WO2007033432A1

WO2007033432A1 - Solid state laser and resonator

Info

Publication number: WO2007033432A1
Application number: PCT/AU2006/001396
Authority: WO
Inventors: Hamish Ogilvy; Jim Piper
Original assignee: Macquarie University
Priority date: 2005-09-23
Filing date: 2006-09-25
Publication date: 2007-03-29

Abstract

A method of detecting a target element of an associated background material is provided. The method comprising the steps of attaching a fluorescent label to the target element and then exposing the background material to a light beam from a laser which is designed to preferentially excite the fluorescent label for detection of the target element.

Description

SOLID STATE LASER AND RESONATOR

FIELD OF THE INVENTION

The present invention relates broadly to a resonator, a solid-state laser, and a laser beam wavelength conversion device and relates particularly, though not exclusively, to the laser and conversion device used to produce a stimulating light source. The invention also relates to a method of detecting target elements of an associated background material, and a method of writing a Bragg grating in an optical waveguide, for example, an optical fibre.

BACKGROUND OF THE INVENTION

Fluorescence based techniques provide a powerful means for both the qualitative and quantitative detection of biomolecules. Fluorescence techniques can provide exquisite sensitivity, sufficient for the detection of a single molecule when conditions are optimised, however fluorescent labels can lose much of their discriminatory power when viewed in the presence of autofluorescence. Organic and inorganic autofluorophores are in nature and some materials fluoresce with great intensity, obscuring or diminishing the visibility of synthetic fluorescent labels. Spectral selection techniques (emission and excitation filters) are useful in suppressing autofluorescents but are not always applicable due to the abundance and spectral range of autofluorophores. Fluorescent labels with long fluorescence lifetimes afford a means to resolve probe luminescence in the temporal domain using time resolved fluorescence. Lanthanide (including Eu⁺⁺ or Tb⁺*) chelate fluorescent probes have exceptionally long fluorescence lifetimes reaching milliseconds in some compounds. The very large difference in lifetimes is conveniently exploited using time resolved fluorescence to eliminate background signal and permit detection electronics to operate at maximum gain. Time resolved fluorescence instrumentation designed to capture only long lived fluorescence emission is technically simple and well suited to suppress autofluorescence.

Time domain techniques (also known as pulse fluorometry) rely on a brief excitation pulse of light to excite fluorescence emission from the sample. The excitation pulse should ideally terminate with a rapid falling edge to ensure that the time dependent fluorescent emission can be captured free of excitation energy. Certain lanthanide metal chelates have exceptionally long fluorescence lifetimes and the large difference in lifetimes enables effective suppression of background, greatly enhancing detection efficiency. Less than 1% of microrganisms found in the environment respond to culture and the detection of rare organisms using conventional fluorescent techniques can be exceptionally difficult. Time resolved fluorometry techniques are particularly advantageous in the detection of rare events since the method results in a high contrast labelled target against a near void background, greatly increasing the likelihood of detection.

Early time domain researchers employed chopper wheels as inexpensive pulsed excitation sources, however the pulse profile was characterised by a slow rising and falling edge that limited resolution and sensitivity of instruments. Other limitations of choppers include the inflexible nature of the pulse regime, inefficient use of light energy and the potential for image blur arising from drive motor vibration. Nitrogen lasers have found favour as a pulsed excitation source since they omit short (nanosecond) powerful pulses in the ultraviolet (UV 337 run) and are relatively inexpensive. The low repetition rate of N₂ lasers (10-60Hz) is a significant detraction and their rapid high voltage discharge radiates an intense electromagnetic pulse that can cause instrumentation problems. Helium cadmium (HeCd) lasers are continuous wave sources of UV that can be controlled by quartz acousto-optical modulation to generate the required short UV pulses for lanthanide chelate time resolved fluorescence studies. Although their capital cost is low, these laser sources are very inefficient. Platinum and palladium porphyrin fluorophores have shorter lifetimes (less than 100 βs) and they can be excited in the blue or violet spectral region, permitting the use of readily available argon iron lasers (488 nrn) coupled with an acousto-optic modulator. Gas discharge lasers require substantial electrical power input and generate significant heat that must be dissipated. Furthermore, the acousto-optic modulator requires a high voltage radio frequency drive signal and only a small portion of the input laser beam is modulated and available for sample excitation. Gas discharge laser excitation systems are bulky, expensive and relatively unreliable.

