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EP-3629714-B1 - WIRELESS AUTOMATED ANIMAL MONITORING SYSTEM

EP3629714B1EP 3629714 B1EP3629714 B1EP 3629714B1EP-3629714-B1

Inventors

  • SCHERER, AXEL
  • PETILLO, PETER A.
  • CHEN, SAMSON
  • EMAMI, Azita

Dates

Publication Date
20260513
Application Date
20180523

Claims (14)

  1. A system comprising: a container configured to contain a plurality of laboratory animals forming a group-housed social environment, the container comprising at least one radiofrequency transceiver, the radiofrequency transceiver being a wireless radiofrequency transceiver; and a sensor configured to read at least one monitorable condition of a laboratory animal of the plurality of laboratory animals within the group-housed social environment, the sensor configured to be attached to the laboratory animal, the sensor comprising at least one radiofrequency transmitter, wherein said sensor is of the type powered by on-chip inductive currents and said sensor has a size such to be injectable in the laboratory animal, wherein the radiofrequency transmitter comprises a transmitter coil, the radiofrequency transceiver comprises a transceiver coil, and the radiofrequency transmitter and the radiofrequency transceiver are configured to communicate through near-field inductive coupling between 800 and 900 MHz, wherein the transceiver coil is configured to couple to the transmitter coil to power the sensor and a current flow through the transceiver coil induces a corresponding current in the transmitter coil when the transceiver coil and the transmitter coil are critically coupled at a frequency of 800-900 MHz; and wherein the radiofrequency transmitter is configured to communicate with the radiofrequency transceiver by reflecting the input power in short pulses resulting in digital pulse trains comprising a series of changes in reflective power.
  2. The system of claim 1, wherein the sensor is one of a plurality of sensors, each sensor configured to independently read at least one monitorable condition of a corresponding laboratory animal of the plurality of laboratory animals within the group-housed social environment.
  3. The system of claim 1, wherein the sensor is configured to: i) be implanted under skin of the at least one laboratory animal.
  4. The system of claim 1, wherein the transceiver coil of the radiofrequency transceiver is placed in close proximity of a feeder or drinking tube within the container so that the at least one laboratory animal must push against the transceiver coil when feeding or drinking.
  5. The system of claim 4, wherein the feeding or drinking tube is positioned within the container so that the laboratory animal must crawl through the tube when feeding or drinking, thereby keeping said animal in a desired position during a time period required for powering and reading the sensor via the near-field inductive coupling.
  6. The system of any one of claims 1-3, wherein the at least one monitorable condition is selected from the group consisting of: position, gait, posture, temperature, oxygenation, local pH, and the concentration of glucose, lactate, glutamate, histamine, cortisol, NADH, NAD+, cholesterol, xanthine, sarcosine, spermine, glycolate, choline, urate, GABA, lysine, asparate, nicotine, alcohol, ethanol, D-amino acids, 6-hydroxynicotine, oxalate, putrescine, galactose, pyruvate, poly-amines, acyl coenzyme A, glutathione, glycerolphosphate, gamma-glutamyl-putrescine, nucleosides, adenosine, sodium, potassium, and glycine.
  7. The system of any one of claims 1-3, wherein the sensor comprises: a potentiostat, a working electrode, a reference electrode, and a counter electrode.
  8. The system of claim 7, wherein at least one electrochemically active enzyme or ionophore is coated onto at least one of: a top surface of the working electrode, a top surface of the reference electrode, and a top surface of the counter electrode, the at least one electrochemically active enzyme or ionophore selected to detect an ion or biological molecule in the laboratory animal.
  9. The system of claim 8, wherein the at least one electrochemically active enzyme or ionophore comprises glucose oxidase or lactate oxidase, in a glutaraldehyde/bovine serum albumin layer.
  10. The system of claim 9, wherein the glutaraldehyde/bovine serum albumin layer is covered with a filter layer configured to regulate and recycle oxygen required by an enzyme reaction involving the electrochemically active enzyme.
  11. The system of claim 10, wherein the filter layer comprises polyurethane and is configured to improve selectivity of the sensor. by excluding interferent molecules, and wherein the interferent molecules are selected from the group consisting of: acetaminophen, urate, cysteine, bilirubin and ascorbic acid.
  12. The system of any one of claims 1-3, wherein the radiofrequency transmitter is one of a plurality of radiofrequency transmitters, each transmitter of the plurality of radiofrequency transmitters being individually identifiable by a code transmitted to the radiofrequency transceiver.
  13. The system of claim 8, wherein at least one of: the top surface of the working electrode, the top surface of the reference electrode, and the top surface of the counter electrode comprises nanopillars. and the at least one electrochemically active enzyme or ionophore is coated onto the nanopillars, and wherein the least one electrochemically active enzyme or ionophore is an ionophore selected from the group consisting of Na', Ca 2+ , K + , Mg', H', Zn - , Mn 2+ , Cu 2+ , Cl - , PO 4 3- , HPO 4 2- , H 2 PO 4 - , CO 3 2- , HCO 3 - , and OH - .
  14. A method comprising: providing a container configured to contain a plurality of laboratory animals forming a group-housed social environment, the container comprising a radiofrequency transceiver; providing a sensor configured to read at least one monitorable condition of a laboratory animal of the plurality of laboratory animals within the group-based social environment, the sensor configured to be attached to the laboratory animal, the sensor comprising a radiofrequency transmitter, wherein said sensor is of the type powered by on-chip inductive currents and said sensor has a size such to be injectable in the laboratory animal; implanting the sensor under the skin of the laboratory animal; and detecting at least one monitorable condition in the laboratory animal by the radiofrequency transceiver communicating with the radiofrequency transmitter, wherein the at least one radiofrequency transmitter comprises a transmitter coil, the radiofrequency transceiver comprises a transceiver coil, and the radiofrequency transmitter and the radiofrequency transceiver are configured to communicate through near-field inductive coupling between 800 and 900 MHz, wherein the transceiver coil couples to the transmitter coil to power the sensor and a current flow through the transceiver coil induces a corresponding current in the transmitter coil when the transceiver coil and the transmitter coil are critically coupled at a frequency of 800-900 MHz; and wherein the radiofrequency transmitter communicates with the radiofrequency transceiver by reflecting the input power in short pulses, resulting in digital pulse trains comprising a series of changes in reflective power.

