1. Field of the Invention
The present invention relates generally to biological testing and diagnostic devices and methods.
2. Description of the Related Art
Approximately 6.1 million people, most of them living in tropical, third-world countries, died of preventable, curable diseases in 1998. One of the factors contributing to these deaths is the lack of adequate diagnostic tools in the field. Developing countries do not have the medical resources to provide adequate lab testing and diagnostic procedures to many of their citizens. As a result, treatable disease often goes undiagnosed, leading to death or other serious complications. In addition, diagnostic tools may be unavailable in more developed countries during emergency situations, such as natural disasters, or during wartime.
Standard systems and methods of culturing samples and pathogens using Petri dishes and similar labwear are well known in the fields of microbiology and pathology. In such standard systems, a substrate (e.g., solid or semi-solid agar) is enclosed in an unsealed container designed to vent moisture and to lessen accidental introduction of contaminating microorganisms. A test sample possibly containing unknown microorganisms to be cultured is introduced into the container under sterile conditions. The container is then turned upside-down and placed into an incubator to control temperature, humidity, and other atmospheric conditions, and microorganisms in the test sample are allowed to grow. The upside-down dish/lid combination releases moisture from the dish, so that the moisture does not generally obscure the lid while viewing and moisture drops do not fall onto the surface of agar, contaminating the culture. Thereafter, the container is usually opened to view and confirm the presence of growing microorganisms. Often, this too must be done under sterile conditions because condensation on the lid of the container inhibits viewing, so the lid is removed to view the grown cultures. Various tests can then be applied to the cultured microorganisms in an attempt to identify them, with these tests often taking a significant amount of time. When the identity of a microorganism has been confirmed, this identity often leads to the selection of suitable medical treatment.
In certain embodiments, a device for providing portable biological testing capabilities free from biological contamination from an environment outside the device is provided. The device comprises a portable housing. The device further comprises a volume surrounded by the housing and sealed against passage of biological materials between the volume and the environment outside the device. The device further comprises a culture medium within the volume. The device further comprises one or more ports configured to provide access to the volume while avoiding biological contamination of the volume. The device further comprises a valve in fluidic communication with the volume and the environment. The valve has an open state in which the valve allows gas to flow from within the volume to the environment outside the device and a closed state in which the valve inhibits gas from flowing between the volume and the environment. The valve switches from the closed state to the open state in response to a pressure within the volume larger than a pressure of the environment outside the device.
In certain embodiments, a method of providing portable biological testing capabilities free from biological contamination from a local environment is provided. The method comprises providing components of a portable device. The components are configured to be assembled together to seal a volume within the device against passage of biological materials between the volume and an environment outside the device. The method further comprises sterilizing the components. The method further comprises providing a sterilized culture medium. The method further comprises assembling the components together with the sterilized culture medium within the volume, thereby forming an assembled device. The method further comprises sterilizing the assembled device, wherein sterilizing the assembled device comprises elevating a temperature of the assembled device. The method further comprises flowing gas from within the volume to the environment while the assembled device is at an elevated temperature. The method further comprises reducing the temperature of the assembled device to be less than the elevated temperature while preventing gas from flowing from the environment to the volume, thereby creating a pressure within the volume which is less than a pressure outside the volume.
In certain embodiments, a method of providing a sterilized volume with a reduced pressure is provided. The method comprises providing a device comprising a volume sealed against passage of biological material between the volume and a region outside the volume; and a valve which can be closed or opened. The valve inhibits gas from flowing from the region to the volume when closed. The valve allows gas to flow from the volume to the region when opened. The valve opens in response to a pressure within the volume being greater than a pressure within the region. The method further comprises sterilizing the volume, wherein said sterilizing increases a temperature within the volume and increases the pressure within the volume to be greater than the pressure within the region. The method further comprises opening the valve in response to the increased pressure within the volume, thereby allowing gas to flow through the valve from the volume to the region. The method further comprises cooling the volume and closing the valve, wherein said cooling decreases the pressure within the volume to create a pressure differential across the valve.
In certain embodiments, a method of using a biological testing device is provided. The method comprises providing a device comprising a housing. The device further comprises a volume surrounded by the housing and sealed against passage of biological materials between the volume and the environment outside the device. The device further comprises a culture medium within the volume. The device further comprises a port configured to provide access to the volume while avoiding biological contamination of the volume. The device further comprises one or more channels within the volume. The one or more channels is in fluidic communication with the port, with the culture medium, and with a region of the volume above the culture medium. The device further comprises a valve in fluidic communication with the volume and the environment. The valve has an open state in which gas flows from within the volume to the environment outside the device and has a closed state in which gas is inhibited from flowing between the volume and the environment. The valve is in the open state in response to a pressure within the volume larger than a pressure of the environment outside the device, thereby reducing the pressure within the volume. The method further comprises elevating a temperature of the volume. The method further comprises opening the valve while the volume is at an elevated temperature. The method further comprises reducing the temperature of the volume while the valve is closed, thereby reducing a pressure within the volume. The method further comprises introducing a liquid specimen to the port at an inlet pressure. The method further comprises flowing the liquid specimen from the port, through the one or more channels, to the culture medium. The flowing of the liquid specimen is facilitated by a pressure differential force between the inlet pressure at the port and the reduced pressure within the volume.
