U.S. patent number 3,837,805 [Application Number 05/292,615] was granted by the patent office on 1974-09-24 for apparatus for continuous sterilization at low temperature.
This patent grant is currently assigned to Wave Energy Systems Inc.. Invention is credited to Raymond M. G. Boucher.
United States Patent |
3,837,805 |
Boucher |
September 24, 1974 |
APPARATUS FOR CONTINUOUS STERILIZATION AT LOW TEMPERATURE
Abstract
An automatic method and apparatus to continuously surface
sterilize at temperatures below 75.degree. C any objects, parts or
components made of metal or heat sensitive materials. Said method
consists of treating materials first in a synergistically active
chemical solution in an ultrasonic tank, then of rinsing in a
second ultrasonic tank. The final step consists of drying the
processed material in a sterile atmosphere. The three different
processing steps taken place in a matter of minutes inside a
laminar flow positive pressure clean or white room. The apparatus
continuously delivers sterile parts or instruments ready for
packaging and sealing. Sterilized parts or instruments are not
physically or chemically affected by the process and do not contain
dissolved corrosive or toxic compounds.
Inventors: |
Boucher; Raymond M. G. (New
York, NY) |
Assignee: |
Wave Energy Systems Inc. (New
York, NY)
|
Family
ID: |
26803972 |
Appl.
No.: |
05/292,615 |
Filed: |
September 27, 1972 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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106739 |
Jan 15, 1971 |
3708263 |
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Current U.S.
Class: |
422/128;
422/301 |
Current CPC
Class: |
A61L
2/18 (20130101); A61L 2/00 (20130101); A61L
2/025 (20130101) |
Current International
Class: |
A61L
2/00 (20060101); A61L 2/18 (20060101); A61l
013/00 (); A61l 001/00 (); A61l 003/00 () |
Field of
Search: |
;21/12R,12A,54R,54A,DIG.2,58 ;134/1 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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947,699 |
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Jan 1964 |
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GB |
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947,700 |
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Jan 1964 |
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GB |
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Primary Examiner: Richman; Barry S.
Attorney, Agent or Firm: Shoemaker and Mattare
Parent Case Text
This application is a division of application Ser. No. 106,739,
filed Jan. 15, 1971, and now U.S. Pat. No. 3,708,263.
Claims
The embodiments of the invention in which an exclusive property or
privilege is claimed are defined as follows:
1. Low temperature sterilization apparatus for continuously and
quickly sterilizing objects without deleterious effect on the
objects, comprising:
a first container means,
a first, sporicidal solution in said first container means,
heater means operatively associated with the first container means
to maintain the temperature of the sporicidal solution at a
temperature within the range of 15.degree. to 70.degree. C,
track means adjacent the container means,
support means carried by said track means for supporting an object
to be sterilized and for placing the object in said sporicidal
solution,
means associated with said first container means to simultaneously
subject said sporicidal solution and said object to be sterilized
to ultrasonic energy while said object is in said sporicidal
solution to sterilize the object, said ultrasonic energy being
within the frequency range of 8 kHz to 900 kHz and having an
acoustic energy density level higher than 10 watts per liter in
liquid,
a second container means adjacent said first container means,
a sterile rinsing agent in said second container means,
said track means extending adjacent said second container means and
including means for conveying said object from said first container
means to said second container means and for placing said
sterilized object in said sterile rinsing agent to rinse said
object and remove substantially all traces of the sporicidal
solution therefrom,
means associated with said second container means to simultaneously
subject said sterile rinsing agent and said object to ultrasonic
energy while said object is in said sterile rinsing agent, said
ultrasonic energy being within the frequency range of 8 kHz to 300
kHz and having an acoustic energy density level higher than 10
watts per liter in liquid,
drying means adjacent said second container means,
said track means extending adjacent said drying means for movably
supporting said rinsed object in said drying means to dry said
object, means associated with said track means to continuously move
the support means and object into and through the first and second
container means and drying means, and
enclosure means surrounding said sterilization apparatus to confine
it in a decontaminated environment so that said object is delivered
in a dry, decontaminated and sterile condition ready for
decontaminated and sterile packaging.
2. Sterilization apparatus as in claim 1, wherein heater means is
associated with said second container means to maintain the
temperature therein in the range of from 45.degree. to 70.degree.
C.
3. Sterilization apparatus as in claim 1, wherein said sporicidal
solution comprises glutaraldehyde in a concentration of from .05
percent to 5 percent by volume.
4. Sterilization apparatus as in claim 3, wherein said sporicidal
solution includes dimethylsulfoxide in a concentration of less than
2 percent by volume.