Fibre Bragg gratings are a periodic modulation of the refractive index of the optical fibres refractive index, and can be configured for a wide variety of useful applications including optical filters, wavelength division multiplexers and demultiplexers, and light delivery systems. It is known that these gratings can be written using near-UV light from an argon-ion laser. Fibre gratings can be manufactured by illuminating GeO₂ doped fibre from the side by use of the holographic phase mask technique, the mask having a period of about one micron. The fibre is striped first, then illuminated through the mask with the output from the argon ion laser. Typically, cylindrical lens of fused silica with an approximate focal length of 5 cm focuses the laser light to a typical writing intensity of ~ 10³ W/cm² at the fibre core. At these intensities, the required exposure time is about 2 mins. It will be appreciated that the argon- ion laser is a poor source of near-UV for mass-manufacture of fibre Bragg ratings because they are very large, extremely inefficient and prone to failure.

There are many design issues to be considered in developing a laser source for these applications. There are several Nd⁺ host crystals that are available, including YAG, YVO₄, GdVO₄, YAIO₃, and YLF. The wavelength of the ⁴F_3Z2 - V³/₂ neodymium ion transition in these hosts range from 1313 ran to 1342 nm, which are all acceptable starting wavelengths. However, YVO₄ is generally the Nd³⁺ host material of choice for laser generation on the 1.3μm transition, the emission cross-section for the 1342 nm transition in Nd:YV0₄ roughly equalling that for the 1064 nm transition in Nd: YAG. The frequency quadrupling of the light from the ⁴FM - ⁴I¹³/₂ transition would provide near UV light. However strong thermal lensing in the laser crystal makes power scaling of diode-end-pumped Nd: YVO₄ lasers difficult, especially so for 1342 nm operation since the relatively high quantum defect and excited state absorption for 1342 nm compared to 1064 nm operation result in greater heat deposition in the pump volume. These thermal lensing problems can be substantially alleviated by using low Nd³⁺ dopant concentrations, in the range 0.25-0.5%, and there have been several recent reports of power-scaling of diode-end-pumped Nd: YVO₄ lasers to ~10W output powers for both the 1064 nm and 1342 nm transitions. Djode-side-pumped Nd: YVO₄ lasers have also achieved high 1064 nm powers for grazing-incidence resonator and master oscillator power amplifier (MOPA) arrangements but the comparatively low gain at 1342 nm necessitates rather complicated multipass techniques to achieve adequate extraction efficiencies from MOPA arrangements.

Unfortunately, Nd:YV0₄ displays a very strong thermal lens when optically pumped. It is particularly strong for the 1342 nm ⁴F₃^ - ⁴Iπ/₂ transition in Nd⁺ because of strong excited state absorption. For example, the focal length of a thermal lens in a Nd: YVO₄ crystal pumped with 18W of 808 nm light was around 80 mm. Along with the severe thermal lensing, the lower emission cross section and significant excited state absorption of the 1342nm transition make short, high peak power pulse generation difficult. It will be appreciated that these issues pose a very difficult problem for the laser engineer attempting to build a near ultraviolet laser.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is a resonator comprising: a pair of spaced apart mirrors one being a convex mirror; and a laser gain medium interposed between the two mirrors and exhibiting a thermal lens.

Preferably the convex mirror has a focal length wherein the resonator is stable at required optical pump powers. .

Preferably the focal length of the convex mirror substantially optimises a resonator beam waist adjacent one of the pair of mirrors being a flat mirror inside the resonator. More preferably the focal length of the convex mirror is designed to match a resonator beam waist to a pump beam waist within the laser gain medium.

Preferably the laser gain medium is a neodymium doped laser crystal. More preferably the laser gain is provided by the ⁴F ^"V₂ - ⁴1¹³/2 transition of the neodymium ion, which provides a fundamental resonator wavelength in the range from 1313 nm to 1342 nm. Still more preferably the laser gain medium is a crystal fabricated of neodymium doped yttrium ortho- vanadate Nd: YVO₄: Even more preferably the laser crystal is adapted to be optically pumped by- the output of a diode laser.

Alternatively, the laser crystal is Nd: YAG.

Alternatively, the laser crystal is Nd:GdVO₄.

Alternatively, the laser crystal is Nd:LuVO₄

Alternatively, the laser crystal is Nd:YAIθ₃-

Alternatively, the laser crystal is Nd: YLF.

Preferably the focal length of the convex mirror is also designed so that there is an extra- resonator laser beam waist minimum near the flat mirror. Preferably the resonator also comprises a second wavelength conversion crystal located outside the resonator at the extra-resonator beam waist minimum. More preferably the second wavelength conversion crystal is fabricated of beta barium borate (BBO).

Preferably the wavelength of a light after the second wavelength conversion crystal has a significant component at substantially 336 nm.

According to yet another aspect of the invention there is provided a solid-state laser including a resonator of either of the preceding aspects of the invention.

According to another aspect of the invention there is provided a resonator comprising: a pair of spaced apart mirrors; and a laser gain medium interposed between the two mirrors and exhibiting a thermal lens.