In certain embodiments, a device for providing portable biological testing capabilities free from biological contamination from an environment outside the device is provided. The device comprises a portable housing comprising an inner surface which slopes from a first portion of the housing to a second portion of the housing. The inner surface comprises a plurality of ridges extending along the inner surface from the first portion to the second portion. The device further comprises a volume surrounded by the housing and sealed against passage of biological materials between the volume and the environment outside the device. The device further comprises a culture medium within the volume. The device further comprises one or more ports configured to provide access to the volume while avoiding biological contamination of the volume.
In certain embodiments, a device for providing portable biological testing capabilities free from biological contamination from an environment outside the device is provided. The device comprises a portable housing comprising a substantially optically clear portion. The substantially optically clear portion comprises an outer surface and an inner surface. At least one of the outer surface and the inner surface is curved to form a lens. The device further comprises a volume surrounded by the housing and sealed against passage of biological materials between the volume and the environment outside the device. The device further comprises a culture medium within the volume. The device further comprises one or more ports configured to provide access to the volume while avoiding biological contamination of the volume.
These and other aspects and advantages of various embodiments will become apparent and more readily appreciated from the following description, taken in conjunction with the accompanying drawings.
Hereinafter, some embodiments according to the present invention will be described with reference to the accompanying drawings. Here, when one element is connected to another element, one element may be not only directly connected to another element but also indirectly connected to another element via another element. Further, irrelative elements are omitted for clarity. Also, like reference numerals refer to like elements throughout.
Unfortunately, the culture of test samples and simple identifying tests are often out of the reach of third-world medical practices or medical practices in the field. Without an established laboratory, it is often impossible to introduce a test sample into a container without contaminating the culture medium therein. In addition, adequate laboratory equipment (e.g., hoods, microscopes) is often unavailable. Furthermore, it may be impossible to view the cultured microorganisms without compromising sterility, and the lack of experience and instrumentation may preclude even simple tests intended to identify the cultured microorganisms.
A largely unappreciated problem in culturing of unknown microorganisms is that when unexpected organisms are discovered in a culture, the results are frequently dismissed as due to contamination. For example, until fairly recently, it was believed that human blood is essentially sterile except for unusual disease conditions such as sepsis. As a result, when bacteria were recovered from the blood of otherwise healthy patients, the results were ascribed to accidental contamination. It is now known that a small but significant number of bacteria constantly enter the circulatory system (e.g., from the gastrointestinal tract or the gums). This tendency to dismiss culture results as contamination opens our health system to a significant risk. For example, a genetically engineered microorganism (e.g., developed for warfare or terrorism) would look unusual in cultures, and may initially be dismissed as a mere contaminant. Certain embodiments described herein advantageously ensure freedom from contamination to a sufficient extent that unexpected culture results will not be dismissed as being due to contamination.
One object of certain embodiments described herein to provide an inexpensive and portable diagnostic tool by which pathogens can be identified in the field, so appropriate treatment may be administered quickly. For example, certain embodiments described herein provide a mobile medical testing device by which a first responder medical team can test for potential contaminants within a patient's blood. In certain embodiments, the device is advantageous because it allows individuals in the field to identify pathogens and other micro-organisms without a lab, a HEPA hood, or other sterile location, and without assistance from a pathologist.
Certain embodiments described herein advantageously provide a method for rapidly isolating infective organisms from a patient and quickly determining which drugs are effective against the isolated organisms, thereby facilitating more rapid and efficacious treatment. The shortened times in providing such diagnostic information using certain embodiments described herein can advantageously save hours or days which would be invaluable in stopping an epidemic. Certain embodiments described herein provide this functionality by maintaining an isolated environment in which pathogens can be cultured and observed. Certain embodiments described herein advantageously keep the cultured pathogens safely sealed during processing, thereby protecting users from exposure.
Under normal circumstances, the natural environment is unfit for the culture and identification of pathogens because there is a high likelihood that the sample will be contaminated by outside microbes and micro-organisms. In addition, many pathogens are “fastidious” and require specialized culture conditions. Preventing contamination of the culture environment is essential; otherwise the diagnostic value of the culture is compromised. Certain embodiments described herein address the problem of contamination by providing an isolated environment in which the environment can be readily modified so that a wide variety of pathogens can be cultured and observed by enclosing culture media in a sealed receptacle. By providing a sealed receptacle, when certain embodiments described herein culture unexpected microbes, the results can be trusted to have come from the patient, thereby allowing diagnosis and evaluation of unusual and/or mutated organisms.
While the sealed receptacle prevents contamination of the cultures grown therein, it creates several potential issues for the maintenance of an environment suitable for culturing pathogens. The interior of the sealed receptacle is a separate environment, sensitive to humidity, temperature, inner and outer pressure, the composition of the biological material under study, and the composition of the culture medium. As a result, certain embodiments described herein incorporate several features to allow manipulation of the interior environment so as to maintain suitable conditions for culture growth.
