Removable tip for laser device

Abstract

The present invention provides an improved method of measuring analytes in bodily fluids without the use of a sharp. The method having the steps of irradiating the skin of a patient by focused pulses of electromagnetic energy emitted by a laser. By proper selection of wavelength, energy fluence, pulse temporal width and irradiation spot size, the pulses precisely irradiate the skin to a selectable depth, without causing clinically relevant damage to healthy portions of the skin. After irradiation, interstitial fluid is collected into a container or left on the skin. The interstitial fluid is then tested for a desired analyte to approximate the analyte concentration in other bodily fluids. Alternatively, after the forced formation of a microblister, the epidermis covering the microblister is lysed and the interstitial fluid is subsequently collected and tested.

We claim:  
     
         1 . A method of measuring analyte concentrations in bodily fluids, comprising the steps of: 
 a) focusing a laser beam with sufficient energy fluence to ablate the skin at least as deep as the stratum corneum, but not as deep as the capillary layer;    b) firing the laser to create a site of ablation, the site having a diameter of between 0.5 microns and 5.0 cm;    c) collecting a sample of interstitial fluid released by steps (a) and (b); and    d) testing the interstitial fluid for analyte concentration.    
     
     
         2 . The method of  claim 1  wherein the laser beam has a wavelength of 0.2-10 microns.  
     
     
         3 . The method of  claim 1  wherein the laser beam has a wavelength of between 1.5-3.0 microns.  
     
     
         4 . The method of  claim 1  wherein the laser beam has a wavelength of about 2.94 microns.  
     
     
         5 . The method of  claim 1  wherein the laser beam is emitted by a laser selected from the group consisting of Er: YAG, pulsed CO 2 , Ho:YAG, Er:YAP, Er/Cr:YSGG, Ho:YSGG, Er:GGSG, Er:YLF, Tm:YAG, Ho:YAG, Ho/Nd:Yalo 3 , cobalt:MgF 2 , HF chemical, DF chemical, carbon monoxide, deep UV lasers, and frequency tripled Nd:YAG lasers.  
     
     
         6 . The method of  claim 1  wherein the laser beam is emitted by an Er:YAG laser.  
     
     
         7 . The method of  claim 1  wherein the laser beam-is emitted by a modulated laser selected from the group consisting of continuous-wave CO 2 , Nd:YAG, Thallium:YAG and diode lasers.  
     
     
         8 . The method of  claim 1  wherein the laser beam is focused at a site on the skin with a diameter of 0.1-5.0 mm.  
     
     
         9 . The method of  claim 1  wherein the energy fluence of the laser beam at the skin is 0.03-100,000 J/cm 2 .  
     
     
         10 . The method of  claim 1  wherein the energy fluence of the laser beam at the skin is 0.03-9.6 J/cm 2 .  
     
     
         11 . The method of  claim 1  wherein multiple ablations are made to prepare the skin for diffusion of interstitial fluid.  
     
     
         12 . The method of  claim 1  wherein multiple ablations are made to prepare the skin for pharmaceutical delivery.  
     
     
         13 . The method of  claim 1  further comprising a beam splitter positioned to create, simultaneously from the laser, multiple sites of ablation.  
     
     
         14 . The method of  claim 13  wherein the beam splitter is selected from a series of partially silvered mirrors, a series of dichroic mirrors, and a series of beam-splitting prisms.  
     
     
         15 . The method of  claim 1  further comprising an acousto-optic modulator outside the laser cavity wherein the modulator consecutively deflects the beam at different angles to create different sites of ablation on the skin.  
     
     
         16 . The method of  claim 1  wherein the analyte to be measured is selected from the group consisting of Na + , K + , Ca ++ , Mg ++ , Cl − , HCO 3   − , HHCO 3 , phosphates, S 4   − , glucose, amino acid, cholesterol, phospholipids, neutral fat, PO 2   − , pH, organic acids or proteins.  
     
     
         17 . The method of  claim 1  wherein the analyte measurement is used to represent the analyte concentration in blood.  
     
     
         18 . The method of  claim 1  wherein the interstitial fluid is collected in a container positioned proximal to the ablation site and through which the laser beam passes.  
     
     
         19 . The method of  claim 18  wherein the testing of analyte concentration is conducted while the container unit is attached to the laser device.  
     
     
         20 . The method of  claim 1  further comprising the step of applying a therapeutically effective amount of a pharmaceutical composition at the site of ablation.  
     
