« PreviousContinue »
FIELD OF THE INVENTION
This invention relates broadly to sterilization of medical devices by ultraviolet radiation. More specifically, this invention relates to a sterilization system by which the amount of radiation produced by the sterilization system is measured, and to the method of measuring and controlling the amount of radiation produced by the sterilization system.
DESCRIPTION OF THE RELATED ART
Medical device sterilization processes and in particular commercial contact lens manufacturing sterilization processes typically involve some form of temperature and/or pressure-based sterilization techniques. For example, a hydrophilic contact lens is typically first formed by injecting a monomer mixture into a mold. The monomer mixture is then polymerized (i.e. the lenses are cured). After other optional processing steps, such as quality inspections, the lens is placed in a container with a solution and the container is sealed. The packaged lens is sterilized by placing the container in an autoclave at an elevated humidity, temperature and pressure for an extended period of time, usually at least 15 minutes, and more typically 30 minutes. Although this commercial process produces thoroughly sterilized contact lenses, the batch-wise autoclave sterilization step is time consuming, costly, and inefficient.
European Patent Application No. 0 222 309 Al discloses a process using ozone, in which packaging material is disinfected in a manufacturing setting. The process involves feeding an oxygen stream into an ozonating chamber, generating ozone from oxygen in the ozonating chamber, placing packaging containers in a sanitizing chamber, feeding the ozone into the sanitizing chamber, and purging the ozone from the sanitizing chamber with sterile air. The process requires that the ozone contact the packaging material for a predetermined time, followed by the sterile air purge step. The process is offered as an alternative to heat-steam sterilization, sterilization by application of electromagnetic radiation, or chemical agent sterilization.
U.S. Pat. No. 5,618,492 discloses a process for producing a sterile contact lens in a sealed container during a continuous production process wherein the contact lens is immersed in an ozone-containing solution within a container during a continuous lens packaging process, and the lens and container are subsequently subjected to ultraviolet radiation primarily to degrade the ozone. This process sterilizes the contact lens and the container.
U.S. Pat. No. 4,464,336 teaches a method of sterilization using a flash discharge ultraviolet lamp, which produces a very large instantaneous output, which is capable of deactivating microorganisms, including Aspergillus niger.
U.S. Pat. Nos. 5,034,235 and 4,871,559 disclose the use of intermittent pulses of very intense, very short duration pulses of light in the visible and near visible frequencies to inactivate microorganisms on the surface of food products, and suggest that the method can be used for packages, medical devices, and food products in packages.
U.S Pat. No. 5,786,598 discloses the idea of using a flash lamp system to sterilize contact lenses in a preserved solution in a container, however, there are no conditions defined to accomplish sterility, nor examples which show that sterility can be accomplished.
U.S. Pat. No. 4,629,896 discloses an apparatus for monitoring the intensity of a UV source (for example, a water
sterilizer) in which there is an optical detection unit which detects uv radiation and converts that radiation into an electrical signal, so that the intensity of the radiation can be monitored, and when it falls below a certain level the lamp
5 can be shut off.
WO 97/43915 discloses the use of pulsed light to deactivate microorganisms in a contact lens container. Further, it discloses a method of receiving a portion of the pulsed light, generating an output signal in response to the portion of
1° pulsed light received, and determining whether the pulse of light is sufficient to effect a prescribed level of deactivation of microorganisms in the target area. WO 97/43915 discloses that the fluence-per-flash or the spectral content of the flashes can be measured for various regions of the spectrum
15 by using filters. There are long lists of possible pieces of equipment which might be incorporated into the measuring device, but no embodiment or example of such a device is described. WO 97/43915 suggests the use of an ultraviolet calorimeter to measure the energy in a light pulse, and states
20 that it is traceable to international standards; however, an ultraviolet calorimeter only provides a linear response to a specific pulsewidth, specific wavelength and specific intensity of light, and therefore is only traceable to international standards within those specified parameters. Outside of
25 those specified parameters the ultraviolet calorimeter typically has a non-linear response which is not traceable back to the calibration set-up for which there are international standards. Further, it is not appropriate to use an ultraviolet calorimeter to calibrate a photodetector to international
30 standards. An ultraviolet calorimeter only provides a single measurement of the total energy in the ultraviolet range, and does not provide any spectral information. The measurement it provides is an uncalibrated, relative output based upon the pulsed light energy, multiplied by the responsivity of the
35 detector, and multiplied by the bandpass and spatial filtration of the filter which provides the only radiation to the calorimeter. Further, the calorimetric sensor must have a rest period of a minimum of ten seconds between pulses since it is a thermal sensor. If the ultraviolet calorimeter were used
40 to provide instantaneous and in-line monitoring, the process of sterilizing using pulsed light sterilization would be either ineffective or so slow, it would not be desirable.