In certain embodiments, the housing 120 comprises a material that is generally impermeable to biological materials and gases penetrating therethrough. Examples of materials include, but are not limited to, glass, rubber, plastic or thermoplastic. In certain embodiments, the housing 120 is optically clear and comprises polystyrene. The housing 120 is sized to be portable or to be easily transportable. For example, in certain embodiments, the housing 120 is sized to be held in a user's hand. Larger housings 120 can be used in a research laboratory, with the housing 120 having one or more dimensions as large as 24 inches or larger.
In certain embodiments, the housing 120 further comprises one or more sealing members 178 between the first portion 172 and the second portion 174. For example, in certain embodiments, the one or more sealing members 178 comprises a gasket or an O-ring comprising an elastomer material (e.g., medical neoprene, silicone rubber, nylon, plastics). The material for the sealing member 178 is selected in certain embodiments to have little or no outgassing of toxins when gamma radiated, thereby avoiding poisoning of the culture medium 140 within the device 100. The seal 176 between the first portion 172 and the second portion 174 is generally impermeable to biological materials and gases penetrating therethrough. By providing a seal 176 which is generally impermeable to biological materials, the volume 130 within the housing 120 of certain such embodiments described herein is substantially sterile (e.g., substantially free of contamination) and can remain substantially sterile until a user selectively introduces biological material into the volume 130. In certain embodiments, the volume 130 contains air, nitrogen, carbon dioxide, or a noble gas. In certain such embodiments, the volume 130 does not comprise a significant amount of oxygen gas, thereby facilitating anaerobic growth conditions.
In certain embodiments, the first portion 172 comprises one or more protrusions 180 and the second portion 174 comprises one or more recesses 182 configured to engage with the one or more protrusions 180. For example, as schematically illustrated by
In certain embodiments, the first portion 172 and the second portion 174 are generally circular in shape. In certain other embodiments, one or both of the first portion 172 and the second portion 174 can have other shapes (e.g., generally square or generally rectangular) but with structures (e.g., walls, sides, extensions) configured to form a seal with corresponding structures of the other of the first portion 172 and the second portion 174. In certain embodiments, the first portion 172 is rotatable relative to the second portion 174 while maintaining the seal 176 between the first portion 172 and the second portion 174. In certain embodiments, the sealing member 178 comprises a lubricant (e.g., silicone grease) applied to a gasket or O-ring between the first portion 172 and the second portion 174, thereby improving the seal 176 between the first portion 172 and the second portion 174 while facilitating rotation of the first portion 172 relative to the second portion 174. In certain embodiments, the first portion 172 (e.g., a lid) is removably sealed onto the second portion 174 (e.g., a base) with the sealing member 178 (e.g., a gasket) therebetween, thereby forming the seal 176 (e.g., air-tight seal) while allowing rotational movement of the first portion 172 relative to the second portion 174.
In certain embodiments, the housing 120 comprises a plurality of dividers 184 in a bottom portion of the housing 120, as schematically illustrated by
In certain embodiments, the housing 120 can comprise a port covered by a membrane that allows passage of gas into and which is covered by a plastic cover. In certain embodiments, the plastic cover can be removed, allowing gas to pass through the membrane, to facilitate aerobic growth conditions within the volume 130. In certain embodiments, the plastic cover can remain in place, preventing gas from passing through the membrane, to facilitate anaerobic growth conditions within the volume 130.
In certain embodiments, at least a portion of the housing 120 is optically clear, thereby allowing a user to view at least a portion of the volume 130 within the housing 120. The housing 120 of certain embodiments comprises a transparent or optically clear viewing portion 188 (e.g., a window and/or a lens) to facilitate visualization of colonies cultured within the device 100. The viewing portion 188 of certain embodiments comprises polystyrene or another clear plastic material. In certain other embodiments, the viewing portion 188 comprises a sealing film (e.g., Parafilm®, EZ-Pierce™, or ThermalSealRT™ which is available from EXCEL Scientific, Inc. of Wrightwood, Calif.). In certain embodiments, the viewing portion 188 is incorporated in the first portion 172 or in the second portion 174 of the housing 120. In certain embodiments in which the first portion 172 of the housing 120 is rotatable relative to the second portion 174 of the housing 120, the viewing portion 188 is positioned on the first portion 172 away from the axis of rotation such that rotation of the first portion 172 changes the region of the volume 130 (e.g., changes the portion of the cultured colonies) viewable through the viewing portion 188. In certain embodiments, the viewing portion 188 comprises a molded sliding or hinged window on the housing 120 that extends over a moisture collection area of the device 100 (e.g., as shown in
Moisture condensed upon an inner surface 190 of the viewing portion 188 can obstruct or distort the view of the cultured colonies within the volume 130. In certain embodiments, the inner surface 190 of the viewing portion 188 of the housing 120 is sloped (e.g., by 5 to 10 degrees) to facilitate the flow of condensation along the inner surface 190.
In certain embodiments, the inner surface 190 of the viewing portion 188 comprises a plurality of ridges 192 along at least a portion of the inner surface 190.