5. Sterilization apparatus as in claim 4, wherein the size of said
first and second container means and said drying means and the rate
of movement of said object along said track means is such that said
object is disposed in said sporicidal solution, said rinsing agent
and said drying means equal amounts of time, said times being
within the range of from 2 to 30 minutes.
6. Sterilization apparatus as in claim 1, wherein said sterile
rinsing agent in said second container comprises germ free water in
combination with surface active agents.
7. Sterilization apparatus as in claim 6, wherein said surface
active agent comprises quaternary ammonium salt in a concentration
of less than .1 percent.
8. Sterilization apparatus as in claim 7, wherein heater means is
in said dryer means to maintain the temperature of processed
material inside said dryer means within the range of 70.degree. to
75.degree. C.
9. Sterilization apparatus as in claim 1, wherein means are
associated with said second container means for raising the
temperature therein.
10. Sterilization apparatus as in claim 9, wherein said means for
raising the temperature in said first and second container means
comprises an infrared heating element.
11. Sterilization apparatus as in claim 9, wherein said means for
raising the temperature in said first and second container means
comprises a microwave heating element.
12. Sterilization apparatus as in claim 9, wherein said means for
raising the temperature in said first and second container means
comprises an electrical heating element.
13. Sterilization apparatus as in claim 12, wherein means are in
cooperative association with each of said first and second
container means for supplying said chemical solutions thereto.
14. Sterilization apparatus as in claim 13, wherein said means for
subjecting said sporicidal solution, said sterile rinsing agent and
said object to ultrasonic energy comprises at least one
electro-acoustic transducer.
15. Sterilization apparatus as in claim 14, wherein said
electro-acoustic transducer comprises a piezo ceramic element.
16. Sterilization apparatus as in claim 14, wherein said
electro-acoustic transducer is positioned at the bottom of the
respective container means and generates a high intensity,
ultrasonic field upwardly through the sporicidal solution and said
sterile rinsing agent in said respective container means.
17. Sterilization apparatus as in claim 16, wherein said drying
means comprises an elongate housing open at opposite ends and
through which said object is passed from one end to the other end
thereof, blower means are associated with said housing to force air
through said housing in a direction opposite to the movement of
said object therethrough, heater means are operatively associated
with said drying means for raising the temperature in said housing,
and sterilization means is in said housing.
18. Sterilization apparatus as in claim 17, wherein said heating
means is disposed in the path of air from said blower means to said
housing, filter means is on said blower means for filtering air to
be circulated through said housing, and said sterilizing means
comprises ultraviolet lamps positioned in said housing.
19. Sterilization apparatus as in claim 18, wherein said track
means comprises conveyor means extending across the top of said
first and second container means and said drying means, said
conveyor means having sections of reduced elevation over said first
and second container means so that as said object is carried along
said conveyor means it is lowered into said container means when it
reaches said portions of reduced elevation.
20. Sterilization apparatus as in claim 19, wherein a perforate
basket means is supported from said conveyor, and said object is
carried in said basket means.
Description
This invention relates to a continuous sterilization method at low
and medium temperatures to process heat sensitive materials such as
hospital and medical plastic made disposables or delicate
electro-optical devices such as bronchoscopes or cystoscope which
cannot be autoclaved. Today hospitals, clinics and practitioner
offices use a large number of disposables made of heat sensitive
materials. Among these items are: syringes, suction catheters,
feeding and urinary drainage tubes, sutures, masks, nebulizer
tubes, surgical gloves, etc. To sterilize these heat sensitive
materials before, during or after packaging, most of todays
manufacturers use low temperature gas sterilization. This is indeed
at the moment the only practical method to handle low softening
point plastics, but, as well known, this method has numerous
drawbacks and limitations. Although several aerosols, vapours and
gases (see C. R. Philipps, Disinfection, Sterilization and
Preservation, pg. 669 Lea and Febiger, Philadelphia, 1968) have
been suggested in the past for gaseous sterilization,
ethylene-oxide is the only chemical used on a large scale for
industrial and medical applications. The advantages of
ethylene-oxide sterilization lie not in the speed, simplicity, or
economy of the treatment but rather in the fact that many types of
materials are sterilized with least damage to the material itself
when this technique is used. Among the drawbacks of this method is
the acute inhalation toxicity of this gas. Cases of acute human
exposures with nausea, vomiting, and mental disorientation have
been reported in the technical literature (R. E. Joyner, Archiv.