Preferably the space between the mirrors is chosen so that the resonator is stable at a required optical pump powers, the chosen space between the mirrors substantially optimising the beam waists inside the resonator adjacent one of the pair of mirrors being a flat mirror. More preferably the space between the two mirrors is chosen to match a resonator beam waist to a pump beam waist within the laser gain medium.

Preferably there is a first wavelength conversion crystal located inside the resonator and adjacent the flat mirror. It is understood that this arrangement enables efficient intra- resonator wavelength conversion. More preferably the first wavelength conversion crystal is fabricated of lithium triborate (LBO).

Preferably the resonator output is pulsed at a repetition rate from 100Hz to lOOMHz. More preferably the pulsed output is because of a Q-switch interposed between the two mirrors. Even more preferably the Q-switch is an acousto-optic Q-switch. Alternatively, the Q-switch is a passive Q-switch. Alternatively the pulsed output is because of a mode locking device incorporated as part of the cavity.

According to a further aspect of the invention there is provided a laser beam wavelength conversion device comprising: a first mirror being adapted to pass a laser beam of a first wavelength and being reflective to the laser beam at a second wavelength; a wavelength conversion crystal located adjacent the first mirror and being adapted.to convert a fraction of the laser beam from the first wavelength to a second wavelength; and a second mirror located adjacent the wavelength conversion crystal and being adapted to pass light of the second wavelength but being reflective to light of the first wavelength thereby returning said light through the wavelength conversion crystal for improved wavelength conversion to the second wavelength.

Preferably the wavelength conversion crystal is fabricated of beta barium borate (BBO).

Preferably the first wavelength is substantially 671 nm and the second wavelength is substantially 336 nm.

Preferably the laser beam has a minimum waist diameter near the wavelength conversion crystal-

According to yet a further aspect of the invention there is provided a method of detecting a target element of an associated background material, said method comprising the steps of: attaching a fluorescent label to the target element; and exposing the background material to a light beam from a laser which is designed to. preferentially excite the fluorescent label for detection of the target element.

Preferably the laser is a pulsed laser and the fluorescence decay lifetime of the fluorescent label is long compared with the decay lifetime of an autofluorescence of the background material, detection of the target element being effected by time gated detection of the long lifetime fluorescence from the fluorescent label in preference to the short lifetime fluorescence of the background material. More preferably during this step of gated detection, the fluorescent light detector is open or active only after the background fluorescence and laser pulse have substantially ceased. Even more preferably detection ceases before a subsequent pulse is emitted by the pulsed laser.

Preferably the method also comprises the step of directing the laser beam to provide localised and selective excitation of the background material.Preferably the fluorescent label is a lanthide chelate conjugated to a biochemical substrate. More preferably the fluorescent label is an antibody conjugated lanthanide chelate. Even more preferably the lanthanide is europium,

Preferably the fluorescent label is antibody conjugated europium chelate 4,4 '-bis- (rⁱ ₁l",l ",2",2",3",3"-heptafluro-4",6"-hexanedion-6"-yl)sulfonylamino-propyl-ester-N- succinimide-ester-σ-terphenyl. More preferably this target label is activated to bind to protein via a mild succinimide activation.

Preferably the wavelength of the laser light is substantially within the absorption band of the antibody conjugated lanthanide chelate. More preferably the wavelength of the laser light is substantially within an absorption band of the antibody conjugated europium chelate 4,4'-bis- (l",l'^>,l^<',2",2'',3",3"-heptafluro-4",6''-hexanedion-6'^>-y])sulfonylamino-propyl-ester-N- succinirnide-ester-ø-terphenyl.

Preferably the wavelength of the laser light is substantially 335 nm, being the absorption peak of antibody conjugated europium chelate 4,4'-bis-(rⁱ ₁l",l",2",2",3",3¹'-heptafluro-4",6"- hexanedion-6"-yl)sulfoτιy]amino-propyl-ester-N-succinimide-ester-o-terphenyl.

Preferably the laser pulses have a repetition rate from 100Hz to 100MHz.

According to still a further aspect of the current invention there is provided a method of writing a Bragg grating in an optical waveguide, said method comprising the steps of: providing a frequency quadrupled solid state laser incorporating a neodymium doped laser crystal; illuminating through a holographic phase mask the optical waveguide with the laser for effective writing of the Bragg grating.

Preferably the laser gain is provided by the ⁴F ³/₂ - ⁴1 ¹³/₂ transition of the neodymium ion, which provides a fundamental resonator wavelength in the range from 1313 nm to 1342 nm. More preferably the laser crystal is substantially Νd÷YVCV

Preferably the frequency quadrupling is performed using a first frequency conversion crystal and a second frequency conversion crystal.

Preferably the first frequency conversion crystal is within a resonator of the solid state laser.