The culture medium 140 of certain embodiments is configured to facilitate the growth and multiplication of cells or pathogens in a liquid specimen (e.g., containing blood, blood components, pus, urine, mucus, feces, microbes obtained by throat swab, sputum, or cerebrospinal fluid introduced to the culture medium 140. In certain embodiments, the culture medium 140 comprises a agar composition fortified with nutrients for optimum growth, but can be any of a number of solid or semi-solid culture materials gelled with agar or gelatin or the like. In certain embodiments, the culture medium 140 is liquid when heated and is poured or sprayed into the volume 130 under sterile conditions and is allowed to cool and to solidify. In certain embodiments, the culture medium 140 at least partially fills a bottom portion of the housing 120 and is in contact with an inner surface of the bottom portion of the housing 120. In certain embodiments, a releasing agent may be added or applied to the culture medium 140. In certain embodiments, the culture medium 140 is in liquid form.
In certain embodiments, the culture medium 140 has an upper surface where cells or pathogens can be introduced and allowed to grow and multiply. In certain other embodiments, the device 100 comprises one or more thin, hollow regions adjacent to the culture medium 140. These regions are configured to receive a liquid specimen containing cells or pathogens to be cultured within the device 100. In certain embodiments, the culture medium 140 is spaced from an inner surface of the bottom portion of the housing 120, thereby defining one or more thin hollow regions therebetween. In certain embodiments, the culture medium 140 comprises two or more portions (e.g., two or more layers) having one or more thin hollow regions (e.g., one or more discontinuities or cracks) therebetween. Thus, in certain embodiments in which the regions between the portions of the culture medium 140 are not significantly exposed to the atmosphere within the volume 130, a first, in vivo sample can grow in the discontinuity or between the layers of the culture medium 140 anaerobically while a second sample can grow aerobically on the upper surface of the culture medium 140. Colonies grown in these regions between the portions of the culture medium 140 in certain embodiments are readily observable through the culture medium 140.
U.S. Pat. No. 6,204,056, which is incorporated in its entirety by reference herein, discloses various embodiments in which a discontinuity between portions of the culture medium 140 is maintained to receive a liquid specimen and to provide a specialized environment that allows culture of cells, organisms, or anaerobes that will not normally grow on the upper surface of the culture medium 140. For example, in certain embodiments, the culture medium 140 comprises a first layer and a second layer having one or more generally flat and thin hollow regions therebetween. In certain embodiments, these regions comprise one or more elongate conduits (e.g., tubes) having a plurality of orifices (e.g., holes or slits) along the length of the one or more conduits and in fluidic communication with the one or more generally flat and thin regions, thereby providing a flowpath through which a liquid specimen can flow to the culture medium 140. In certain other embodiments, the device 100 comprises one or more porous or semi-permeable layers (e.g., membranes, meshes, nettings, or screens) between and physically separating the first and second layers of the culture medium 140 to form the region. The liquid specimen introduced to the region between the first and second layers is able to access one or both of the first and second layers.
As shown in
In certain embodiments, the segments 200 are integral portions of the housing 120 (e.g., extruded portions of the bottom portion of the housing 120). The bottom portion of the housing 120 can be etched, embossed, or otherwise machined to form the plurality of channels 202 in certain embodiments. In certain other embodiments, the segments 200 are portions of a member (e.g., a generally flat plate or layer) which is placed in the bottom portion of the housing 120 and which can be adhered to the bottom portion of the housing 120 prior to pouring the culture medium 140 over the member. In certain embodiments, the member can be placed over a first layer of the culture medium 140 and additional culture medium 140 can be poured over the member, thereby creating two layers of culture medium 140 with a discontinuity therebetween. In certain such embodiments, a region between the member and the bottom portion of the housing 120 can provide a conduit for fluid flow. The member of certain embodiments comprises a generally inert material (e.g., glass, ceramic, plastic) which does not significantly react with the other materials placed within the volume 130. The member can be etched, embossed, or otherwise machined to form the plurality of channels 202 in certain embodiments.
In certain embodiments in which the volume 130 has a reduced pressure as compared to the region outside the device 100, a pressure differential between the port 150 and the orifices 214 advantageously facilitates flow of the liquid specimen or reagent through the plurality of conduits 210. In certain such embodiments, the orifices 214 are sized such that the liquid specimen does not flow out of the orifices 214. Instead, the orifices 214 are blocked by the liquid specimen. In this way, certain embodiments described herein advantageously maintain a pressure differential between the port 150 and each unblocked orifice 214 to provide a pressure differential force which facilitates flow of the liquid specimen into the conduit 210 in a direction of the unblocked orifice 214.
Certain such embodiments advantageously provide three different types of regions in which pathogens may grow. A first region 220 in or near the first layer 140a of the culture medium 140 is a hospitable location for anaerobic pathogens to grow since this first region 220 is substantially isolated from the atmosphere above the culture medium 140. A second region 222 on top of the second layer 140b of the culture medium 140 is a hospitable location for aerobic pathogens to grow since this second region 222 is in fluidic communication with the atmosphere above the culture medium 140. A third region 224 along the sloping sides of the segments 200 is a hospitable location for aerophilic pathogens to grow since this third region 224 has a varying concentration of oxygen from the lower portion to the upper portion of the segment 200. Certain such embodiments advantageously provide more surface area for culture growth.
