which energy transfer process is used, a laser desorption ion source primarily consists of a collection of components generally referred to as a laser optical bench. Such a laser optical bench is schematically represented in FIG.
1
.
Generally, a laser optical bench
10
includes a light source or photon source
11
, which is generally a continuous beam or pulsed laser, a beam splitter
12
, photodiode or other photodetector
13
, attenuator
14
, lens
15
, mirror
16
and target
17
, which is generally a probe including a sample of material of interest.
If a continuous beam laser is employed as light source
11
, desorption/ionization occurs with a constant duty cycle. If desired, high speed gating of the beam is typically achieved by using a shutter, which blocks the beam or a movable mirror that directs the beam into a beam dump (not shown). If a pulsed laser is employed as light source
11
, the duty cycle is dependent upon the pulse width and repetition rate. High speed gating of the beam is achieved by controlling the pulsing process.
In some situations, the laser optical bench may include a photodetector or photodiode
13
to measure the energy of the laser source or to detect the lasing event in the case of pulsed laser applications. Typically, optical beam splitter
12
is used to divide off a small fraction of the incident beam and direct it toward the appropriate photodetector. If the photodetector is used to measure delivered energy, it is usually of the thermal, photo-emissive, or semiconductor detector varieties. If the photodetector functions to detect the lasing event of a pulsed laser train, the photodetector is preferentially a small surface area semiconductor photodiode, which is capable of delivering very fast response times.
The propagated laser beam needs to be processed for the purposes of laser desorption. Such processing often involves control of laser energy, laser fluence (laser energy/unit area), and/or laser irradiance (radiant power/unit area). To achieve the latter, a combination of lenses and attenuation devices are often used. Typical laser energy attenuation devices include a mechanical iris, a neutral density filter or a fresnel reflection/refraction device. If a neutral density filter has a gradient of optical densities allowing for continuous adjustment of transmitted laser energy, it is referred to as a gradient neutral density filter (GNDF).
The ultimate size of the focused laser spot on the target is controlled through prudent selection of mirrors and lenses. Typically, a design that optimizes optical throughput while providing the desired fluence or irradiance dynamic range is employed. Additionally, the combination of attenuating and focusing elements should optimally create an image whose spatial distribution creates a desorption locus that promotes maximum sampling area while maintaining maximum ion extraction efficiency.
Increasing sampling area has three major advantages, specifically decreased analysis time, improved sample-to-sample reproducibility, and increased analytical sensitivity. The advantage of decreased analysis time is readily apparent and generally desirable. If one addresses a greater amount of sample area with each laser spot, a given sample region may be completely interrogated in less time than that required by approaches that employ smaller laser spots.
Typical sample preparation techniques for the previously noted laser desorption scheme inherently create solid-state or liquid samples with appreciable amounts of heterogeneity and microenvironmental differences. These differences are sources of qualitative and quantitative in reproducibility when assaying a plurality of identical samples. Although some approaches, such as SELDI, function to minimize these effects, statistically significant perturbations may still be observed. The employment of large laser probed regions improves reproducibility by increasing the area of sample investigated for each laser desorption event, statistically minimizing the effect of microheterogeneity.
The means by which target probed areas are enlarged is important with respect to sample laser irradiance. Generally speaking, sample desorption and ionization for the previously identified schemes occur at some threshold irradiance level. Furthermore, it is often desirable to have the ability to operate at levels significantly higher than threshold. Consequently, a given increase in laser spot area would require a concomitant increase in laser radiant power. Such laser radiant power increases may result in the need to employ more powerful and expensive laser sources. Accordingly, so, a means which increases the target sampling area that does not necessitate significant increases in laser radiant power is desired.
Increased analytical sensitivity is achieved by virtue of the fact that more sample is desorbed and ionized for each desorption event, assuming that the additional ionized material within the desorption cloud may be efficiently extracted. The desorption cloud can be considered to be a collection of ions, neutrals, and electrons capable of shielding externally applied electrical fields. It is generally recognized that ion extraction occurs within a given axial length of the desorption cloud known as the plasma skin depth. The plasma skin depth is that portion of a cloud's outer perimeter for which externally applied electric fields penetrate and do work upon charged particles. It is typically determined by the fundamental energetics of the desorption process and for a given set of conditions, is considered to be relatively dependent upon the cloud's charged particle density.
For the previously noted techniques, desorption cloud charge particle density has been determined to be dependent upon applied laser irradiance. Low irradiance levels produce clouds of nominal charged particle density. Under these conditions, the plasma skin depth can extend appreciably into the center of the desorption cloud and a vast majority of the desorbed ions can be efficiently extracted. In contrast, the appli
Bryan Raymond G.
Weinberger Scot R.
Ciphergen Biosystems Inc.
Kalivoda Christopher M.
Lee John R.
Townsend and Townsend / and Crew LLP
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