Description

CROSS REFERENCE TO RELATED APPLICATIONS The present application claims priority to US Provisional Patent Application No. 62/510,574, filed on May 24, 2017, and US Provisional Patent Application No. 62/548,050, filed on August 21, 2017. STATEMENT OF INTEREST This invention was made with government support under Grant No. HR001 1-15-2-0050 awarded by DARPA. The government has certain rights in the invention. TECHNICAL FIELD The present disclosure relates to monitoring of laboratory animals. More particularly, it relates to a wireless automated animal monitoring system. BRIEF DESCRIPTION OF DRAWINGS The accompanying drawings, which are incorporated into and constitute a part of this specification, illustrate one or more embodiments of the present disclosure and, together with the description of example embodiments, serve to explain the principles and implementations of the disclosure. Fig. 1 illustrates a prior art cage for laboratory animals.Fig. 2 illustrates typical in vitro glucose monitoring results as a function of time.Fig. 3 illustrates location of a feeder in proximity to a drinking tube.Fig. 4 illustrates a tube with reader devices.Fig. 5 illustrates exemplary electrical elements.Fig. 6 illustrates an exemplary sensor with nanopillars.Fig. 7 illustrates a power gain vs frequency plot.Fig. 8 illustrates different sensor types and locations. SUMMARY In a first aspect of the disclosure, a system is described, the system comprising: a container configured to contain at least one laboratory animal, the container comprising at least one radiofrequency transceiver; and at least one sensor configured to read at least one monitorable condition of the at least one laboratory animal, the at least one sensor configured to be attached to the at least one laboratory animal, the at least one sensor comprising at least one radiofrequency transmitter. In a second aspect of the disclosure, a method is described, the method comprising: providing a container configured to contain at least one laboratory animal, the container comprising at least one radiofrequency transceiver; providing at least one sensor configured to read at least one monitorable condition of the at least one laboratory animal, the at least one sensor configured to be attached to the at least one laboratory animal, the at least one sensor comprising at least one radiofrequency transmitter; attaching or implanting the at least one sensor to the at least one laboratory animal; and detecting at least one monitorable condition in the at least one laboratory animal by the at least one radiofrequency transceiver communicating with the at least one radiofrequency transmitter. The present invention relates to a system as defined in the independent claim 1 and a method as defined in the independent claim 14. Preferred embodiments of the invention are defined in the dependent claims. WO2010144494A2 provides a housing system for conducting high throughput animal experiments. The housing system includes a home cage, at least one rotatable turnstile enclosed by housing to form two or more isolation chambers, a means for animal identification, and one or more action stations functionally coupled to one or more isolation chambers. The article VOLK TOBIAS ET AL: "RFID Technology for Continuous Monitoring of Physiological Signals in Small Animals",IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, IEEE SERVICE CENTER, PISCATAWAY, NJ, USA, vol. 62, no. 2, 1 February 2015 (2015-02-01), pages 618-626, describes a low-cost telemetry system based on common radio frequency identification technology optimized for battery-independent operational time, good reusability, and flexibility. Document EP3155899 A1 describes an animal cage including a localization system comprising an animal transceiver and a floor transceiver circuit. The animal transceiver comprises a sensor unit, which is configured to sense a characteristic of the body of the animal. The animal transceiver may be energized by the floor transceiver circuit to perform a measurement by means of the sensor and to transfer the sensor data from the animal transceiver to the floor transceiver circuit. The animal transceiver and the floor transceiver circuit may communicate at different radio frequency ranges, e.g. low frequency (LF) at about 28 to 135 kHz, high frequency (HF) at about 13.56 MHz, and ultra-high frequency (UHF) at 860 to 960 MHz. DETAILED DESCRIPTION The present disclosure describes a cage for laboratory animals that enables monitoring of the state of the animals with a wireless electronic system. This type of cage is referred to as a "smart cage" in the present disclosure. The smart cage enables the continuous or semi-continuous monitoring of laboratory animals for pharmacovigilance through wireless interrogation of the metabolic chemistry of the animals. The capabilities of the smart cage are enabled by the recent development of microscale radiofrequency (RF) tag sensors for measuring metabolites, position an