Environ Health, vol. 8, 700-710, May 2, 1964). As little as 3
percent of ethylene-oxide vapor in the air will support combustion
and will have explosive violence if confined. When mixed with
carbon dioxide (90 percent CO.sup.2) or various fluorinated
hydrocarbons the resulting mixture can in turn be mixed with air in
all proportions without any risk of explosion. However, these
mixtures are very slow acting compared to pure ethylene oxide. The
humidity of the air or gas mixture is another important factor to
take into consideration. Ethylene oxide sterilization is most rapid
at about 30 to 40 percent relative humidity and decreases as the
relative humidity approaches 100 percent. Highly desiccated
microorganisms are slow to respond to ethylene oxide sterilization.
Ethylene oxide is a very active chemical (alkylating agent) and it
sometimes alters the characteristics of the processed material. A
note of warning has been sounded, for instance, in the
sterilization of foodstuffs. It has been shown (E. A. Hawk and O.
Mickelsen, Science, vol. 121, no. 3143, 442-444, March 1955) that
various vitamins and amino acids were attacked by ethylene oxide.
More recently a food additive amendment to the Food, Drug and
Cosmetic Act discouraged the use of ethylene oxide due to the
presence of traces of toxic ethylene glycol which is one of the
by-products of the hydrolyzation of this chemical.
When processing certain organic materials (such as plastics) it has
been found that ethylene oxide is often soluble and may remain in
large amount after sterilization. Up to 4 percent ethylene oxide
has been detected by C. R. Philipps after gas sterilization of
rubber. Laboratory personnel have received chemical burns by
donning rubber shoes only 1 hour or so after they were sterilized.
More recently R. B. Roberts (MSR Fourth Quarter, page 3, 1968)
warned that ethylene oxide residues on surgical supplies could harm
medical personnel as well as patients. On rubber gloves, then can
burn the hands; and on tubes carrying blood, they will damage red
blood cells. Endotracheal tubes which are not properly aerated can
cause tracheitis or tissue necrosis. As a result of these
observations it was recommended that surgical plastic devices stand
at least 5 days at room temperature or 8 hours at 120.degree. F
before use. Since the time required for ethylene oxide
sterilization is not negligible (for instance, a 180 minute cycle
at 30.degree. C) an additional long deaeration period often renders
this method very expensive. It precludes anyway the development of
a continuous process for sterile packaging.
Special problems (see D. A. Gunther, J. R. Nelson, G. W. Smith,
Contam. Contr. vol. VIII, No. 8, 9-12, August 1969) are also
encountered in ethylene oxide bulk sterilization of disposable
articles such as catheters, irrigation sets, intravenous kits,
syringes etc. Most of these items are being packaged in clear
plastic film, such as hermetically sealed polyethylene. When a
sealed polyethylene package is placed in the environment of a
permeable sterilizing gas mixture, the gases will permeate the
polyethylene unit until they reach an equilibrium. This occurs when
the concentrations of the permeating gases become equal on the
inside and on the outside of the package. Since the residual air
within the package is trapped it also contributes to increase the
pressure inside the package. Thus, when the permeating gases reach
equilibrium, the total pressure in the package may become greater
than the outside pressure. This often results in package "swelling"
or even rupture. To cope with this problem various pressure cycles
are imposed upon the processed load. The pressure decrease is also
programmed to coincide with the pressure decrease within the
package as the permeable gases permeate out during the final stage
(post-diffusion period). This means a lengthy operation which can
last up to 8 hours when including water vaporization time, ethylene
oxide exposure and gas evacuation.
Despite all the above mentioned drawbacks, ethylene oxide
sterilization is the only technique used today at industrial scale
to "batch process" medical and hospital disposables. Other
non-thermal techniques of surface sterilization have been tried at
laboratory scale (particles radiation, electro-magnetic radiations)
but they always were too inefficient (long contact time required),
expensive or delicate to handle for industrial scale processing.
For instance, ultraviolet (at 2,650 A., 2,350 A. and 2,537 A., for
instance) irradiation can be under certain conditions quite
effective to destroy bacteria, vegetative cells or spores. The
energy level required to kill Bacillus Subtilis spores for instance
is said to be around 22,000 microwatt/sec/cm.sup.2. The difficulty
with ultraviolet radiation as a sterilizing agent is that it has a
very low penetrating power and micro-organisms are easily shielded
from it by soil or other materials through which it cannot
penetrate. The presence of agglomerates or "shadow zones" greatly
limits the use of this technique for surface sterilization of odd
shaped devices. In addition certain organic materials and plastics
are quite susceptible (polymerization or molecular degradation) to
high intensity UV irradiation. The same disadvantages exists when
one uses radioactive sources, such as cobalt 60 (gamma radiation)
or Xrays. The energy imparted by electrons, Xrays and gamma rays
results in ionizations (Compton effect) within the absorbed
material. This has a lethal effect on the majority of spores
according to dosage rate, presence of oxygen or protective
compounds, physiological state of the micro organisms, water
content and temperature. To achieve complete sterilization for
instance of Bacillus megaterium spores (A Tallentire, and E. L.
