Chemistry: analytical and immunological testing – Oxygen containing – Carbonyl – ether – aldehyde or ketone containing
Reexamination Certificate
2003-05-20
2004-12-21
Wallenhorst, Maureen M. (Department: 1743)
Chemistry: analytical and immunological testing
Oxygen containing
Carbonyl, ether, aldehyde or ketone containing
C436S164000, C436S172000, C422S068100, C422S082050, C422S082080
Reexamination Certificate
active
06833274
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to sensor devices comprising molecularly imprinted polymers for use in real-time detection of cortisol levels in a fluid sample, and methods for using such devices to detect cortisol levels in real time.
2. Description of the Related Art
Methods and apparatus for the efficient and accurate detection and quantification of cortisol (or hydrocortisone) levels are of particular interest for use in a wide range of applications. For example, because cortisol (a steroid produced in the human body by the adrenal gland) is known to be a regulator of many biological functions, has been identified as a biomarker for many diseases (e.g. Cushing's Syndrome), and has been correlated with levels of stress, the measurement of cortisol in the human body is an important tool for use in clinical diagnostics and in monitoring stress levels during stress-intensive activities.
Presently, applicants have discovered that for many cortisol-detecting applications, the development of portable, non-invasive sensor devices, which are relatively highly-selective and sensitive to the detection of cortisol, and are capable of monitoring cortisol levels in real-time, is of particular interest. For example, there is a military interest in measuring the relative stress levels of soldiers in combat situations. Because cortisol levels in the body tend to fluctuate both throughout the day (cortisol levels tend to be higher in the morning and lower in the evening), and in response to dietary intake and/or metabolic imbalances, it is imperative in combat situations for cortisol measurements to be measured continually and without substantial delay if useful and effective monitoring of the stress and fatigue of a soldier in the field is to be maintained.
Unfortunately, many conventional methods for detecting cortisol levels in the body are incapable of continuous real-time monitoring and/or are highly invasive. For example, a variety of conventional methods for the unambiguous detection of specific cortisol levels in the body require drawing a sample of blood and having the sample processed and analyzed in a laboratory. Much of the technology and laboratory equipment used for such analysis, including gas chromatography-mass spectroscopy (GC-MS) and high performance liquid chromatography (HPLC), are large (not portable), expensive, and/or require sophisticated, often extensive analysis procedures making them undesirable for real-time field analysis. Although these techniques have some degree of sensitivity, they lack specificity, rapid detection, real time analysis, easy operation, low cost, and portability. They also tend to be relatively invasive to the body.
Certain other conventional devices, such as saliva collection kits, are available commercially and are capable of measuring cortisol levels in collected saliva samples. However, such kits are disadvantageous in that they still require lab processing and the time associated therewith.
Recognizing these and other disadvantages and drawbacks associated with conventional sensing methods and apparatus, applicants have developed the present invention.
SUMMARY OF THE INVENTION
The present invention overcomes the aforementioned disadvantages by providing sensor devices that are capable of real-time measurement of cortisol levels in a sample, and also offer the advantages of high selectivity, high sensitivity, easy operation, low cost, and portability. As used herein the term “real-time measurement of cortisol levels” or “real-time” refers to the relatively rapid detection of cortisol levels in a fluid sample freshly produced from a body so as to indicate current or near current cortisol level data for the body. In certain embodiments of the present invention, the real-time measurement of cortisol levels comprises a time delay, from the production of a fresh sample from a human body, for example, via salivation, expectoration, urination, and the like, to the detection of the cortisol levels in the produced sample, of about 15 minutes or less. Preferably, the time delay is about 5 minutes or less, and more preferably 1 minute or less. In certain other embodiments, the “real-time measurement” can be obtained with substantially no delay.