The liquid specimen or reagent in certain embodiments flows through the plurality of channels 202 by capillary action. In certain embodiments, the channels 202 are in fluidic communication with a region configured to have suction applied thereto. The suction and the capillary action draw the liquid specimen or reagent through the channels 202.
For example, in certain embodiments, each main channel 202a is also in fluidic communication with a generally circular channel 239 located near the periphery of the housing 120, as schematically illustrated in
The one or more ports 150 of certain embodiments are configured to provide access to the volume 130 without introducing other microbes, micro-organisms, or other contaminants into the volume 130. For example, the one or more ports 150 can be used to introduce a biological specimen into the volume 130, to apply suction to the volume 130, or to remove material (e.g., a portion of the cultured colony) from the volume 130 for additional study.
In certain embodiments, the insert 242 is removable from the hole 240 and reattachable to the hole 240, thereby providing access to the volume 130 (e.g., to introduce a biological specimen to the volume 130 or to remove a sample of a pathogen colony). In certain such embodiments, the port 150 is positioned on a top portion (e.g., lid) of the housing 120 or on a side portion of the housing 120. The insert 242 of certain such embodiments comprises a resilient material (e.g., neoprene, polyurethane, or another elastomer).
In certain other embodiments, the insert 242 is configured to be non-removable from the hole 240 and to be penetrated by a needle having a lumen therethrough (e.g., a sterile syringe needle 234), thereby providing access to the volume 130 (e.g., to introduce a biological specimen to the volume 130 or to remove a sample of a pathogen colony). The insert 242 is further configured to reseal itself upon removal of the needle 234 from the insert 242. In certain embodiments, the insert 242 comprises an elastomer material (e.g., neoprene or silicone). In certain embodiments, the port 150 comprises a plastic membrane which is pierced by a needle to access the volume 130.
In certain embodiments, the port 150 comprises a connector (e.g., a Luer-Lok® connector available from Becton, Dickenson and Company of Franklin Lakes, N.J.) and a blunt needle extending through the insert 242 and in fluid communication with the connector. In certain such embodiments, to introduce a liquid specimen through the port 150, a cap can be removed from the connector and a syringe can be coupled to the connector to inject the liquid specimen through the blunt needle. After the liquid specimen is introduced into the volume 130 through the port 150, the syringe can be removed, pulling the blunt needle with it and out of the port 150. The port 150 can self-seal upon removal of the blunt needle. Certain such embodiments advantageously avoid using a sharp needle so as to minimize the risk of accidental punctures of the user.
In certain embodiments, the port 150 is positioned so that selected portions of the volume 130 are accessible via the port 150. For example,
The valve 160 can be located on various portions of the housing 120. For example, in certain embodiments, the valve 160 is located on a first portion 172 of the housing 120, as schematically illustrated by
In certain embodiments, the valve 160 (e.g., a flapper valve) comprises a hole 260 through the housing 120 and a flexible member 262 (e.g., a flap) covering the hole 260. The hole 260 can be generally circular, generally oval, generally square, generally rectangular, or any other shape. In certain embodiments, the physical dimensions of the hole 260 are proportional to the volume 130 of the device 100 to be vented. In certain embodiments, the flexible member 262 comprises a plastic layer which is generally impermeable to gases penetrating therethrough. A first portion of the flexible member 262 is configured to remain stationary (e.g., affixed to the housing 120) during operation of the device 100 and a second portion of the flexible member 262 is configured to move (e.g., affixed or not affixed to the housing 120) during operation of the device 100.
In certain embodiments, the valve 160 advantageously avoids significant increases of the pressure within the volume 130 (e.g., due to increased temperature within the volume 130 or due to gas released by the pathogen culture). For example, because the volume 130 is sealed, assembly of the device 100 can result in a pressure within the volume 130 which is higher than atmospheric pressure. This increased pressure at the ports 150 would effectively oppose introduction of the liquid specimen into the volume 130. The valve 160 of certain embodiments described herein advantageously is means for reducing the pressure within the volume 130 sufficiently so that the liquid specimen can be easily introduced into the volume 130, thereby facilitating use of the device 100. In certain embodiments, the valve 160 advantageously maintains a relatively constant pressure within the volume 130 by allowing excessive gas to escape. By responding to increased pressure within the volume 130, certain embodiments described herein allow the pressures inside the housing 120 and outside the housing 120 to equilibrate.
In certain embodiments, the valve 160 further comprises a filter 270 configured to inhibit contaminants from passing through the valve 160 while allowing one or more gases to flow therethrough.
In certain embodiments, the filter 270 is differentially permeable such that it is configured to inhibit at least a first gas from flowing therethrough while allowing at least a second gas to flow therethrough. For example, the filter 270 of certain embodiments can discriminate between various atmospheric gases and water vapor, thereby increasing or decreasing the humidity within the volume 130. As another example, the filter 270 of certain embodiments can discriminate between oxygen and other gases, thereby maintaining, facilitating, or retarding an anaerobic or other specialized atmospheric condition within the volume 130.
