Compact apparatus for noninvasive measurement of glucose through near-infrared spectroscopy

Abstract

The invention involves the monitoring of a biological parameter through a compact analyzer. The preferred apparatus is a spectrometer based system that is attached continuously or semi-continuously to a human subject and collects spectral measurements that are used to determine a biological parameter in the sampled tissue. The preferred target analyte is glucose. The preferred analyzer is a near-IR based glucose analyzer for determining the glucose concentration in the body.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 10 / 472,856 filed Mar. 3, 2003, which claims: [0002] priority to PCT application no. PCT / US03 / 07065 filed Mar. 3, 2003, which claims benefit of U.S. provisional patent application No. 60 / 362,885, filed on Mar. 8, 2002; [0003] benefit of U.S. provisional patent application No. 60 / 362,899, filed on Mar. 8, 2002; and [0004] benefit of U.S. provisional patent application No. 60 / 448,840 filed on Feb. 19, 2003; [0005] each of which is incorporated by its entirety by this reference thereto.BACKGROUND OF THE INVENTION [0006] 1. Field of the Invention [0007] This invention relates generally to the noninvasive measurement of biological parameters through near-infrared spectroscopy. In particular, an apparatus and a method are disclosed for noninvasively, and continuously or semi-continuously, monitoring a biological parameter, such as glucose in tissue. [0008] 2. Discussion of ...

AI Technical Summary

Problems solved by technology

Diabetes is a chronic disease that results in improper production and use of insulin, a hormone that facilitates glucose uptake into cells.

Diabetes is a leading cause of death and disability worldwide.

However, current monitoring techniques discourage regular use due to the inconvenient and painful nature of drawing blood through the skin prior to analysis (The Diabetes Control and Complication Trial Research Group, “The effect of intensive treatment of diabetes on the development and progression of long-term complications of insulin-dependent diabetes mellitus”, N. Engl. J. Med., 329, 1993, 997-1036).

Unfortunately, recent reports indicate that even periodic measurement of glucose by individuals with diabetes, (e.g. seven times per day) is insufficient to detect important glucose fluctuations and properly manage the disease.

In addition, nocturnal monitoring of glucose levels is of significant value but is difficult to perform due to the state of existing technology.

Obviously, this form of alternative invasive glucose determination may not be used to collect venous or arterial blood for analysis, but may be used to collect capillary blood samples.

However, some of the techniques can be applied to the skin in a fashion that draws blood.

This leads to samples being collected with varying analyte and interferent concentrations.

Another example is that a laser poration method can result in blood droplets.

Conversely, devices such as a lancet, applied current, laser poration, or suction are referred to as either a traditional invasive or alternative invasive technique as they do not fulfill both the three hour and penetration of skin parameters.

First, at least part of the device penetrates the skin.

Consequently, the limitations of the device include the potential for significant skin irritation, collection of a biohazard, and a limit of three readings per hour.

A common issue with semi-implantable and implantable devices is coating by proteins.

Inherent in these approaches are health risks due to the sensor implantation, infections, patient inconvenience, and measurement delay.

Notably, none of these technologies are noninvasive.

Further, none of these technologies offer continuous glucose determination.

One interference to a determination of blood / tissue glucose concentration measured indirectly is a rapid change in blood perfusion, which also leads to fluid movement between the compartments.

This type of physiological change interferes constructively or destructively with the analyte signal of the indirect measurement.

While methods for preprocessing effectively compensate for variation related to instrument and physical changes in the sample and enhance the net analyte signal in the presence of noise and interference, they are often inadequate for compensating for the sources of tissue related variation.

For example, the highly nonlinear effects related sampling different tissue locations can't be effectively compensated for through a pathlength correction because the sample is multi-layered and heterogeneous.

In addition, fundamental assumptions inherent in these methods, such as the constancy of multiplicative and additive effects across the spectral range and homoscadasticity of noise are violated in the non-invasive tissue application.

Meters with increased error such as 10% are acceptable, though the error of the device being calibrated may increase.

Currently, no device using near-infrared spectroscopy for the noninvasive measurement of glucose has been approved for use by persons with diabetes due to technology limitations that include poor sensitivity, sampling problems, time lag, calibration bias, long-term reproducibility, stability, and instrument noise.

Fundamentally, however, accurate noninvasive estimation of blood glucose is presently limited by the available near-infrared technology, the trace concentration of glucose relative to other constituents, and the dynamic nature of the skin and living tissue of the patient.

Further limitations to commercialization include a poor form factor (large size, heavy weight, and no or poor portability) and usability.

For example, existing near-infrared technology is limited to larger devices that do not provide (nearly) continuous or automated measurement of glucose and are difficult for consumers to operate.

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