Powers, Rad Res, 20, 270-287, 1963) large does of energy
(5.10.sup.5 Rad) are needed and this means potential damage to the
irradiated material. More recently the synergistic effect produced
by combining heat and radiation (Contamination Control, 20-22, Feb.
1970) gave some hope of improving operational conditions.
Unfortunately, if the method provides a reduction in irradiation
time requirements (from 40 to 12 hours) at 105.degree. C it does
not seem to give encouraging results at temperatures below
105.degree. C.
It is therefore an object of the present invention to provide a
method to surface sterilize laboratory, medical, dental devices and
heat sensitive disposables in a matter of minutes rather than
hours.
It is also an object of the present invention to surface sterilize
within a short time period at low and medium temperatures within
the 15.degree. to 70.degree. C temperature range.
It is a further object of this invention to quickly "surface
sterilize" heat sensitive instruments and components in a
continuous process, which includes dipping the load of contaminated
objects in an ultrasonic bath synergistically activated by a
sporicidal agent, rinsing it in a second bath with sterile water,
drying it at a temperature below 75.degree. C inside an ultraviolet
tunnel and conveying the sterile material directly to the packaging
machine. All said automatic operations taking place in a germs-and
particles-free "white" room atmosphere.
It is a further object of this invention to continuously
surface-sterilize heat sensitive materials, tools, instruments or
components without leaving an amount of absorbed or dissolved
chemical which could create a toxicity problem when the processed
part is in contact with the human body.
It is a further object of this invention to continuously sterilize
heat sensitive materials in a manner such that none of the
physical, chemical, mechanical or structural characteristics of the
sterilized products will be altered during processing.
Other objects, advantages, features and uses of our invention will
be apparent during the course of the following discussion. To aid
in the understanding of the present invention, the potential
contribution of large amplitude sonic and ultrasonic waves to the
mechanism of sterilization in liquid phase when used alone or in
combination with chemicals such as glutaraldehyde or alkalynized
glutaraldehyde will first be reviewed briefly.
The release of high intensity acoustic waves (emission frequency
comprised between 8 kHz and 300 kHz) in contaminated liquids at
pressures equal or slightly higher than atmospheric pressure will
be discussed. Although a little complex at first sight, the
physical action of sonic or ultrasonic waves can be brought into
play in four major ways; namely, through large variations of
pressure, motion, heat degradation or electrical phenomena. The
acoustic energy is transmitted through the liquid by the back and
forth motion of the molecules along the direction of propagation.
This produces alternate adiabatic compressions and rarefactions,
together with corresponding changes in density and temperature.
In the case of a planar acoustic wave transmitted through a liquid
like water at an intensity of 10 watt/cm.sup.2, one can calculate
that the water molecules will oscillate with a motion amplitude of
the order of three microns (assume the emission frequency equal to
20 kHz). The molecular accelerations at the end of the molecular
excursions will be 5,000 times greater than the acceleration due to
gravity and considerable pressure changes (a few atmospheres) will
occur at any given point in the liquid 20,000 times each second.
Since the pressure is increased and decreased alternately, it is
understandable that during the negative pressure phase a point may
be reached at which the natural cohesive forces of the liquid will
be overcome. Then a new phenomenon known as "cavitation" takes
place. It corresponds to the formation and rapid collapse of small
cavities through the entire liquid. According to the energy density
level the cavities are filled with gas or vapor. In the latter
case, their collapse produces very large amplitude shock waves (up
to several hundred atmospheres) with local temperature up to a few
hundred degrees centigrade or more. Electrical discharges are also
believed to occur during the collapsing phase, this is called the
sonoluminescence effect.
Let us now consider what could happen to both the liquid molecules
and the micro-organisms (pathogens, viruses, vegetative cells or
spores) in contact with the liquid when submitted to an acoustic
field of the type here above described. Due primarily to the
effects of electrical discharges (ionization), "hot" points in the
liquid, and sharp pressure waves gradients, the molecular bonds of
water will be severed and free radicals OH and H will then be
produced.