Preferably the second frequency conversion crystal is outside the laser resonator. Preferably the laser output is pulsed at a repetition rate from 100Hz to 100MHz. More preferably the pulsed output is because of a Q-switch Within the resonator, Even more preferably the Q-switch is an acousto-optic Q-switch, Alternatively, the Q-switch is a passive Q-switch. Alternatively the pulsed output is because of a mode locking device incorporated as part of the resonator.

According to one aspect of the invention there is provided a method of detecting a target element of an associated background material, said method comprising the steps of: attaching a fluorescent label to the target element; and exposing the background material to a light beam from a pulsed laser of repetition rate greater than 100Hz, the light preferentially exciting the fluorescent label for detection of the target element.

According to another aspect of the invention there is provided a method of detecting a target element of an associated background material, said method comprising the steps of:

, attaching a fluorescent label to the target element; and exposing the background material to a light beam from a laser comprising i) a pair of spaced apart mirrors one being a convex mirror, and ii) a laser gain medium interposed between the two mirrors and exhibiting a thermal lens.

According to still another aspect of the invention there is provided a solid-state laser comprising: . a pair of spaced apart mirrors defining a resonator, one mirror being a convex mirror; a gain medium interposed between the two mirrors and exhibiting a thermal lens; and a laser diode operatively coupled to the gain medium.

According to still another aspect of the invention there is provided a resonator comprising: a pair of spaced apart flat mirrors; and a laser gain medium interposed between the two mirrors and exhibiting a thermal lens.

Compact, efficient laser sources emitting in the low-end (320-340nm) of the UV-A spectral band can be expected to find wide application in time resolved fluorescence detection including laser scanning cytometry, time resolved flow cytometry. Practical, high repetition rate (1Os-IOOs kHz) pulse lasers of moderate power (10s mW) operating at wavelengths around 335 nm for excitation of lanthide chelate fluorescent probes are required. These same sources will also prove to be exceptional for the writing of fibre Bragg gratings, creating structures using stereo lithography and mass spectroscopy.

BRIEF DESCRIPTION OF THE FIGURES

In order to achieve a better understanding of the nature of the present invention a preferred embodiment of a resonator, a solid state laser, a laser beam wavelength conversion device, and a method of detecting target elements of an associated background material together with a method of writing a Bragg grating in a wavelength will now be described, by way of example only, with reference to the accompanying drawings in which:

Figure 1 shows a schematic illustration of a resonator and a solid state laser of an embodiment of one aspect of the invention.;

Figure 2 graphically depicts the influence of resonator end mirror curvature variation on laser mode sizes for a (a) resonator with flat end mirrors, (b) resonator with one flat end mirror and another end mirror with radius of curvature 500 mm, (c) resonator with one flat end mirror and another end mirror with radius of curvature 250 mm.

Figure 3 shows a schematic illustration of a laser beam wavelength conversion device of an embodiment of another aspect of the invention.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT OF THE INVENTION

In one embodiment of one aspect of the invention as shown in figure 1, there is provided a solid state laser designated generally as 10. The laser 10 includes a resonator 15 having an elongate cavity together with a substantially flat mirror 20 located at one end of the resonator 15. The flat mirror 20 in this embodiment is highly reflective at a wavelength of 1342 nm and highly transmittivc at a wavelength of 1064 nm. The laser 10 also includes a convex mirror 30 located at an opposite end of the resonator 15. In this embodiment the convex mirror 30 is highly reflective at 1342 nm, highly transmittive at 1064 nm, and substantially transmittive at 808 nm. In this embodiment the radius of curvature of the convex end mirror 30 is in the range of ∞ to 100 mm but preferably around 500 mm. These focal lengths will vary depending on the maximum available pump power. The mirrors 20 to 30 are separated by between 120 mm to 140 mm but preferably 120 mm. It is understood that these valves may be increased in order to fit components of a different size inside the resonator 15,

The resonator 15 further includes a laser gain medium 40 located adjacent the convex mirror 30, and exhibiting a thermal lens when optically pumped. In this embodiment the laser gain medium 40 is a laser crystal of neodymium orthovanadate (Nd: YVO₄), with 0.3 atomic percent of neodymium. The laser crystal 40 has dimensions of approximately 3x3x12 mm and has antireflective coatings for wavelengths of between 800-1342 nm on both end faces. The laser crystal 40 is mounted in a temperature controlled copper mount and held in place using 100 micrometer thick indium foil. In this embodiment the light 50 from a 20 Watt fibre coupled diode 60, of emission wavelength 80S mm, is collimated and reimaged through the convex mirror 30, using convex lenses 70 and 80, to a waist radius of about 300 micrometers inside the laser crystal 40. It will be appreciated that this pumping geometry results in a laser of a simple and compact design.

The laser crystal 40 exhibits a thermal lens when optically pumped. In this embodiment the focal length of the thermal lens is between ∞ and 80 mm and changes with pump power. Importantly, a focal length of the convex mirror 30 is designed so that the resonator 15 is unstable at relatively low optical pump powers but which becomes stable as the thermal lens increases at high optical pump powers. It will be appreciated that the careful design of the resonator 15 ensures resonator stability. The convex mirror 30 also provides an extra-cavity beam waist minimum.

