WO2014082045A1

WO2014082045A1 - Plethysmograph array having signal shielding

Info

Publication number: WO2014082045A1
Application number: PCT/US2013/071735
Authority: WO
Inventors: John GODLESKI; Edgar DIAZ; Stephen Ferguson
Original assignee: President And Fellows Of Harvard College
Priority date: 2012-11-26
Filing date: 2013-11-25
Publication date: 2014-05-30

Abstract

A system includes a support structure, multiple shielded cages, each cage having walls, a base, and a ceiling supported by the support structure, made of a material to interfere with transmission of radiation between the cages. The cages are adapted to support a whole body plethysmograph for bodies containing an implanted transmitter, and wherein each cage is further adapted to hold a receiver to receive signals from the implanted transmitter from a body within the cage and provide the received signals outside the cage.

Description

Plethysmograph Array Having Signal Shielding Related Application

[0001] This application claims priority to United States Provisional

Application serial number 61/729,936, filed November 26, 2012, which is incorporated herein by reference. Government Funding

[0002] This invention was made with Government support under

Contract Number EP-P10983/C5530/56546 awarded by EPRI and grants R827353 and R832416 awarded EPA PM Center. The United States

Government has certain rights in the invention.

Background

[0003] A plethysmograph is an instrument for measuring changes in volume within an organ or whole body. One of the many uses of such an instrument is to measure effects of air contaminants on small animals. The animals are placed into a plethysmograph and are monitored. In some cases, the animals have transmitters implanted that monitor various parameters as part of an experiment. The transmitters transmit signals representative of the measured parameters to receivers. However, the receivers may receive many signals from multiple different animals and may not be able to distinguish which signals correspond to which animal.

Summary

[0004] A system includes a support structure forming cages made of a material to interfere with transmission of radiation between plethysmograph chambers in the cages. The chambers are adapted to serve as a whole body plethysmograph for bodies containing an implanted transmitter. Each cage is further adapted to hold a receiver to receive signals from the implanted transmitter from a body within the chamber in the cage and provide the received signals outside the cage. Brief Description of the Drawings

[0005] FIG. 1 is a block diagram of a system for supporting a plurality of plethysmographs according to an example embodiment.

[0006] FIG. 2 is a block diagram illustrating an airflow system according to an example embodiment.

[0007] FIG. 3 is a block diagram illustrating an airflow structure utilized to measure pressure within each chamber according to an example embodiment

Detailed Description

[0008] In the following description, reference is made to the

accompanying drawings that form a part hereof, and in which is shown by way of illustration specific embodiments which may be practiced. These

embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that other embodiments may be utilized and that structural changes may be made without departing from the scope of the present invention. The following description of example embodiments is, therefore, not to be taken in a limited sense, and the scope of the present invention is defined by the appended claims.

[0009] It has become apparent to the inventors that there is a substantial problem in many studies involving significant numbers of animals in whole body plethysmographs to be monitored. Interference between telemetry units in animals makes it difficult to separate out the signals transmitted by such units, and investigators are seeking solutions in a variety of ways. One of the solutions has been the development of telemetry systems with multiple frequencies, but the number of different frequencies that can be incorporated into these devices is limited. Inhalation exposure systems are common and often "home-made" devices may be constructed for specific studies. No known "home-made" system nor commercially available system is well suited for use with telemetry systems. Various embodiments described herein may have broad applicability because the system is a well-designed and well-made inhalation exposure system with unique features as described above and it is specifically engineered for use with telemetry devices.

[0010] A system 100 illustrated by a block diagram in FIG. 1, has multiple uses in animal physiological and toxicological research. The system 100 in one embodiment includes a table 1 10 to hold multiple chambers or whole- body plethysmographs 1 12, 1 14, 116, 118, 120, 122, 124, 126 for the study of the respiratory health effects of exposures of small animals 130 to test atmospheres (mixtures of gasses and/or particles in air, inhaled drugs, or any other aerosol). The system is adapted to hold multiple telemetry units 132 implanted into the research animals. Receivers 134 are positioned to be in close proximity to the telemetry units 132 to receive transmitted signals.

[0011] The table 110 may have multiple levels of racks 140 and dividers

142 forming cages to support and shield the whole-body plethysmographs that contain individual animals 130 with implanted biosignal telemetry transmitters 132. The cages also support individually separated signal receivers 134, which may be electrically or optically coupled to a controller 145 to collect data from the signal receivers 134. Wires or optical fibers may be used to connect the signal receivers to the controller 145 and are not shown to keep the diagram less cluttered.