Chemically active hydroxyl radicals and hydrogen atoms will be
available in the water solution to trigger several types of
chemical reactions which may lead to bactericidal compounds such as
water peroxide. (See I. E. Elpiner, Ultrasound, pg. 20, Chapter 2,
Consult. Bur. ed. New York 1964). If other chemicals are present in
the water such as glutaraldehyde, other molecular bond breakages
could take place which would favor for instance the combination of
aldehyde radicals with cells amino groups. With carbontetrachloride
one will observe, for instance, the production of free chlorine (S.
P. Liu, Chlorine Release Test for Caviation Activity Measurements,
Journal of Acoustical Society of America, Vol. 38, No. 5, 817-826,
Nov. 1965) and with potassium iodide the liberation of iodine (D.
E. Goldman and G. R. Ringe, Determination of Pressure Nodes in
Liquids, J. Acous. Soc. Am., Vol. 21, 270, 1949). It is known that
alkyl and aryl halides in aqueous suspension, irradiated at low
frequency, are hydrolysed to produce a halide ion and the
corresponding hydroxyl compound or ether (A. E. Crawford,
Ultrasonic Engineering, pg. 212, Chapter 9, London, Butterworths
Sci. Publ. 1955). The production of highly bactericidal compounds
such as ozone can also be the result of low frequency sonic
irradiation of oxygen saturated water. (M. Haissinsky and A.
Mangeot, Nuovo Cimento, 4:5, 1086, 1956). Nitrous acid, nitric acid
and nitrogen oxides can also be detected in small amounts during
the insonation of water saturated with air or nitrogen.
In short, it can be said that low frequency (8 to 300 kHz) high
energy density (higher than 10 watts/liter) acoustic emissions may
alone produce free radicals, atoms, ions or new chemicals with
strong bactericidal or sporicidal powers. Beside the production of
new chemicals or active radicals which could be toxic to most
pathogens, viruses or spores it is important to consider in detail
the other physical mechanisms which may affect the life of
unicellular or multicellular micro-organisms under ultrasonic
irradiation.
Large amplitude sonic and ultrasonic waves, inside the frequency
range previously stated, will considerably modify the ion exchange
processes through the cell membranes. This modification of the
diffusional process through inert or living membranes is well known
in the art. Along these lines there is, for instance, the early
work of J. H. Rees (Mast. Thesis, Mass. Inst. Techn., 1948) on the
influence of low frequency insonation (10 to 30 kHz) on the
dialysis constant. The enhanced membrane diffusion observed during
insonation can be interpreted as the complex result of the
radiation pressure, the acoustic pressure and cavitation on the
motion of individual ions or molecules. Each ion or molecule
receives a supplementary amount of energy in a high intensity
acoustic field, and it "boosts" its level of activity. This could
be, for instance, an extra "push" due to the passage of fast
travelling cavitation shock waves resulting from the collapse of a
resonant bubble. (I. Schmid, Acustica, 9:4, 321-326, 1959). But the
effect of acoustic waves on the membrane structure must also be
carefully considered. The enormous localized pressure waves which
can rip apart metal particles during intense vapourous cavitation
can indeed loosen macromolecular structures, such as the cell walls
of water-borne micro-organisms. By so doing, pressure waves
associated with the acoustic field can change the permeability of
the walls and membranes of living cells. This would explain, for
instance, why low frequency (8 - 300 kHz) high energy density
(above 10 watts/liter) ultrasound waves increase the sensitivity of
micro-organisms to disinfectants. It has been shown, for instance,
a few years ago (I. E. Elpiner, Gigiena I Sanit, USSR, 7:26, 1958)
that the sterilization of aqueous suspensions of E. Coli previously
irradiated at 20-25 kHz requires much lower concentration of
bactericides than the treatment of the same type of unirradiated
suspensions.
In other words, one can conclude that ultrasonic irradiation of
contaminated liquids at low frequency, high intensity, and with
reasonable contact time may lead either to the production of
compounds which would be toxic to the microorganisms in contact
with the liquid phase (through reaction at the active sites) or to
cells structure modifications which will be lethal to the same
micro-organisms.
Whatever the micro-organisms destruction mechanism is, ultrasonic
irradiation alone would rarely achieve a hundred percent kill. This
is understandable when one remembers that positive results can be
observed in practice only with huge amount of acoustic energy and
long exposure times (often several days).
It has been found in accordance with one aspect of the present
invention that a combination of liquid borne ultrasonic energy with
the chemical action of a glutaraldehyde solution provides an
extremely fast kill of pathogen bacteria, viruses, vegetative
cells, bacterial spores and spores. Such fast bactericidal and
sporicidal action takes place in a matter of minutes (1 to 30
minutes) thus enabling the continuous treatment of contaminated
parts when they are submerged during the right time period in the
ultrasonically activated solution of glutaraldehyde.