In certain embodiments, the filter 270 is sealed with a protective, substantially impermeable plastic layer prior to use. The plastic layer can serve in certain embodiments as the flexible member 262. In certain such embodiments, a user places the device 100 in condition for use by peeling a portion of the plastic layer away from the housing 120, releasing a strong seal between the plastic layer and the housing 120 and allowing the plastic layer to return to its sealed position but only slightly resting on the housing 120, to allow the plastic layer to respond to pressure differentials between the volume 130 and the environment 110 by moving to either open or close the valve 160. In certain such embodiments, the plastic layer has a small tab to facilitate the user peeling the plastic layer back. In certain embodiments, the flexible member 262 can remain in place allowing venting of the volume 130 while facilitating anaerobic or microaerophilic growth conditions in the device 100. In addition, the flexible member 262 can be completely removed from the device 100, thereby leaving the hole 260 covered with the filter 270, which can be configured to allow oxygen to flow therethrough, thereby facilitating aerobic growth conditions within the volume 130. Alternatively, in certain embodiments, the flexible member 262 is configured to be closed during growth within the volume 130, thereby facilitating anaerobic growth conditions within the volume 130.
In certain embodiments, the device 100 comprises a moisture absorbent material 280 (e.g., foam, sponge, or other porous material) within the volume 130 and configured to receive moisture condensed onto an inner surface 190 of the housing 120 (e.g., on the viewing portion 188).
In certain embodiments, the device 100 comprises an elongate member 284 contacting the inner surface of the housing 120 and movable along the inner surface 190 to wipe moisture from at least a portion of the inner surface 190. In certain embodiments, the elongate member 284 facilitates removal of moisture from the inner surface 190 of the housing 120. For example, in certain embodiments, the elongate member 284 comprises the moisture absorbent material 280.
One corner of the second portion 174 comprises a trough 282 containing the moisture absorbent material 280 therein. The first portion 172 of the housing 120 is rotatable relative to the second portion 174 of the housing 120 and the first portion 172 comprises a plurality of ridges 192 along the inner surface 190 of the first portion 172. When the first portion 172 is in a first position (e.g., a “home” position), at least a portion of the plurality of ridges 192 extend over the trough 282 such that condensation can flow along the ridges 192 to drop onto the moisture absorbent material 280. The first portion 172 of the housing 120 comprises a viewing portion 188 having a sliding plastic window to allow access to the moisture absorbant material 280. The kit 300 of certain embodiments further comprises a vacuum source 302 (e.g., Vacutainer®) on one side of the kit 300 configured to be placed in fluidic communication with the volume 130 via a port 150 on the second portion 174. In certain embodiments, the second portion 174 extends beyond the first portion 172 to provide support for various other components of the kit 300 (e.g., vacuum source 302, trough 282).
In the following description of various methods in accordance with certain embodiments described herein, reference is made to various components of the device 100 as described above. However, in accordance with certain embodiments, the methods described herein can be used with other components and other devices with other structures than those described above. In addition, while the methods are described below with operational blocks in particular sequences, other
In certain embodiments, providing components of a portable device 100 in the operational block 410 comprises providing a portable housing 120, a sealed volume 130 surrounded by the housing 120, one or more ports 150 configured to provide access to the volume 130, and a valve 160 in fluidic communication with the volume 130 and the environment 110. Devices 100 comprising other sets of components are also compatible with certain embodiments described herein. In certain embodiments, providing the components in the operational block 410 further comprises providing a culture medium 140. In certain such embodiments, sterilizing the components in the operational block 420 comprises sterilizing the culture medium 140. Thus, providing a sterilized culture medium 140 in the operational block 430 is performed as part of the operational blocks 410 and 420.
In certain embodiments, sterilizing the components in the operational block 420 comprises heating the components. In certain other embodiments, sterilizing the components comprises exposing the components to gamma radiation or ultraviolet radiation. Similarly, in certain embodiments, sterilizing the assembled device 100 in the operational block 450 comprises heating the assembled device 100. In certain other embodiments, sterilizing the assembled device 100 comprises exposing the assembled device 100 to gamma radiation or ultraviolet radiation. In certain embodiments, exposing the assembled device 100 to gamma or ultraviolet radiation elevates the temperature of the assembled device 100. In certain embodiments, the elevated temperature is greater than a temperature of the assembled device 100 prior to being sterilized.
In certain embodiments in which the device 100 comprises a valve 160 as described herein (e.g., a one-way valve or flapper valve), elevating the temperature of the assembled device 100 in the operational block 450 causes gas to flow from within the volume 130 to the environment 110. Thus, in certain such embodiments, the operational block 460 is performed as part of the operational block 450. Furthermore, in certain such embodiments, reducing the temperature of the assembled device 100 to be less than the elevated temperature in the operational block 470 causes the pressure within the volume 130 to be less than a pressure outside the volume 130. Similarly, in certain embodiments in which the device 100 comprises a valve 160 as described herein, the valve 160 closes once there is no longer a pressure differential force keeping the valve 160 open. Since the closed valve 160 prevents gas from flowing from the environment 110 to the volume 130, reducing the temperature of the assembled device 100 after the valve 160 is closed results in the pressure of the volume 130 reducing to be less than a pressure in the environment 110 outside the volume 130.