It is understood that the focal length of the convex mirror 30 substantially optimises the intra- cavity beam waste adjacent the mirrors 20 and 30. The focal length of the convex mirror 30 is designed to match the intra-resonator beam waist to the pump beam waist within the laser gain medium 40. The embodiment described above will provide 1342 nm fundamental laser radiation within the laser resonator 15.

The laser 10 also comprises a first wavelength conversion crystal 90 located inside the resonator 15 and adjacent the flat mirror 20. In this embodiment the conversion crystal 90 is a 15 mm long lithium triborate (LBO) crystal. The LBO crystal is type I critically phase matched for second harmonic generation at 1342 nm (theta = 85.4°, phi = 0°), and held in a thermoelectric temperature controlled copper mount positioned close to the flat or output U

coupling mirror 20. It is understood that this arrangement enables efficient intra-resonator wavelength conversion providing 671 nm radiation 100 from the laser 10.

The laser 10 further comprises a laser Q-switch 110 located between the laser crystal and the conversion crystal. In this embodiment the Q-switch 110 is a 20 Watt acousto-optic Q-switch that is antireflection coated for the wavelength 1342 nm, positioned substantially at the centre of the resonator 15. It is understood that Q-switched operation increases the peak optical power circulating within the resonator 15 thus improving the wavelength conversion " efficiency. The laser 10 additionally comprises a second wavelength conversion crystal, located outside the cavity and preferably at the smallest extra-cavity beam waist possible. In^' this embodiment the second crystal is fabricated from beta barium borate (BBO).

Modelling- of the laser resonator 15 has been undertaken. Cavity mode sizes (radii) at the laser and LBO crystals were calculated for a range of focal lengths for the thermal lens in the laser crystal and are shown in figure 2a for a 120 mm-long flat-flat resonator, in figure 2b for the 120 mm-long convex-flat resonator of figure 1 (50 cm convex), and in figure 2c for the 120 mm long convex-flat resonator of figure 1 (25 cm convex).

The focal length of the thermal lens has in this embodiment been determined experimentally to be close to 80 mm at a maximum pump power incident on the crystal of 18 W. This is illustrated in figure 2a where the cavity mode radius at the laser crystal is seen to blow up at f= ~ 80 mm for the 120 mm-long flat-flat resonator 15 corresponding to the onset of cavity instability at maximum pump power.

The substitution of the convex (r=500 mm) mirror for the flat end mirror introduces a small degree of compensation for the thermal lens in the laser crystal so that for maximum pump power, the resonator 15 remains stable, mode-matching at the gain region is optimized, and a small beam radius (145 μm) is provided at the intracavity LBO frequency-doubler, as illustrated in figure 2b. But the substitution of the convex (r=250 mm) mirror for the flat end mirror introduces too much compensation and the mode matching is no longer ideal, as shown in figure 2c. thus, the curvature of the end mirror must be carefully chosen.

The calculations also show that cavity mode size at both the laser crystal and the intracavity LBO doubler varies comparatively rapidly with increasing thermal lens focal length (decreasing pump power) for the convex-flat resonator. It follows that the convex-flat resonator requires higher pump power to reach laser threshold and delivers lower efficiency at low pump powers due to poorer mode-matching in the gain region compared with the flat-flat resonator 15, but gives significantly better performance at maximum pump power.

Results of calculations for the mode radius of the output beam at the BBO doubler are included in figures 2. It is also noteworthy that the divergence of the output beam is slightly smaller for the convex-flat resonator 15, which is advantageous for frequency conversion in BBO (which has a comparatively small angular acceptance of 0.52 mrad° cm for the 671 to 336 nm type I interaction).

In one embodiment of another aspect of the invention as shown in figure 3, there is provided a laser beam wavelength conversion device 200. This conversion device may be used in conjunction with the solid-state laser 10 of the preceding aspect, instead of the single second wavelength conversion crystal. In this embodiment, enhanced conversion efficiency is obtained using a double pass geometry in which a first flat mirror 210 is highly transmitting (about 96%) at 671 nm and highly reflecting (about 99%) at 336 nm, and a second flat mirror 220 is highly transmitting (about 91%) at 336 nm and highly reflecting (about 99%) at 671 nm. The first 210 and second 220 mirrors are spaced apart with a wavelength conversion crystal 230 in the form of a beta barium borate crystal located therebetween. The second flat mirror 220 transmits forward going 336 nm second harmonic and reflects residual 671 nm back through the beta barium borate crystal 230 for a second pass through the first flat mirror 210 reflecting the backward going 336 nm second harmonic beam into the forward direction throughs the second flat mirror 220. The conversion crystal 230 in this embodiment, is located outside the cavity of the described embodiment of the solid state laser 10 at the extra- cavity beam waist minimum.