When using batches of hundred disposable syringes artifically
contaminated with Bacillus Subtilis (ATCC 6051) or Clostridium
sporogenes (ATCC 7955) it was found that a six minutes contact time
in a 1 percent solution of glutaraldehyde (pH5) at a temperature of
54.degree. C would give a hundred percent kill. The ultrasonic bath
was operated at a nominal frequency of 20 kHz while the density of
acoustic energy corresponded to approximately 15 watts per liter.
The average number of microorganisms per syringe was one million
before treatment. All other things being equal, a higher bath
temperature (70.degree. C) would reduce treatment time to less than
4 minutes.
It was also found that the sporicidal effect remained the same when
pH varied between 2 and 7 at the above mentioned temperatures, all
other experimental conditions being identical.
It was also found that the same bactericidal and sporicidal
activity was displayed for ultrasonically irradiated solutions (1
and 2 percent) buffered by suitable alkalinating agents to a pH of
7.5 to 8.5. In this latter case it was discovered that under the
experimental conditions hereabove defined it was possible to
decrease the hundred percent kill contact time down to eight
minutes at a temperature as low as 25.degree. C.
It was also found that higher ultrasonic frequencies (250 kHz for
instance) could also provide total destruction of spores on the
contaminated syringes with a slightly longer exposure (30 minutes
at 25.degree. C) time in a 2 percent solution of alkalinized
glutaraldehyde. In all cases the bactericidal and sporicidal
mechanisms seem to be the result of a synergistic phenomenon
between the chemical and ultrasonic energy since the killing effect
of the combined agents is always greater than the sum of the two
agents acting separately.
It was also found that the synergistic bactericidal and sporicidal
activity can be accelerated by adding traces of dimethyl sulfoxide
to the glutaraldehyde solution in the ultrasonic tank. For
instance, as previously mentioned, a batch of hundred disposable
syringes artifically contaminated with Bacillus Subtilis (ATCC
6051) were sterilized after a 6 minutes contact in a 1 percent
solution of glutaraldehyde (pH5) at 54.degree. C. The same batch of
syringes under identical conditions were sterilized in only 3
minutes when adding between 1 and 10 parts per million of
dimethylsulfoxide to the activated solution in the ultrasonic
tank.
This important time reduction could be due to a faster penetration
of activated chemical molecules or radicals through the spores
cortex. The above described experiments took place at a nominal
frequency of 20 kHz while the average density of acoustic energy in
the tank oscillated between 15 and 20 watts per liter.
It was also found that the concentration of glutaraldehyde could be
greatly decreased when operating at higher temperatures in the
60.degree. to 70.degree. C range. For instance, at 70.degree. C a
0.1 percent concentration of glutaraldehyde (pH 4.7) enables the
complete sterilization of contaminated disposable syringes in 5 to
6 minutes, thus providing results equal to those obtained with a 1
percent glutaraldehyde solution at 54.degree. C. In all these
experiments, the acoustic energy density in the tank remained
constant (around 15 to 20 watts/liter). The nominal frequency was
kept at 20 kHz.
The method of surface sterilization, object of the present
invention, consists of a three step system. The first step consists
of dipping the contaminated objects in an ultrasonic bath heated at
a temperature comprised between 25.degree. and 70.degree. C and
filled with a glutaraldehyde solution (maximum concentration 5
percent). The objects to be sterilized are contained in a tray (or
trays) made of perforated metal or plastic. Said tray is submerged
in the activated ultrasonic solution and moves slowly under the
influence of a "carrier-conveyor" system. The contact time into the
activated ultrasonic solution varies according to the nature of the
contaminant and the bath temperature, but it is in general
comprised between 2 and 30 minutes.
When the irradiated tray leaves the ultrasonic tank which contains
the glutaraldehyde solution traces of this chemical may remain
absorbed on the wet processed parts. From our analytical data
(spectroscopy) the glutaraldehyde content of the sterilized parts
is always less than one thousandth (1/1000) of the original amount
present in the processing tank. This indeed means a quantity far
below any potentially dangerous toxicity level. However, to
decrease this content down to a few gammas (parts per million) a
second ultrasonic tank is used with sterile water into which the
tray is dipped during a few minutes at a temperature comprised
between 54.degree. and 70.degree. C. This second ultrasonic tank
which performs a thorough washing operation of any remaining traces
of glutaraldehyde is the second step of the continuous
sterilization process object of the present invention. The last
step consists of a drying operation (a few minutes) into a medium
temperature tunnel. Said tunnel contains several powerful
ultraviolet lamps (intensity 10 watts/square foot) to maintain
sterile surface conditions while the warm stream of filtered air is
injected in the tunnel countercurrent to the direction of the
moving tray (or trays). The filtered air temperature is calculated
to maintain at all times a maximum temperature in the 54.degree. to
70.degree. C range inside the processed solid parts. Residence time
(a few minutes) in the tunnel is the same as the exposure time in
the ultrasonically activated solution tank and in the following
washing tank.
