Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
2000-08-28
2001-10-30
Lacyk, John P. (Department: 3736)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S345000, C600S365000, C600S573000
Reexamination Certificate
active
06309351
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to continual measurement of indicia of the physiological state of a subject, and particularly to continual measurement of analytes in tissues and body fluids of a subject.
BACKGROUND OF THE INVENTION
The physiologic state of a subject can by monitored by measurement of certain indicia.
Some such indicia, including the familiar “vital signs” such as the subject's body temperature, heart rate, respiratory rate, and the like can be measured directly either without resort to instrumentation, or by use of simple instruments placed onto a body surface or within a body cavity. Body temperature measurement, for example, can be made directly by use of a thermometer or thermistor placed on the skin or within a body cavity. Other indicia of physiologic state that can be measured directly require the use of more complex instrumentation. Such indicia include electrocardiography and electroencephalography, for example, and the instrumentation for measuring such indicia may include apparatus affixed to the subject's skin or implanted within the body.
Biochemical indicia of a subject's physiologic state can provide highly useful information. Such biochemical indicia include the presence and amounts in the subject's tissue or body fluids of certain chemical species; by way of example, such chemical species may be or may have been ingested by or administered to the subject, or they may be metabolic products or byproducts or metabolic precursors, or they may constitute parts of the subject's metabolic apparatus, such as enzymes and hormones and the like. Thus, the presence or amount of a drug or drug metabolite, for example in a sample of a subject's blood or urine, can provide an indication of the subject's history of use of the drug, or can provide an assurance that a dosage or route of administration is providing a suitable therapeutic level in the subject's tissues. And, as a well-known example, a measure of the amount of glucose in a subject's blood, or of ketones in the subject's urine, can provide useful information for management of hypoglycemia and hyperglycemia, particularly in diabetics.
Such biochemical indicia can be measured, for example, in a sample of a fluid or tissue removed from the subject's body; blood work and urinalysis, routine or more complete, for example, can provide information regarding such indicia. Where the subject's physiologic state may change significantly over short periods of time, samples for analysis of biochemical indicia may be taken more frequently.
For some physiologic conditions the time scale for changes in the physiologic state can be short, so that removal and analysis of the appropriate sample at a preferred frequency is impractical. It is generally understood, for example, that more frequent sampling and analysis of a diabetic person's blood glucose, together with careful management of the person's sugar and insulin, can provide an improvement in quality of life and the lifespan of the diabetic; but removal of the blood sample is painful, and the apparatus surrounding the analysis of the sample is cumbersome and inconvenient to use.
For some types of biochemical indicia, then, there is a need for methods for “continual” monitoring, that is to say, for measuring the biochemical indicia over extended monitoring time periods (for example, around the clock; or 24 hours per day throughout the week; etc.) substantially without interruption, or in a continuing series of measurements at appropriately spaced intervals.
In some instances detectors may be available to directly detect the biochemical indicia in the range of concentrations that are pertinent to monitoring the physiologic state of the subject. In these instances, the detector may be implanted and left to reside within the tissue or internal body space, where the detector measures the biochemical analyte as it comes within detectable range of the detector, and records or transmits the resulting data for further use.
In other instances the biochemical indicia may not be directly detectable by known detectors. In these instances some treatment of the analyte is required as a step preliminary to detection. Such treatment may, for example, result in the analyte (or the analyte together with some other substance involved in the treatment) having a particular spectrum of radiation absorption (detectable for example colorimetrically) or of radiation (detectable for example by fluorescence detection). Or, the treatment may entail a specific chemical reaction (as for example by a substrate-specific catalyst such as an enzyme) that results in generation of a chemical species (for example an ion) that is directly detectable using a known detector.
Where some treatment of the analyte is required, a reservoir may be employed for collecting the analyte and carrying out the treatment. Such a reservoir can be held in operational proximity to (in some instances in contact with) the detector and within or in contact with a tissue or surface of the body of the subject to be monitored. Conveniently, the reservoir can for example be placed on the subject's skin; in this instance the analyte passes into the reservoir through the skin surface (the movement can be facilitated by a potential gradient), where it undergoes the treatment and is then detected.
Irrespective of the technique of detections where the analyte is continually collected, it can accumulate in the reservoir, resulting in a progressively higher measurement over time, resulting in decreased reliability in subsequent measurements over the monitoring period.
SUMMARY OF THE INVENTION
In one general aspect the invention features a method for continual monitoring of a physiologic analyte in a subject, by contacting the subject with a collection reservoir such that the analyte can move from the subject into the collection reservoir, the collection reservoir being in contact with a detector, collecting the analyte in the collection reservoir, using the detector to detect the analyte in the collection reservoir, and, once detection of the analyte is accomplaished, rendering the analyte undetectable by the detector.
In some embodiments the analyte itself is not directly detected by the detector, but is instead processed through a detection cascade, the final step of which occurs at the detector. In such embodiments the step of using the detector to detect the analyte includes steps of treating the analyte to generate a detectable signal or a detectable chemical species that is detected by the detector. In some embodiments the step of treating the analyte includes contacting the analyte with a catalyst, such as an enzyme, that reacts with the analyte to produce a detectable chemical species; in preferred such embodiments the reaction of the catalyst and the enzyme further results in conversion of the analyte to a reaction product that is not detected by the detector (that is, the reaction product is removed from the detection cascade); and in preferred such embodiments the detection of the detectable chemical species by the detector results in conversion of the detectable chemical species to a reaction product that is not detected by the detector.
As a result, whether the analyte is detected directly by the detector, or is instead detected indirectly by being treated in a cascade of reactions resulting in a detectable signal or detectable chemical species which is detected by the detector, the potential for detection of each analyte molecule is extinguished once detection occurs. As a significant consequence, there is no accumulation, over the monitoring time period, of detectable signal or of detectable chemical species or of the analyte itself once detection has occurred. For any measurement at any time during the monitoring time, only that detectable analyte or detectable signal which has entered the collection reservoir since the previous measurement, or that detectable signal or detectable chemical species that has been produced since th
Kurnik Ronald T.
Potts Russell Owen
Tamada Janet
Tierney Michael
Carter Ryan
Cygnus Inc.
Lacyk John P.
McClung Barbara
Robins & Pasternak LLP
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