According to a further aspect of the invention there is provided a method of detecting target elements of an associated background material. In this embodiment the target. elements are giardiacysts and the background material is a matrix of autofluorescent algae. However, it is to be understood that the target could be any biological material and the matrix (or background material) could be any material.

In this example a fluorescent label attaches to the target element. In this embodiment the label is antibody conjugated europium chelate 4,4MDis-(l V ^1^2^2^3^3"-heptafluro-4'',6''- hexanedϊon-6''-yl)sulfonylamino-propyl-ester-Λ^-succinirnide-ester-o-terphenyl. More preferably this label is activated to bind to protein via a mild succinimide activation. It is understood that the use of this chemical is highly desirable because it has a very long fluorescent lifetime and strong fluorescent intensity compared to other fluorescent labels. It also has a Jong half-life of around six months, which is substantially longer than that of other fluorescent labels. However, the fluorescent label could be a lanthanide chelate conjugated to any biochemical substrate, including antibodies, proteins and nucleotides. The method also involves providing light from a laser which is designed to preferentially excite the fluorescent label for detection of the target element. In this embodiment the light is the frequency quadrupled light from a neodymium orthovanadate Q-switched laser.

The laser is preferably a pulsed laser and the fluroscence lifetime of the fluorescent label is long compared with the decay lifetime of the autofluorescence of the background material. Detection of the target elements is effected by time gated detection of the long lifetime fluorescence from the fluorescent label in preference to the short lifetime fluorescence of the background material. In this embodiment where the pulses are provided from the Q-switched laser the decay lifetime of the autofluorescent background material is of the order of 10 nanoseconds and the lifetime of the fluorescent label is of the order of 100 microseconds or longer. The gated detection is in this example provided by an electron multiplying array detector.

The method of detection also comprises directing the laser beam to provide localised and selective excitation of the background material. The light is directed to a point within the material by fixed optics and microscopes but it is also understood that the optics can be moved to move the point of localised and selective excitation of the background material. It is also understood that the same localised and selective excitation can be obtained by moving the background material.

Preferably the wavelength of the laser light is substantially within the absorption band of the antibody conjugated europium chelate 4,4'-bis-(r',l",l",2"_!2",3",3"-heptafluro-4",6"- hexanedion-6"-yl)sulfonylamino-propyl-ester-N-succinimide-ester-σ-teφhenyl. The wavelength of the laser light is substantially within the absorption of antibody conjugated europium chelate 4_t4'-bis-(l",l",l",2",2",3",3"-heptafluro-4",6"-hexanedion-6"- yOsulfonylamino-propyl-ester-N-succinimide-ester-o-terphenyl, and in this example, the wavelength of the laser light is optimal-close to 335 nm, the absorption peak of antibody conjugated europium chelate 4,4'-bis-(rM:M",2",2",3"₎3"-heptafluro-4"₎6"-hexanedion-6"- y])su]fony]amino-propyl-ester-N-succinimide-ester-σ-terpheny]. In this embodiment the wavelength of the laser light is 336 nm. The laser pulses preferably have a repetition rate from IkHz to 20OkHz and in this embodiment the laser pulses have a repetition rate from 20 kHz to 140 kHz .

In one embodiment of another aspect of the invention there is provided a method of writing a Bragg grating in an optical waveguide. The light from a frequency quadrupled Nd--YVO₄ laser, running at a fundamental frequency of 1342 nm illuminates the optical waveguide after travelling through a holographic phase mask. The frequency conversion is performed firstly by a LBO crystal within the laser resonator and secondly by a BBO crystal external to the laser resonator. The laser is Q-switched acousto-optically to increase the peak optical powers, and thus improve frequency conversion.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. For example, the laser material could be any πeodymium doped laser crystal, and the frequency conversion crystals could be replaced by equivalents. Also, the optical end-pumping of the laser crystal could be replaced by an optical side pumping scheme. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

It is to be understood that any acknowledgement of prior art in this specification is not to be taken as an admission that this prior art forms part of the common general knowledge in Australia or elsewhere.

Claims

16CLAIMS

1. A resonator comprising: a pair of spaced apart mirrors one being a convex mirror; and a laser gain medium interposed between the two mirrors and exhibiting a- thermal lens.

2. A resonator as claimed in claim J wherein the convex mirror has a focal length wherein the resonator is stable at required optical pump powers.

3. A resonator as claimed in claim 2 wherein the focal length of the convex mirror substantially optimises a resonator beam waist adjacent one of the pair of mirrors being a flat mirror inside the resonator.

4. A resonator as claimed in claim 3 wherein the focal length of the convex mirror is designed to match a resonator beam waist to a pump beam waist within the laser gain medium.