Certain embodiments described herein advantageously provide a device 100 having a sterilized volume 130 with a reduced pressure therein. The device 100 of certain such embodiments can be shipped while having the reduced pressure in the volume 130, thereby relieving the end user from having to create the reduced pressure in the volume 130. In addition, certain such embodiments advantageously create the reduced pressure during the sterilization process, thereby reducing the number of steps needed to provide the device 100.
In certain embodiments, the method 400 further comprises providing a desiccant material (e.g., calcium carbonate) and placing the assembled device 100 and the desiccant material within a container (e.g., a plastic bag), and sealing the container against passage of biological materials and water vapor between the assembled device and a region outside the container. The container of certain embodiments is generally impermeable to biological materials and water vapor penetrating therethrough. In certain such embodiments, sterilizing the assembled device in the operational block 450 is performed while the assembled device 100 is sealed within the container. In certain embodiments, the desiccant material advantageously absorbs water vapor within the container (e.g., plastic bag), including water vapor emitted from the device 100 while the device 100 is being sterilized (e.g., by gamma radiation).
In certain embodiments in which the device 100 comprises a valve 160 as described herein (e.g., a one-way valve or flapper valve), sterilizing the volume 130 (e.g., by irradiating the volume 130 with gamma radiation or ultraviolet radiation) and increasing the temperature within the volume 130 in the operational block 520 increases the pressure within the volume 130, thereby causing the valve 160 to open and gas to flow from within the volume 130 to the region outside the volume 130. Thus, in certain such embodiments, the operational block 530 is performed as part of the operational block 520. Furthermore, in certain such embodiments, the valve 160 closes once the pressure within the volume 130 and outside the volume 130 equilibrizes. Cooling the volume 130 in conjunction with the closed valve 160 in the operational block 540 causes the pressure within the volume 130 to be less than a pressure outside the volume 130 since the closed valve 160 prevents gas from flowing from the region outside the volume 130 to within the volume 130. Thus, a pressure differential across the valve 160 is formed.
In an operational block 620, the method 600 further comprises elevating a temperature of the volume 130. In an operational block 630, the method 600 further comprises opening the valve 160 while the volume 130 is at an elevated temperature. In an operational block 640, the method 600 further comprises reducing the temperature of the volume 130 while the valve 160 is closed, thereby reducing a pressure within the volume 130. In an operational block 650, the method 600 further comprises introducing a liquid specimen to the port 150 at an inlet pressure. In an operational block 660, the method 600 further comprises flowing the liquid specimen from the port 150, through the one or more channels 202, to the culture medium 140. Flowing of the liquid specimen is facilitated by a pressure differential force between the inlet pressure at the port 150 and the reduced pressure within the volume 130. In certain other embodiments, the method 600 includes other operational blocks and/or has other sequences of operational blocks.
In certain embodiments, the liquid specimen comprises blood, blood components, pus, urine, mucus, feces, microbes obtained by throat swab, sputum, cerebrospinal fluid, or other biological material from a patient to be diagnosed. The port 150 can be configured to receive a needle comprising a lumen (e.g., a syringe needle or blunt needle as described herein) through which the liquid specimen is delivered to the volume 130. For example, the port 150 can provide access through the housing 120 into the volume 130, as described herein. In certain embodiments, the port 150 is in fluidic communication with the one or more channels 202, as described herein. For example, the port 150 can be configured to be penetrated by the needle to introduce the liquid specimen to the volume 130 and to reseal itself upon removal of the needle from the port 150. In certain embodiments, the port 150 comprises an access portion 228 within the volume 130 and in fluidic communication with the one or more channels 202. In certain such embodiments, the access portion 228 provides fluidic access to the channels 202 such that a liquid specimen introduced to the access portion 228 flows through the channels 202 to be distributed along the culture medium 140. As described herein, in certain embodiments, the one or more channels 202 provides fluidic communication between the port 150 and the region of the volume 130 above the culture medium 140. Thus, a difference in pressure between the port 150 and the region of the volume 130 above the culture medium 140 creates a pressure differential force on the liquid specimen which facilitates the flow of the liquid specimen through the one or more channels 202. Since in certain embodiments the one or more channels 202 comprise a plurality of orifices 214 in fluidic communication with the culture medium 140, the liquid specimen flowing through the one or more channels 202 is distributed across the culture medium 140.
In certain embodiments, the liquid specimen is introduced to the port 150 at an inlet pressure greater than or equal to atmospheric pressure. In certain other embodiments, the liquid specimen is introduced to the port 150 at an inlet pressure less than atmospheric pressure but greater than a pressure within the volume 130.
Certain embodiments described herein provide rapid and even distribution of the liquid specimen through the one or more channels 202. The liquid specimen can be rapidly distributed throughout the culture medium 140, facilitated at least in part by the pressure differential force between the volume 130 and the port 150 through which the liquid specimen is introduced to the volume 130.