     
         21 . The method of  claim 20  wherein the pharmaceutical substance is administered based on analyte concentration in the interstitial fluid.  
     
     
         22 . The method of  claim 1  further comprising the step of applying a pressure gradient to the skin after formation of the site of ablation to increase the diffusion rate of interstitial fluid.  
     
     
         23 . The method of  claim 1  further comprising the step of mechanically increasing the diffusion rate of interstitial fluid after formation of a site of ablation.  
     
     
         24 . The method of  claim 23  wherein diffusion is increased by the application of subatmospheric pressure at the ablation site.  
     
     
         25 . The method of  claim 24  wherein the container unit is under subatmospheric pressure  
     
     
         26 . The method of  claim 1  wherein a pressure gradient is created at the site of ablation to increase the removal of bodily fluids.  
     
     
         27 . A method of measuring analyte concentrations in bodily fluids, comprising the steps of: 
 a) focusing a laser beam with sufficient energy fluence to alter the skin at least as deep as the stratum corneum, but not as deep as the capillary layer; and    b) firing the laser to create a site of alteration, the site having a diameter of between 0.5 microns and 5.0 cm.    c) collecting a sample of interstitial fluid released by steps (a) and (b); and    d) testing the fluid for analyte concentration.    
     
     
         28 . The method of  claim 27  wherein the laser beam has a wavelength of 0.2-10 microns.  
     
     
         29 . The method of  claim 27  wherein the laser beam has a wavelength of between 1.5-3.0 microns.  
     
     
         30 . The method of  claim 27  wherein the laser beam has a wavelength of about 2.94 microns.  
     
     
         31 . The method of  claim 27  wherein the laser beam is emitted by a laser selected from the group consisting of Er:YAG, pulsed CO 2 , Ho:YAG, Er:YAP, Er/Cr:YSGG, Ho:YSGG, Er:GGSG, Er:YLF, Tm:YAG, Ho:YAG, Ho/Nd:Yalo 3 , cobalt:MgF 2 , HF chemical, DF chemical, carbon monoxide, deep UV lasers, and frequency tripled Nd:YAG lasers.  
     
     
         32 . The method of  claim 27  wherein the laser beam is emitted by an Er:YAG laser.  
     
     
         33 . The method of  claim 27  wherein the laser beam is emitted by a modulated laser selected from the group consisting of continuous-wave CO 2 , Nd:YAG, Thallium:YAG and diode lasers.  
     
     
         34 . The method of  claim 27  wherein the laser beam is focused at a site on the skin with a diameter of 0.1-5.0 mm.  
     
     
         35 . The method of  claim 27  wherein the energy fluence of the laser beam at the skin is 0.03-100,000 J/cm 2   
     
     
         36 . The method of  claim 27  wherein the energy fluence of the laser beam at the skin is 0.03-9.6 J/cm 2 .  
     
     
         37 . The method of  claim 27  wherein multiple alterations are made to prepare the skin for diffusion of interstitial fluid.  
     
     
         38 . The method of  claim 27  wherein multiple alterations are made to prepare the skin for pharmaceutical delivery.  
     
     
         39 . The method of  claim 27  further comprising a beam splitter positioned to create, simultaneously from the laser, multiple sites of alteration.  
     
     
         40 . The method of  claim 39  wherein the beam splitter is selected from a series of partially silvered mirrors, a series of dichroic mirrors, and a series of beam-splitting prisms.  
     
     
         41 . The method of  claim 27  further comprising an acousto-optic modulator outside the laser cavity wherein the modulator consecutively deflects the beam at different angles to create different sites of alteration on the skin.  
     
     
         42 . The method of  claim 27  wherein the analyte to be measured is selected from the group consisting of Na + , K + , Ca ++ , Mg ++ , Cl − , HCO 3   − , HHCO 3 , phosphates, S 4   − , glucose, amino acid, cholesterol, phospholipids, neutral fat, PO 2   − , pH, organic acids or proteins.  
     
     
         43 . The method of  claim 27  wherein the analyte measurement is used to represent the analyte concentration in blood.  
     
     
         44 . The method of  claim 27  wherein the interstitial fluid is collected in a container positioned proximal to the ablation site and through which the laser beam passes.  
     
     
         45 . The method of  claim 27  wherein the testing of analyte concentration is conducted while the container unit is attached to the laser device.  
     
     
         46 . The method of  claim 27  further comprising the step of applying a therapeutically effective amount of a pharmaceutical composition at the site of alteration.  
     
