Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reissue Patent
2002-10-23
2004-06-08
Winakur, Eric F. (Department: 3736)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S310000, C422S082070, C436S501000
Reissue Patent
active
RE038525
ABSTRACT:
The present invention relates to a sensor for use in the measurement or monitoring of analytes in subcutaneous fluid using optical techniques and to an analyte monitoring system using this sensor. The sensor is particularly suitable for use in situations in which analyte levels must be closely monitored, for example with drugs that must be maintained within a narrow therapeutic window or where analyte measurements must be taken repeatedly, such as in long term diabetes.
In the management of diabetes, the regular measurement of glucose in the blood is essential in order to ensure correct insulin dosing. Furthermore, it has been demonstrated that in the long term care of the diabetic patient better control of blood glucose levels can delay, if not prevent, the onset of retinopathy, circulatory problems and other degenerative diseases often associated with diabetes. Thus there is a need for reliable and accurate self-monitoring of blood glucose levels by diabetic patients.
Currently, blood glucose is monitored by diabetic patients with the use of commercially available colorimetric test strips or electrochemical biosensors (e.g. enzyme electrodes), both of which require the regular use of a lancet-type instrument to withdraw a suitable amount of blood each time a measurement is made. On average, the majority of diabetic patients would use such instruments to take a measurement of blood glucose twice a day. However, the US National Institutes of Health recently recommended that blood glucose testing should be carried out at least four times a day, a recommendation that has been endorsed by the American Diabetes Association. This increase in the frequency of blood glucose testing imposes a considerable burden on the diabetic patient, both in terms of financial cost and in terms of pain and discomfort, particularly in the long term diabetic who has to make regular use of a lancet to draw blood from the fingertips. Thus, there is clearly a need for a better long term glucose monitoring system that does not involve drawing blood from the patient.
There have been a number of recent proposals for glucose measurement techniques that do not require blood to be withdrawn from the patient. Various attempts have been made to construct devices in which an enzyme electrode biosensor is placed on the end of a needle or catheter which is inserted into a blood vessel (Wilkins E and Atanasov P, Med. Eng. Phys (1996) 18: 273-288). Whilst the sensing device itself is located within a blood vessel, the needle or catheter retains connection to the external environment. In practice, such devices are not suitable for use in human patients firstly because the insertion of a needle or catheter into a blood vessel poses an infection risk and is also uncomfortable for the patient and hence not suitable for continuous use. Secondly, devices of this type have not gained approval for use in human patients because it has been suggested that the device itself, on the end of a needle or catheter, may be responsible for the shedding of thromboses into the patient's circulation. This obviously poses a very serious risk to the patient's health.
Mansouri and Schultz (Biotechnology 1984), Meadows and Schultz (Anal. Chim. Acta. (1993) 280: pp 21-30) and U.S. Pat. No. 4,344,438 all describe devices for the in situ monitoring of low molecular weight compounds in the blood by optical means. These devices are designed to be inserted into a blood vessel or placed subcutaneously but require fibre-optic connection to an external light source and an external detector. Again the location of these devices in a blood vessel carries an associated risk of promoting thromboses and in addition, in one embodiment the need to retain a fibre-optic connection to the external environment is impractical for long term use and carries a risk of infection.
In the search for a less invasive glucose monitoring technique some attention has also been focused on the use of infra-red spectroscopy to directly measure blood glucose concentration in blood vessels in tissues such as the ear lobe or finger tip which are relatively ‘light transparent’ and have blood vessels sited close to the surface of the skin (Jaremko J and Rorstad O, Diabetes Care 1998 21:, 444-450 and Fogt E J, Clin. Chem. (1990) 36:, 1573-80) This approach is obviously minimally invasive, but has proven to be of little practical value due to the fact that the infra-red spectrum of glucose in blood is so similar to that of the surrounding tissue that in practical terms it is virtually impossible to resolve the two spectra.
It has been observed that the concentration of analytes in subcutaneous fluid correlates with the concentration of said analytes in the blood, consequently there have been several reports of the use of glucose monitoring devices which are sited in a subcutaneous location. In particular, Atanasov et al. (Med. Eng. Phys. (1996) 18: pp 632-640) describe the use of an implantable glucose sensing device (dimensions 5.0×7.0×1.5 cm) to monitor glucose in the subcutaneous fluid of a dog. The device consists of an amperometric glucose sensor, a miniature potentiostat, an FM signal transmitter and a power supply and can be interrogated remotely, via antenna and receiver linked to a computer-based data acquisition system, with no need for a connection to the external environment. However, the large dimensions of this device would obviously make it impractical for use in a human patient.
In WO 91/09312 a subcutaneous method and device is described that employs an affinity assay for glucose that is interrogated remotely by optical means. In WO 97/19188 a further example of an implantable assay system for glucose is described which produces an optical signal that can be read remotely. The devices described in WO 91/09312 and WO 97/19188 will persist in the body for extended periods after the assay chemistry has failed to operate correctly and this is a major disadvantage for chronic applications. Removal of the devices will require a surgical procedure.
There remains a clear need for sensitive and accurate blood glucose monitoring techniques which do not require the regular withdrawal of blood from the patient, which do not carry a risk of infection or discomfort and which do not suffer from the practical disadvantages of the previously described implantable devices.
Accordingly, in a first aspect the present invention provides a sensor for the detection or quantitative measurement of an analyte in subcutaneous fluid, the sensor being characterised in that it can function in a subcutaneous location with no physical connection to the external environment, said sensor incorporating an assay for said analyte the readout of which is a detectable or measurable optical signal, which optical signal can, when the sensor is in operation in a subcutaneous location, be interrogated transcutaneously by external optical means and said sensor being biodegradable or hydrolysable in vivo.
The sensor of the invention incorporates assay means for detecting an analyte or for measuring the amount of an analyte, the readout of the assay being an optical signal. Because the sensor is located just under the skin, an optical signal generated in the sensor can be detected transcutaneously (i.e. through the skin) thus obviating the need for any direct connection between the sensor and the external environment. Once the sensor is in place in a subcutaneous location analyte measurements can be taken as often as is necessary with no adverse effects. This is a particular advantage in relation to the long term care of diabetic patients because if glucose measurements are taken more frequently, tighter control can be maintained over the level of glucose in the blood and the risk of developing conditions related to poorly regulated blood glucose, such as retinopathy, arthritis and poor circulation, will be reduced.
Because the sensor of the invention does not itself contain any of the optical components required to interrogate the readout of the assay (these being provided separately and
Stanley Christopher John
Weber Anders
Nixon & Vanderhye P.C.
Torsana Diabetes Diagnostics A/S
Winakur Eric F.
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