5. A resonator as claimed in any one of the preceding claims wherein the laser gain medium is a neodymium doped laser crystal.

6. A resonator as claimed in claim 5 wherein the laser gain is provided by the ⁴F ³/₂ - ⁴I ¹³/₂ transition of the neodymium ion, which provides a fundamental resonator wavelength in the range from 1313 nm to 1342 nm.

7. A resonator as claimed in either of claims 5 or 6 wherein the laser gain medium is a crystal fabricated of neodymium doped yttrium ortho-vanadate (Nd:YVO₄).

8. A resonator as claimed in any one of the preceding claims wherein the laser crystal is adapted to be optically pumped by the output of a diode laser.

9. A resonator as claimed in claim 5 wherein the laser crystal is Nd: YAG.

10. A resonator as claimed in claim 5 wherein the laser crystal is Nd:GdVO₄.

11. A resonator as claimed in claim 5 wherein the laser crystal is Nd:LuVO₄

12. A resonator as claimed in claim 5 wherein the laser crystal is Nd:YAIO₃. 1 /

13. A resonator as claimed in claim 5 wherein the laser crystal is Nd: YLF.

14. A resonator as claimed in either of claims 3 or 4 wherein the focal length of the convex mirror is also designed so that there is an extra-resonator laser beam waist minimum near the flat mirror.

15. A resonator as claimed in either of claims 3 or 4 also comprising a first wavelength conversion crystal located inside the resonator and adjacent the flat mirror.

16. A resonator as defined in claim 15 wherein the first wavelength conversion crystal is fabricated of lithium triborate (LBO).

17. A resonator as claimed in any one of claims 14 to 16 also comprising a second wavelength conversion crystal located outside the resonator at the extra-resonator laser beam waist minimum. .

18. A resonator as claimed in claim 17 wherein the second wavelength conversion crystal is fabricated of beta barium borate (BBO).

19. A resonator as claimed in claim 18 wherein the wavelength of a light after the second wavelength conversion crystal has a significant component at substantially 336 nm.

20. A resonator comprising: a pair of spaced apart mirrors; and a laser gain medium interposed between the two mirrors and exhibiting a thermal lens.

21. A resonator as claimed in claim 20 wherein the space between the mirrors is chosen so that the resonator is stable at a required optical pump powers, the chosen space between the mirrors substantially optimising the beam waists inside the resonator adjacent one of the pair of mirrors being a flat mirror.

22. A resonator as claimed in claim 21 wherein the space between the two mirrors is chosen to match a resonator beam waist to a pump beam waist within the laser gain medium. 18

23. A resonator as claimed in either of claims 21 or 22 also comprising a first wavelength conversion crystal located inside the resonator and adjacent the flat mirror.

24, A resonator as claimed in claim 23 wherein the first wavelength conversion crystal is fabricated of lithium triborate (LBO).

25. A resonator as claimed in any one of the preceding claims wherein a resonator output is pulsed at a repetition rate from 100Hz to 100MHz.

26. A resonator as claimed in claim 25 wherein the pulsed output is because of a Q-switch interposed between the two mirrors.

27. A resonator as claimed in claim 26 wherein the Q-switch is an acousto-optic Q-switch.

28. A resonator as claimed in claim 26 wherein the Q-switch is a passive Q-switch.

' 29. A resonator as claimed in claim 25 wherein the pulsed output is because of a mode locking device incorporated as part of the resonator.

30. A laser beam wavelength conversion device comprising: a first mirror being adapted to pass a laser beam of a first wavelength and being reflective to the laser beam at a second wavelength; a wavelength conversion crystal located adjacent the first mirror and being adapted to convert a fraction of the laser beam from the first wavelength to a second wavelength; and a second mirror located adjacent^' the wavelength conversion crystal and being adapted to pass light of the second wavelength but being reflective to light of the first wavelength thereby returning said light through the wavelength conversion crystal for improved wavelength conversion to the second wavelength.

31. ^" A laser beam wavelength conversion device as claimed in claim 30 wherein the wavelength conversion crystal is fabricated of beta barium borate (BBO).

32. A laser beam wavelength conversion device as claimed in either of claims 30 or 31 wherein the first wavelength is substantially 671 nm and the second wavelength is substantially 336 nm. 19

33. A laser beam wavelength conversion device as claimed in any one of claims 30 to 32 wherein the laser beam has a minimum waist diameter near the wavelength conversion crystal.

34. A method of detecting a target element of an associated background material, said method comprising the steps of: attaching a fluorescent label to the target element; and exposing the background material to a light beam from a laser which is designed to preferentially excite the fluorescent label for detection of the target element.