     
         47 . The method of  claim 46  wherein the pharmaceutical substance is administered based on analyte concentration in the interstitial fluids.  
     
     
         48 . The method of  claim 27  further comprising the step of applying a pressure gradient to the skin after formation of the site of ablation to increase the diffusion rate of interstitial fluid.  
     
     
         49 . The method of  claim 27  further comprising the step of mechanically increasing the diffusion rate of interstitial fluid after formation of a site of alteration.  
     
     
         50 . The method of  claim 49  wherein diffusion is increased by the application of sub-atmospheric pressure at the alteration site.  
     
     
         51 . The method of  claim 50  wherein the container unit is under sub-atmospheric pressure.  
     
     
         52 . The method of  claim 27  wherein a pressure gradient is created at the site of alteration to increase the removal of bodily fluids.  
     
     
         53 . A method of measuring analyte concentration in bodily fluids, comprising the steps of: 
 a) applying sub-atmospheric pressure at the surface of the skin to induce the formation of a microblister;    b) focusing a laser beam with sufficient energy fluence to lyse a microblister;    c) firing the laser to lyse the blister;    d) collecting a sample of interstitial fluid released by steps (a), (b) and (c); and    e) testing the fluid for analyte concentration.    
     
     
         54 . The method of  claim 53  wherein the laser beam has a wavelength of 0.2-10 microns.  
     
     
         55 . The method of  claim 53  wherein the laser beam has a wavelength of between 1.5-3.0 microns.  
     
     
         56 . The method of  claim 53  wherein the laser beam has a wavelength of about 2.94 microns.  
     
     
         57 . The method of  claim 53  wherein the laser beam is emitted by a laser selected from the group consisting of Er:YAG, pulsed CO 2  Ho:YAG, Er:YAP, Er/Cr:YSGG, Ho:YSGG, Er:GGSG, Er:YLF, Tm:YAG, Ho:YAG, Ho/Nd:Yalo 3 , cobalt:MgF 2 , HF chemical, DF chemical, carbon monoxide, deep UV lasers, and frequency tripled Nd:YAG lasers.  
     
     
         58 . The method of  claim 53  wherein the laser beam is emitted by an Er:YAG laser.  
     
     
         59 . The method of  claim 53  wherein the laser beam is emitted by a modulated laser selected from the group consisting of continuous-wave CO 2 , Nd:YAG, Thallium:YAG and diode lasers.  
     
     
         60 . The method of  claim 53  wherein the laser beam is focused at a site on the skin with a diameter of 0.1-5.0 mm.  
     
     
         61 . The method of  claim 53  wherein the energy fluence of the laser beam at the skin is 0.03-100,000 J/cm 2 .  
     
     
         62 . The method of  claim 53  wherein the energy fluence of the laser beam at the skin is 0.03-9.6 J/cm 2 .  
     
     
         63 . The method of  claim 53  wherein multiple microblisters are made for collection of interstitial fluid.  
     
     
         64 . The method of  claim 53  further comprising a beam splitter positioned to lyse, simultaneously from the laser, multiple microblisters.  
     
     
         65 . The method of  claim 64  wherein the beam splitter is selected from a series of partially silvered mirrors, a series of dichroic mirrors, and a series of beam-splitting prisms.  
     
     
         66 . The method of  claim 53  further comprising an acousto-optic modulator outside the laser cavity wherein the modulator consecutively deflects the beam at different angles to lyse different microblisters.  
     
     
         67 . The method of  claim 53  wherein the analyte to be measured is selected from the group consisting of Na + , K + , Ca ++ , Mg ++ , Cl − , HCO 3   − , HHCO 3   − , phosphates, S 4   − , glucose, amino acid, cholesterol, phospholipids, neutral fat, PO 2   − , pH, organic acids or proteins.  
     
     
         68 . The method of  claim 53  wherein the analyte measurement is used to represent the analyte concentration in blood.  
     
     
         69 . The method of  claim 53  wherein the interstitial fluid is collected in a container positioned proximal to the microblister and through which the laser beam passes.  
     
     
         70 . The method of  claim 53  wherein the testing of analyte concentration is conducted while the container unit is attached to the laser device.  
     
     
         71 . The method of  claim 53  further comprising the step of applying a therapeutically effective amount of a pharmaceutical composition at the site of the lysed microblister.  
     
     
         72 . The method of claim  71  wherein the pharmaceutical substance is administered based on analyte concentration in the interstitial fluid.