In the use of standard laboratory culturing dishes (e.g., Petri dishes), culture media such as agar typically release moisture, and moisture and various gases are typically produced by the microbes grown on or in the culture medium. Because moisture is viewed as an enemy of growing discrete colonies (which is a fundamental goal of microbiology), Petri dishes are intended to allow this moisture to evaporate away from the dish and to allow the gases to escape the dish. Therefore, prior systems have not envisioned a purpose for a valve as described herein.
Petri dishes in incubators also have the possibility of cross contamination. In addition, the lids of Petri dishes are typically opened periodically to monitor the culture growing therein. These standard laboratory methods invite contamination, and complicated guidelines have been adopted to deal with reducing the likelihood of contamination, but some possibility of contamination remains. Standard practice now involves calling anything unexpected a contaminant.
Certain embodiments described herein advantageously provide a sealed volume 130 which is sterilized after the device 100 is assembled and filled with the culture medium 140, ready for use. To sterilize the assembled device 100, radiation (e.g., gamma radiation or ultraviolet radiation) can be used, however, the sterilization process can create heat with consequent pressure differences between the volume 130 and outside the device 100, with resultant problems in use.
The valve 160 of certain embodiments described herein provides a means to control the internal pressure of the volume 130. The valve 160 of certain embodiments is automatic, sensitive to slight pressures, and sufficiently inexpensive to be used in a disposable device 100.
In certain embodiments in which the valve 160 comprises a plastic flapper valve, the device 100 advantageously provides both an aerobic and anaerobic test in one device 100. In certain such embodiments, the flexible member 262 (e.g., flap) can be removed leaving the remaining filter 270 on the device 100. If the filter 270 is configured to allow oxygen to enter the volume 130, an aerobic condition can be created within the volume 130. If the flexible member 262 is left on the device 100, an anaerobic condition can be created within the volume 130. In certain other embodiments, this capability could be provided by a separate port dedicated for this purpose. Such capabilities are not provided by existing culturing dishes.
Certain embodiments described herein allow visualization of the various cultured colonies within the device 100. In addition, certain embodiments described herein facilitate the visualization of the effects of various proposed drugs or other treatments on the cultured colonies. For example, the device 100 of certain embodiments is ideally suited for typical Kirby-Bauer diffusion tests in which small samples of various substances (e.g., drugs, reagents) are placed on filter paper discs or similar medium and are allowed to diffuse into the culture medium 140. In certain embodiments, the discs can be applied to the culture medium 140 using an assembly configured for this purpose, as described more fully in U.S. Pat. No. 6,204,056, which is incorporated in its entirety by reference herein. For example, a test grid assembly containing drug samples can be arranged within the device 100 and configured to be brought into contact with the culture medium 140 in corresponding partitioned regions 186 when desired. Alternatively, the plurality of channels 202 can be utilized to deliver a pattern of test substances in a predetermined pattern. Combinations of the assembly and plurality of channels 202 can be used to deliver a variety of test compounds to various portions of the culture medium 140 to mimic a complex treatment regime. Certain embodiments described herein advantageously allow a user to follow a series of relatively simple instructions without having to understand the underlying complexity.
Certain embodiments described herein, particularly in combination with the partitioned culture medium 140 described above, advantageously provide a simple way to interpret the results of the analysis. For example, in certain embodiments, the same liquid specimen can be introduced to each of the partitioned regions of the culture medium 140 and each partitioned region can be exposed to a different test substance or drug. In certain such embodiments, the appearance of the partitioned regions of the culture medium 140 can be indicative of the microorganisms (e.g., bacteria, viruses) in the liquid specimen and/or the efficacy of various drugs (e.g., antibiotics) on the microorganisms of the liquid specimen. In certain embodiments, the device 100 can be used with a listing of possible resulting patterns of the appearance of the partitioned regions of the culture medium 140 (e.g., clear regions, regions that show growth, regions that show a particular color resulting from interactions of pathogens and indicator substances). By matching the appearance of the device 100 to one of the patterns in the listing advantageously allows the user to make a complex diagnosis or determination using the device 100.
While the methods are described herein with reference to various configurations of the device 100 and its various components, other configurations of systems and devices are also compatible with embodiments of the methods described herein. Any method which is described and illustrated herein is not limited to the exact sequence of acts described, nor is it necessarily limited to the practice of all of the acts set forth. Other sequences of events or acts, or less than all of the events, or simultaneous occurrence of the events, may be utilized in practicing the method(s) described herein.
Certain aspects, advantages and novel features of the invention have been described herein. It is to be understood, however, that not necessarily all such advantages may be achieved in accordance with any particular embodiment of the invention. Thus, the invention may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein.
Various embodiments of the present invention have been described above. Although this invention has been described with reference to these specific embodiments, the descriptions are intended to be illustrative of the invention and are not intended to be limiting. Various modifications and applications may occur to those skilled in the art without departing from the true spirit and scope of the invention as defined in the appended claims.
This application is a divisional of U.S. patent application Ser. No. 11/836,541, filed on Aug. 9, 2007 and incorporated in its entirety by references herein, which claims the benefit of U.S. Provisional Patent Appl. No. 60/822,004, filed Aug. 10, 2006, which is incorporated in its entirety by reference herein.
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Number | Date | Country | |
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Parent | 11836541 | Aug 2007 | US |
Child | 13032396 | US |