35, A method as claimed in claim 34 wherein the laser is a pulsed laser and the fluorescence decay lifetime of the fluorescent label is long compared with the decay lifetime of an autofluorescence of the background material, detection of the target element being effected by time gated detection of the long lifetime fluorescence from the fluorescent label in preference to the short lifetime fluorescence of the background material.

36. A method as claimed in claim 35 wherein during the step of gated detection, the fluorescent light detector is open or active only after the background fluorescence and laser pulse have substantially ceased.

37. A method as claimed in claim 36 wherein detection ceases before a subsequent pulse is emitted by the pulsed laser.

38. A method as claimed in any one of claims 34 to 37 also comprising the step of directing the light beam to provide localised and selective excitation of the background material.

39. A method as claimed in any one of claims 34 to 38 wherein the fluorescent label is a lanthanide chelate conjugated to a biochemical substrate.

40. A method as claimed in any one of claims 34 to 39 wherein the fluorescent label is an antibody conjugated lanthanide chelate.

41. A method as claimed in claim 40 wherein the lanthanide is europium. 20

42. A method as claimed in claim 39 wherein the fluorescent label is antibody conjugated europium chelate 4,4'-bis-(l",l",l",2",2",3",3"-heptaflυro-4"₎6"-hexanedion-6"- yOsulfonylamino-propyl-ester-N-succinimide-ester-c-terphenyl.

43. A method as claimed in claim 42 wherein the fluorescent label is activated to bind to a protein via a mild succinimide activation.

44. A method as claimed in either of claims 40 or 41 wherein the wavelength of the light beam is substantially within the absorption band of the antibody conjugated lanthanide chelate.

45. A method as claimed in either of claims 42 or 43 wherein the wavelength of the laser light is substantially within an absorption band of the antibody conjugated europium chelate 4,4'-bis-(l",l",l",2",2",3",3"-heptafluro-4",6"-hexanedioii-6"- yl)sulfonylamino-propyl-ester-N-succinimide-ester-σ-terphenyl.

46. A method as claimed in either of claims 42 or 43 wherein the wavelength of the laser light is substantially 335 nm, being the absorption peak of antibody conjugated europium chelate 4₎4'-bis-(r^l,rM",2",2",3",3"-heptafluro-4"_t6"-hexanedion-6"- yl)sulfonylamino-proρyl-ester-N-succinimide-ester-o-terphenyl.

47. A method of detecting a target element of an associated background material, said method comprising the steps of: attaching a fluorescent label to the target element; and exposing the background material to a light beam from a pulsed laser of repetition rate greater than 100Hz, the light preferentially exciting the fluorescent label for detection of the target element.-

48. A method of detecting a target element of an associated background material, said ^■ method comprising the steps of: attaching a fluorescent label to the target element; and exposing the background material to a light beam from a laser comprising i) a pair of spaced apart mirrors one being a convex mirror, and ii) a laser gain medium interposed between the two mirrors and exhibiting a thermal lens. 21

49. A method of writing a Bragg grating in an optical waveguide, said method comprising the steps of: providing a frequency quadrupled solid state laser incorporating a neodymium doped laser crystal; illuminating through a holographic phase mask the optical waveguide with the laser for effective writing of the Bragg grating.

50. A method of writing a Bragg grating as claimed in claim 49 wherein the laser gain is provided by the ⁴F ³/₂ - ⁴1 ¹³/₂ transition of the neodymium ion, which provides a fundamental resonator wavelength in the range from 1313 ran to 1342 run.

51. A method of writing a Bragg grating as claimed in claim 50 wherein the laser crystal is substantially Nd; YYO₄.

52. A method of writing a Bragg grating as claimed in any one of claims 49 to 51 wherein a First frequency conversion crystal is within a resonator of the solid state laser.

53. A method of writing a Bragg grating as claimed in claim 52 wherein a second frequency conversion crystal is outside of the laser resonator.

54. A method of writing a Bragg grating as claimed in either of claims 52 or 53 wherein the laser output is pulsed at a repetition rate from 100Hz to 100MHz.

55. A method of writing a Bragg grating as claimed in claim 54 wherein the pulsed output is because of a Q-switch within the laser resonator.

56. A method of writing a Bragg grating as claimed in claim 55 wherein the Q-switch is an acousto-optic Q-switch.

57. A method of writing a Bragg grating as claimed in claim 55 wherein the Q-switch is a passive Q-switch.

58. A method of writing a Bragg grating as claimed in claim 54 wherein the pulsed output is because of a mode locking device incorporated as part of the resonator.

59. A resonator comprising: a pair of spaced apart flat mirrors; and 22

a laser gain medium interposed between the two mirrors and exhibiting a thermal lens.

60. A solid-state laser comprising: a pair of spaced apart mirrors defining a resonator, one mirror being a convex mirror; a gain medium interposed between the two mirrors and exhibiting a thermal lens; and a laser diode operative! y coupled to the gain medium.