Having described our continuous liquid phase synergistic
sterilization process, we shall now describe, by way of a
non-limiting example, one embodiment of the apparatuses of the
present invention, as shown in the accompanying drawings.
FIG. 1 is a vertical cross-sectional side view of the three
apparatuses (synergistic bath, cleaning tank and dryer) which are
needed to apply the method object of our invention.
FIG. 2 is a vertical cross-sectional front view of the dryer-oven
taken along the line 2--2 as seen in FIG. 1.
As can be seen in FIG. 1, the system to continuously sterilize heat
sensitive parts consists of an ultrasonic tank 3 which contains the
sterilizing agents, said ultrasonic tank being followed by a second
ultrasonic tank 4 which rinses and eliminates most of the chemicals
absorbed on the processed material, said ultrasonic rinsing tank
being followed by a drying tunnel or oven 5 equipped with a
sporicidal source (ultraviolet lamps, microwave source, radiant or
X rays source).
The heat sensitive material 6 to be processed is placed into trays
of perforated metal or plastic baskets 7 which are suspended
through a hook 8 to a standard moving chain-wheel device 9 guided
by a rail support 10. The latter is designed in such a way that the
basket will be submerged at a few inches distance of the liquid-air
interface when the basket enters the areas above the ultrasonic
tanks 3 and 4.
The ultrasonic tanks 3 and 4 are in general of the same type and
they have the same dimensions to insure identical contact time for
the processed material in the liquid phases. The ultrasonic tank
will consist for instance of a stainless steel parallel-epipedic
tank 11 whose lateral walls (one or several of them according to
the type of operation) contain a heating element 12 (electrical
resistance, infrared, microwave, or dielectric, for instance. To
the bottom of the tank are fastened one or several standard
electroacoustic transducers 13 (piezo ceramic, ferrite or
magnetostrictive types) which irradiate in an upward manner and
create a high intensity ultrasonic field 14. To successfully apply
the process object of the present invention, the acoustic energy
density in the two tanks 3 and 4 must be greater than ten watts of
irradiated acoustic energy per liter.
The frequency of emission of the transducer elements in the first
tank 3 must also be comprised between 8 kHz and 900 kHz while the
frequency range in the rinsing tank 4 is restricted to the 8 kHz to
300 kHz region. Also located in the lower section below each tank
bottom is a power-generator G to drive the transducers array with
associated cooling and automatic frequency tuning or impedance
matching devices. The standard power generator could indeed be
packaged separately and placed at a remote location since this will
not affect the proper functioning of the transducers. As shown in
FIG. 1, the ultrasonic generator is activated from the main line
alternative current (120 or 220 volts, 60 cycles) through an
electrical connector 15. Each ultrasonic tank is equipped with a
draining-valve system arrangement 16. The first ultrasonic tank 3
is provided with an opening 17 which enables introducing fresh
sporicidal agent into the tank. An electric pump 18 introduces
automatically the active chemicals at the right dosage and
concentration into the filtered water main line 19. In the first
tank 3, the active cavitating solution will contain, for instance,
a solution 20 of glutaraldehyde whose concentration will be
comprised between 0.05 percent and 5 percent volume. Optionally and
according to the type of micro-organisms to be destroyed, a certain
amount of dimethylsulfoxide could be added (concentration lower
than 2 percent in volume). The temperature in the first tank 3
could vary between 15.degree. and 70.degree. C according to
solution pH and to the type of irradiated micro-organisms. In most
current applications for spores destruction, the first tank is
operated around 54.degree. C. The speed of the basket conveyor
system is adjusted to allow an average contact time in the
sterilizing solution comprised between 2 and 30 minutes according
to the type of application. The second ultrasonic tank 4 whose
function is to rinse away most of the chemicals absorbed on the
sterilized parts or components originally contains germ free water
21 with small amount of (less than 0.1 percent) surface active
agents such as cationic surface active agents or quarternary
ammonium salts. The second ultrasonic tank is always operated at a
temperature comprised between 45.degree. and 70.degree. C which
corresponds to maximum cavitation activity (L. D. Rosenberg,
Ultrasonic News, 16- 20, 4th quarter 1960).