Applicants have discovered that molecularly imprinted polymers (MIPs) capable of binding with cortisol molecules can be used to great advantage in sensor devices designed to detect varying levels of cortisol in the human body in real-time. In particular, applicants have discovered that MIPs according to the present invention can be advantageously adapted for use with a wide variety of light sources and detectors to produce cortisol sensor devices which are able to detect cortisol molecules with a relatively high degree of selectivity and sensitivity, and in less time and with fewer false positives than conventional optical sensors. In addition, applicants have discovered that the MIPs of the present invention can be incorporated in low-cost, portable devices capable of being used in the field to provide real-time measurements of cortisol levels in the human body.
According to one aspect of the present invention, provided are sensor devices for detecting cortisol molecules. In certain preferred embodiments, the sensor devices of the present invention comprise a molecularly imprinted polymer comprising a cortisol-binding chromophore operatively associated with a source of excitation energy for the chromophore; and a detector for detecting fluorescent energy emitted upon chromophore excitation.
According to certain other aspects of the present invention, provided are methods of detecting cortisol molecules in real-time by using a sensor device of the present invention.
REFERENCES:
patent: 5372719 (1994-12-01), Afeyan
patent: 5453199 (1995-09-01), Afeyan
patent: 5641539 (1997-06-01), Afeyan
patent: 5821311 (1998-10-01), Mosbach
patent: 5858296 (1999-01-01), Domb
patent: 5872198 (1999-02-01), Mosbach
patent: 5959050 (1999-09-01), Mosbach
patent: 5994110 (1999-11-01), Mosbach
patent: 6051372 (2000-04-01), Bayerl
patent: 6127154 (2000-10-01), Mosbach
patent: 6177513 (2001-01-01), Takeuchi et al.
patent: 6212959 (2001-04-01), Perkins
patent: 6255461 (2001-07-01), Mosbach et al.
patent: 6458599 (2002-10-01), Huang
patent: 2002/0090664 (2002-07-01), Wiegand et al.
patent: 2002/0092858 (2002-07-01), Bowman
patent: 2003/0129092 (2003-07-01), Murray
patent: 11019076 (1997-07-01), None
patent: 11023579 (1997-07-01), None
patent: 11038004 (1997-07-01), None
patent: 11326318 (1998-05-01), None
patent: 2000275248 (2000-06-01), None
patent: 01/77672 (2001-01-01), None
patent: 01/86263 (2001-11-01), None
Baggiani et al. Talanta, vol. 51, 2000, pp. 71-75.*
Sreenivasan et al. Journal of Applied Polymer Science, vol. 71, 1999, pp. 1823-1826.*
Kriz et al. Analytical Chemistry, vol. 67, 1995, pp. 2142-2144.*
Sreenivasan. Journal of Applied Polymer Science, vol. 82, 2001, pp. 889-893.*
Sreenivasan. Journal of Polymer Research, vol. 8, No. 3, Sep. 2001, pp. 197-200.*
Cameron Alexander, Craig R. Smith, Michael J. Whitcombe, and Evgeny N. Vulfson, “Imprinted Polymers as Protecting Groups for Regioselective Modification of Polyfunctional Substrates”, J. Am. Chem. Soc. 1999, 121, 6640-6651. [Contains chemistry and schematic for steroid-selective MIP.].
Akimitsu Kugimiya, Toshifumi Takeuchi, “Surface Plasmon Resonance Sensor Using Molecularly Imprinted Polymer for Detection of Sialic Acid” Biosensors & Bioelectronics 16 (2001) 1059-1062.
Jun Matsui, Miho Higashi, and Toshifumi Takeuchi, “Molecularly Imprinted Polymer as 9-Ethyladenine Receptor Having a Porphyrin-Based Recognition Center” J. Am. Chem. Soc. 2000, 122,5128-5219.
Lawrence David S.
Sample Jennifer L.
Cooch Francis A.
The Johns Hopkins University
Wallenhorst Maureen M.
LandOfFree
Cortisol sensor does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cortisol sensor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cortisol sensor will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3314576