There still remains a need for a time-efficient, continuous in-line, and cost effective sterilization system comprising a
45 monitoring and control system and method of sterilization for products, particularly medical products, which can be used in the production line and which can measure and control the radiation to assure that every product is sterilized.
SUMMARY OF THE INVENTION
This invention provides a sterilization system comprising: a radiation source, and a monitoring system comprising a
55 sensor; and a timing means; wherein the measurement of energy by said sensor is substantially synchronized based on said timing means to the start and end of a pulse of radiation from said radiation source or to the start and end of the exposure of a product to said radiation.
go This invention further provides a method of measuring energy within a sterilization system wherein said sterilization system comprises a radiation source, and a monitoring system comprising a sensor, and a timing means, comprising the step of:
65 substantially synchronizing based on said timing means the measurement of energy by said sensor to the start and end of a pulse of radiation from said radiation
source or to the start and end of the exposure of a product to said radiation. This invention further provides a method of monitoring energy of a sterilization system wherein said system comprises a radiation source, and a monitoring system compris- 5 ing a sensor, and a timing means, comprising the step of: substantially synchronizing based on said timing means the measurement of energy by said sensor to the start and end of a pulse of radiation from said radiation source or to the start and end of the exposure of a 1° product to said radiation. The sensor is preferably an optical or electrical sensor or both. The optical sensor measures the radiation produced by the radiation source. The electrical sensor measures the voltage and/or current of the radiation source. It is preferred 15 that each sterilization system or monitoring system has at least one sensor, preferably an optical sensor, and more preferred that each sterilization or monitoring system has at least one optical sensor and at least one electrical sensor.
This invention further provides a monitoring system for a 20 radiation source, preferably for sterilization, the monitoring system comprises a sensor and a timing means. In one embodiment, this invention provides a monitoring system comprising one or more optical sensors which comprise an integrating sphere, or cosine receptor, light guide, and a 25 spectroradiometer with or without a timing means for measuring the radiation produced by the radiation source. Alternatively, in another embodiment, this invention provides a monitoring system comprising one or more electrical sensors, which comprise voltage and/or current monitors of 30 the electrical energy of the radiation source for producing radiation.
The sterilization system and method of this invention comprise a radiation source to sterilize products, preferably medical devices. The sterilization system and method can be 35 used to measure the radiation to which the product is exposed. The system and method described herein are well-suited for in-line manufacturing, and will provide accurate measurements of the radiation to which a product is exposed to assure that every product receives a sterilizing 40 dose of radiation.
The sterilization system and method, when the sensor is an optical sensor, can further be used to measure the radiation at multiple locations in the treatment area of the radiation source and provide a detailed two or three dimen- 45 sional mapping of the radiation to produce a spatial distribution characterization map of the source itself. In this modality the sterilization system is used as an automated source mapping system. The maps can be used to ensure consistency from one radiation source to another to maintain 50 uniformity in the sterilization dose in the manufacturing process.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a functional block diagram of a sterilization 55 system of this invention.
FIG. 2 shows an embodiment of the sterilization system of this invention.
FIG. 3 shows a spectroradiometric map of a single radiation source. 60
FIG. 4 shows spectroradiometric measurements of a lamp when the lamp was new and the same lamp after 2600 flashes.
DESCRIPTION OF THE INVENTION 65
The term "sterile" or "sterilization" as used herein means rendering an organism incapable of reproduction.
The term "radiation source" can mean one or more radiation sources unless otherwise indicated.
The term "ultraviolet radiation" means radiation having a wavelength or wavelengths between 200 nm and 400 nm.