[0012] In one embodiment, each whole-body plethysmograph with an animal and transmitter are positioned on top of the receiver 134 in a cage, such that each cage forms a faraday cage. Signals from other whole-body

plethysmographs in other cages do not interfere with each other. The cages in one embodiment are open at least from the front to allow visual inspection of the animals in the whole-body plethysmographs. Cages may also be open from the rear side of the table 110.

[0013] The table 110 may also have a lower level which contains air flow equipment 150. Each divided area or cage contains one

plethysmograph/telemetry unit as shown at 1 12, 1 14, 1 16, 118, 120, 122, 124, 126, and may optionally contain space for additional non-telemetry whole-body plethysmographs . Shielding by dividing walls 142 of individual paired transmitter/receivers is useful to prevent signal interference from one pair to another. The placement of additional, non-telemeterized whole-body plethysmographs within each divided area maximizes use of space to allow for optimum simultaneous exposures to the same aerosols. Placement of whole- body plethysmographs close together minimizes the potential for uneven exposure concentrations for different whole-body plethysmographs. The table may also be configured with two or more supply manifolds 155, 156 that can deliver either uniform aerosol concentrations to all of the whole-body plethysmographs or simultaneous delivery of different aerosol concentrations to different sets of chambers. If the inhalation exposure aspect of the table is not being used, the table may serve as a shielded support for continuous in-cage monitoring of physiological parameters by implanted telemetry biosensors and receivers. This table substantially improves the proximity in which the animals may be maintained while monitoring responses to pharmaceuticals or other test substances delivered to the animals by any means,

[0014] For inhalation toxicology, flow of vapors through all exposure whole-body plethysmographs may be maintained by a single vacuum pump 150 with rotameters 160 to control each whole-body plethysmographs flow separately. The vacuum connections to the plethysmographs have different mechanisms to minimize interference of pump pulsations with measurements of animal breathing flow patterns. To assure that the animals are exposed to the identical (and repeatable) test atmospheres composition, tubing with identical length and geometry may be used to connect all plethysmographs to aerosol inlet manifolds. The plethysmograph table may also be designed to minimize the interference of flow patterns generated within any given animal plethysmograph with measurements of the flow patterns for animals in other whole-body plethysmographs (by propagation through commonly connected tubing). This feature optimizes performance of devices to individually measure breathing flow characteristics of the test animals. HEPA filters may be used as a part of the pulse damping volume and also to protect the flow meters, valves and pump.

[0015] FIG. 2 is a block diagram illustrating an airflow system 200 according to an example embodiment. A pump 210 is coupled to a buffer chamber 215. Buffer chamber 215 holds a sufficient volume of gas to act as a pulse damper to the noise generated by the pump. In one embodiment, the buffer chamber 215 has a volume of approximately 359 lcc. In contrast, 12

plethysmograph chambers 220 are coupled to the buffer chamber via a manifold 225, with each plethysmograph chamber having a volume of approximately 1 141cc. The buffer chamber 215 volume in one embodiment is about three to four times the volume of a plethysmograph chamber. By reducing the noise generated by the pump 210, the quality of acquired signals may be greatly improved. In one embodiment, the buffer chamber 215 holds a sufficient volume of gas to maintain desired pressures and flows within each

plethysmograph chamber without transmitting pulses inherently generated by the pump 210.

[0016] In one embodiment, an exposure chamber 230 without flow may be coupled to the manifold 225 and used to compensate for changes in pressure in the system. The manifold may be simply a mechanism to distribute gas form the buffer chamber 215 to the plethysmograph chambers 220. Between the manifold and each buffer chamber in one embodiment, is a valve 235 and a rotameter or flowmeter 240. The valve and the flowmeter may be used to match flows through the plethysmograph chambers to minimize differential pressures between plethysmograph chambers. The rotameter may operate by varying a cross section area that the gas flows through.

[0017] FIG. 3 is a block diagram illustrating a structure 300 utilized to measure pressure within each chamber in one embodiment. A nipple 310 with an internal glass capillary 315 may be connected to a newly drill hole 320 in the manifold 225 (one for each manifold in the table) that serves as a cleaner way to measure the pressure inside each plethysmograph chamber 220. Lines 335 to each one of the transducers 340 that read the pressure differentials in the chambers 220 connected to that particular manifold 225. Each transducer or different pressure sensor 340 is coupled via a line 350 to observe the pressure inside each plethysmograph chamber 220. In one embodiment, lines 335 are coupled to the exposure chamber 230 which serves as a reference pressure for each differential pressure measurement. The exposure chamber 230 is in turn coupled to the manifold 225 via capillary 315.