After the sterilizing and rinsing operations, the baskets which
contain the sterile equipment enter into the drying tunnel 5. The
length of the drying tunnel is the same as the length of each one
of the two ultrasonic tanks 3 and 4, thus providing the same
contact time in the liquids and the dryer. The dryer tunnel 5, as
shown in FIG. 1, is only one of the possible embodiments of the
type of dryer apparatus to be used in our invention. As shown in
FIG. 2, the dryer tunnel in this example is of circular shape with
a slit longitudinal opening 22 at the top to allow the continuous
motion of the hooks 8 to which the basket 7 are attached. Three
openings 23 at the bottom of the tunnel are provided to introduce
warm filtered air into the tunnel. Warm air could be conveyed
through a piping system communicating with a central source of warm
filtered air, or it could be provided by means of individual
blowers 24 equipped with an internal heating element 25. The air
could be drawn directly from the processing room and filtered at
the blower inlet 26. The temperature inside the dryer tunnel is
adjusted for each application (taking into account convection,
conduction and radiation thermal effects) in such a manner that the
maximum temperature of the parts at the time they leave the tunnel
is always below 70.degree. to 75.degree. C. This objective can
indeed be achieved through the use of various forms of thermal
energy such as infrared, dielectric or electromagnetic (microwaves)
heating. Since the baskets which enter the dryer-tunnel 5 are
sterile and contain sterile material, it is necessary to sterilize
the tunnel atmosphere to avoid the deposition of airborne bacteria
or spores. To insure such a protection during the final drying
phase we already mentioned that we use warm filtered air. As a
supplementary protection, the dryer tunnel is equipped with
powerful ultraviolet lamps. In FIGS. 1 and 2, three such
ultraviolet lamps 27 are shown spaced each at 120.degree. from the
other. These ultraviolet lamps could, for instance, be of the
Hanovia type 94A-1 which emits 7.3 watts of UV energy at the 2,537
A. wave length. They will insure complete destruction of airborne
bacteria and spores during processing time in the tunnel. A
transformer 28 is shown connected to one of the ultraviolet lamps.
The basket 29 which leaves the tunnel, contains dry, sterilized
parts or components with traces of chemicals far below toxicity
level. At no time does the temperature of parts reach a level
higher than 70.degree. - 75.degree. C. Such parts and components
are ready to be fed manually or automatically to a packaging
machine under sterile conditions.
Also not shown in FIGS. 1 and 2, but obvious to a person skilled in
the art, the entire system described in FIGS. 1 and 2 is enclosed
inside a positive pressure clean or white room equipped with high
retention ULTRA HEPA filter modules. Horizontal laminar flow clean
rooms (class 100) of the type manufactured by Agnew-Higgins could
be used to operate the continuous sterilization system hereabove
described. With a view to increasing the efficiency of the white
room for bacteria and spores control, additional mobile LETHERAY
high intensity UV air sterilizers could be added inside the white
room specially in the vicinity of transfer points (i.e., between
tank 4 and tunnel 5, or between tunnel 5 exit and the packaging
sealing machine).
Without departing from the frame work of the present invention, it
must be well understood that, according to the desired results, the
present invention can be applied to variable load sizes of heat
sensitive materials at different temperatures within the specified
15.degree. - 70.degree. C range or at multiple gas pressures above
the irradiated liquid, and that, still without departing from the
scope of the invention, the structural details of the described
apparatuses, the dimensions and the shapes of their members (such
as the ultrasonic tank configuration) and their arrangement (the
position of ultraviolet tubes inside the dryer tunnel, for
instance) may be modified, and that certain members may be replaced
by other equivalent means (electrical heating elements replaced,
for instance by infrared radiant panels).
The teachings of the invention may be practiced within the
following parameters:
First Step: contact time in the sterilizing solution: 2 to 30
minutes Glutaraldehyde concentration: 0.05% to 5% in volume
Glutaraldehyde solution pH: 2 to 8.5 Dimethylsulfoxide
concentration: less than 2% in volume Acoustic energy density in
liquid: higher than 10 watts/liter Emission Frequency: 8 to 900 kHz
Temperature range in liquid: 15.degree.C to 70.degree.C Second
Step: Contact time in rinsing solution: 2 to 30 minutes
Concentration of surface active agents less than 0.1% in volume
Acoustic energy density in liquid: higher than 10 watts/liter
Emission Frequency: 8 to 300 kHz Temperature range in liquid:
45.degree.C to 70.degree.C Third Step: Contact time in dryer
tunnel: 2 to 30 minutes Temperature inside tunnel: adjusted to a
maximum of 70.degree.C to 75.degree.C in the processed material
leaving the dryer
* * * * *