The sterilization system is preferably used to sterilize medical products, preferably contact lenses in sealed containers or packages. The sterilization system comprises a radiation source, which can be any type of radiation source, including continuous and pulsed radiation sources. The preferred radiation source is a pulsed radiation source, for example, a flash lamp, which is a radiation source that has high intensity for a short time. The preferred pulsed light system is made by PurePulse Technologies, and is further described in WO 97-43915, U.S. Pat. Nos. 5,034,235, 5,786, 598, and 5,768,853, and 4,871,559, and 4,464,336 (Hiramoto), all incorporated herein by reference. The preferred radiation source in the sterilization system is further described in concurrently filed Brown-Skrobot, et al, U.S. patent application Ser. No. 09/259,758, entitled "Method of Sterilization", VTN-388, which is incorporated herein by reference. Presently, it is preferred that the pulsing, also referred to as flashing, delivers more than 18 mJ/cm2 ultraviolet radiation having wavelengths between 240-280 nm energy per pulse, preferably more than 30 mJ/cm2 ultraviolet radiation having wavelengths between 240-280 nm per pulse, to all the surfaces of the medical device to be sterilized. The preferred medical device is a contact lens, which preferably is in a sealed container or package. The description which follows will refer to contact lens packages; however, medical devices, other goods or products which may or may not be within containers or packages can be substituted for the contact lens package in the description.
The radiation per pulse may be from one or more radiation or light sources. (The terms light and radiation will be used interchangeably herein.) If the radiation is from more than one source, it is preferred that the sources pulse at the same time or at substantially the same time, that is, within 25 microseconds, more preferably within 5 microseconds and most preferably within 1 microsecond.
The sterilization system further comprises a monitoring system. The monitoring system preferably comprises a sensor. The sensor can be one or more optical or electrical sensors or both. The preferred embodiment comprises at least one optical sensor, more preferably two optical sensors.
The optical sensor preferably comprises a means for collecting the radiation, and means for measuring the radiation. The means for collecting can be a light guide, such as a liquid-filled light guide or a fiber optic, catadioptric mirror, light pipe, input slit, ultraviolet lens, integrating sphere, cosine receptor or multiples or combinations of the preceding list. An integrating sphere and cosine receptor are the more preferred. An integrating sphere is the most preferred.
Integrating spheres typically offer the largest field of view for collecting the radiation and are very durable. In comparison, a quartz fiber optic is less preferred, because it tends to undergo solarization; that is, lose its ability to transmit over time if it is directly exposed to the radiation. An integrating sphere, which comprises numerous durable reflective surfaces, collects at least a portion of the radiation, attenuates or magnifies the intensity of the radiation, and then sends the radiation via a light guide, preferably a fiber optic, to the means for measuring the radiation. Alternatively, the means for measuring the radiation may be incorporated into the means for collecting the radiation or visa-versa, but to limit the size of the means for collecting the radiation which preferably is located near the radiation
source, it is presently preferred to have a separate means for measuring the radiation and locate the means for measuring the radiation away from the radiation source.
It is important to limit the size of the means for collecting the radiation, because any object near the radiation source 5 may block some of the radiation which would otherwise reach the product which is very undesirable. The means for collecting the radiation may transfer the collected radiation to the means for measuring the radiation by mirrors, fiber optic, light pipe, ultraviolet lens, or the like; however, it is 10 preferred to use a fiber optic, because it offers flexibility in positioning as compared to methods which would require fixed alignment between the means of collecting the radiation and the means for measuring the radiation.
The integrating sphere is a hollow sphere, typically coated ^ internally with a white diffusing material having a defined spectral reflectivity in the interior of the sphere. The integrating sphere has at least one entry port. It is preferred that the integrating sphere has two or more entry ports. The number of entry ports preferably matches the number of 2o light sources; therefore, for the presently preferred sterilization system it is most preferred that the integrating sphere has two entry ports. The integrating sphere may be located anywhere as long as it receives at least a portion of the light; however, the integrating sphere is preferably located parallel 25 to the package to be exposed, between the light sources, but not blocking any direct light to the packages. In this preferred location, the entry ports are preferably located on the integrating sphere at from 30° to 60°, more preferably from 40° to 50°, and most preferably 45° from the midpoint of the 30 package to be exposed. In these preferred locations, the solid angle for the light cone entering each port will overlap the radiation source. The geometry of the entry port or ports is used to determine the energy per area of the radiation delivered to the packages. 35
Light traps, exit ports or gray reflector ports in the integrating sphere may be used to attenuate or multiply the radiation to meet the needs of the means for measuring the radiation. Preferably, the integrating sphere will transmit to the means for measuring the radiation enough energy to be 40 near the radiation saturation level for the means for measuring the radiation during each pulse in order to increase the signal to noise ratio. The reflectivity of the integrating sphere material is characterized in order to accurately calculate the sphere multiplier and maintain NIST traceability. 45 Also, the reflectivity of the integrating sphere preferably is as flat as possible across the entire spectral region of the radiation to be measured so that it is matched to the response of the means for measuring the radiation for appropriate gain control across the entire region. Stated differently, the inte- 50 grating sphere preferably transfers a substantially equal percentage of the radiation at all the wavelengths to be measured by the means for measuring the radiation. Integrating spheres provide to the means for measuring the radiation a much more equal percentage of the light over a 55 range of wavelengths than would be provided, for example, by filters. The preferred integrating sphere collects radiation at all the wavelengths generated by the radiation source.