[0018] The system may allow researchers to minimize the space required for physiological monitoring and exposing implanted animals to test substances by any means and specifically by inhalation of aerosols during drug

development/pharmaceutical or environmental toxicology research.

Experimental dose uniformity may be maximized using relatively shorter and more uniform delivery lines from whatever aerosol generation method is being used.

[0019] Various embodiments may also allow researchers to minimize the space required for physiological monitoring and exposing implanted animals to test substances by any means and specifically by inhalation of aerosols during drug development/pharmaceutical or environmental toxicology research.

[0020] The use of biosensors and telemetry systems to monitor physiological and toxicological responses of laboratory rodents to environmental agents, pharmaceuticals, and man-made products is consistently increasing with two well-known primary vendors already in this market and with high likelihood for more. Various embodiments may facilitate the use of these systems by providing a physical platform for their use and eliminates the major shortcoming of these systems. At the same time, various embodiments provide a means for use in inhalation studies by which gases or aerosols can be delivered to experimental animals.

[0021] Although a few embodiments have been described in detail above, other modifications are possible. For example, the logic flows depicted in the figures do not require the particular order shown, or sequential order, to achieve desirable results. Other steps may be provided, or steps may be eliminated, from the described flows, and other components may be added to, or removed from, the described systems. Other embodiments may be within the scope of the following claims.

Claims

1. A system comprising:

a support structure;

multiple shielded cages, each cage having walls, a base, and a ceiling supported by the support structure made of a material to interfere with transmission of radiation between the cages; and

wherein each cage is adapted to support a whole body plethysmograph for a body containing an implanted transmitter and to support a receiver, wherein each whole-body plethysmograph is adapted to permit signals from the implanted transmitter from to be received by the receiver within the cage.

2. The system of claim 1 wherein the cage walls comprise aluminum.

3. The system of claim 1 and further comprising a pump coupled to the whole-body plethysmographs by tubes.

4. The system of claim 3 wherein each tube is approximately the same length.

5. The system of claim 3 wherein multiple tubes are coupled to a single gas supply.

6. The system of claim 1 and further comprising an electrical connector coupled between each receiver and extending outside the corresponding cage.

7. The system of claim 6 and further comprising a controller coupled to each electrical connector to receive the signal from each receiver.

8. The system of claim 1 wherein the cages are open from a front to allow visual inspection of animals in the plethysmographs.

9. The system of claim 1 wherein each transmitter is coupled to transmit signals from multiple implanted sensors.

10. A system comprising:

a support structure;

multiple shielded cages, each cage having walls, a base, and a ceiling supported by the support structure made of a material to interfere with transmission of radiation between the cages;

a whole body plethysmograph supported by each cage, the whole body plethysmograph adapted to hold a body containing an implanted transmitter; and a receiver supported by each cage, wherein each whole-body plethysmograph is adapted to provide signals from the implanted transmitter to be received by the receiver within the cage.

1 1. The system of claim 10 wherein the cage walls comprise aluminum.

12. The system of claim 10 and further comprising a pump coupled to the whole-body plethysmographs by tubes.

13. The system of claim 12 wherein each tube is approximately the same length and is coupled to a single gas supply.

14. The system of claim 10 and further comprising an electrical connector coupled between each receiver and extending outside the corresponding cage to a controller.

15. The system of claim 10 wherein the cages are open from a front to allow visual inspection of animals in the plethysmographs.

16. The system of claim 10 wherein each transmitter is coupled to transmit signals from multiple implanted sensors.

17. A method comprising:

placing multiple whole body plethysmographs onto multiple shielded cages, each cage having walls, a base, and a ceiling supported by a support structure and made of a material to interfere with transmission of radiation between the cages;

placing a body containing an implanted transmitter into each of the plethysmographs; and

using a receiver supported by each cage, to receive signals from the implanted transmitter.

18. The method of claim 17 and further comprising using a pump coupled to the whole-body plethysmographs to provide gas to each plethysmograph via tubes.

19. The method of claim 17 and further comprising using an electrical conductor coupled to each receiver, the conductor extending outside the corresponding cage.

20. The method of claim 17 wherein each transmitter transmits signals from multiple implanted sensors and each receiver receives corresponding transmitted signals within each corresponding cage.