The means for measuring the radiation preferably can measure total radiation, and the radiation at particular wave- 60 lengths or ranges of wavelengths. The means for measuring the radiation is preferably a spectrometer. It is preferred that the input into the spectrometer is a spread fiber optic input. The spectrometer preferably comprises a dispersive optical element and a photodetector. The dispersive optical element 65 can be transmissive or reflective as long as it disperses the radiation into the spectral components of the radiation.
Examples of dispersive optical elements which can be used in the spectrometer include diffraction gratings (blazed echelle, holographic, ion-etched), diffractive optics (lenses, windows, mirrors), binary optics (lenses, windows, mirrors), filters and mirrors (holographic, dichroic, narrowband, cuton, cut-off, thin film, ultraviolet, dielectric, blazed, diamond grooved), lenses and windows and prisms, and rulings, (glass, plastic, lithographic, microlithographic, radial, replicated), optical fibers (glass, liquid, dispersion shifted, plastic) as long as the optical element disperses the radiation into monochromatic radiation or into spectral components, preferably into spectral components. The preferred dispersive optical element is a diffraction grating reflector. The preferred diffraction grating reflector is a holographic grating or a ruled grating. The more preferred spectrometer comprises both a spread fiber optic input and a diffraction grating reflector. The dispersive optical element is preferably focused onto the photodetector.
The photodetector can be any kind as long as it can count the numbers of photons present at a certain range of the wavelength or wavelengths, for example, it can consist of photomultiplier tubes, photodiodes, and photocells in a Charge Coupled Device (CCD) array. The preferred photodetector is a photodetector array, more preferably a photodiode array, most preferably a metal oxide semiconductor (MOS) linear sensor, like the Hamamatsu S3901-256Q photodiode array in the Zeiss MMS miniature spectrometer. There can be any number of photodiodes, for example, at least 32 diodes, preferably there are 128 or more photodiodes, and more preferably 256 or more photodiodes in the array. In the most preferred spectrometer there are 256 photodiodes in an array on a single chip. The grating disperses the radiation into its spectral components which impinge on the array of photodetectors which count the numbers of photons present in the light at the wavelengths for which the photodectors are positioned. The sensor preferably has a spectral response extending down into the UV-C region, e.g. 200 nm, of at least 20 mA/W radiant sensitivity. The spacing of the photodetector array sensors preferably is 60 microns or less, more preferably between 20 and 60 microns. The sensor spacing preferably is calibrated for the x-axis (wavelength) using a second order polynomial fit equation. Preferably, the wavelength resolution of the photodetectors in the spectroradiometer is less than 10 nm, preferably less than 3 nm and is more preferably less than 1 nm. The preferred spectroradiometer, as described, can produce a spectral irradiance chart as a function of wavelength.
The means for measuring the radiation can be a single or small number of photodetectors, that is, less than 32, or less than 10 or even less than 3 photodetectors, which are sensitive to a narrow wavelength range of radiation. The photodetectors can be such that they are sensitive to particular wavelengths of radiation. This would be particularly suited for a radiation source, which produces a limited range of wavelengths, for example, lasers.
The preferred spectrometers are sensitive to the wavelengths between 185 nm and 900 nm. However, spectrometers having a larger or smaller array of photodetectors which are sensitive to a larger or smaller total range and/or larger or smaller incremental ranges of wavelengths within the total range of wavelengths can be used. The spectrometers are selected to have sensitivities to the wavelengths that need to be monitored. Presently, it is preferred that, at a minimum, the spectrometers are sensitive to wavelengths from 200 to 400 nm, more preferably from 200 to 300 nm and most preferably from 240 to 280 nm, because radiation of those wavelengths has the biggest impact on microorganisms.