Systems and Methods for Monitoring Chemical and Biological Activity using Differential Measurements

Abstract

A system operable to monitoring bio / chemical activities includes a first measurement probe, a second measurement probe and a comparator. The first measurement probe is operable to interrogate one or more physical properties of a sample at a first location of the sample, and to output, in response, a first measurement signal. The second measurement probe is operable to interrogate one or more physical properties of the sample at a second location of the sample, and to output, in response, a second measurement signal. The comparator is coupled to receive the first and second measurement signals, the comparator configured to output a difference signal comprising the difference between the first and second measurement signals, the difference signal corresponding to the difference in one or more bio / chemical activities occurring at the first location of the sample relative to the second location of the sample.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This is a continuation-in-part of prior U.S. patent application Ser. No. 10 / 064,392, filed Jul. 9, 2002, which claims the benefit of U.S. Provisional Application No. 60 / 375,668, filed Apr. 26, 2002, each application herein incorporated by reference in its entirety for all purposes.BACKGROUND[0002]Biologic systems and complex chemical processes, such as biochemical pathways, cellular activities, synthetic organic processes, and molecular interactions (collectively referred to bio / chemical activity herein) pose considerable challenges to scientists interested in directly monitoring activities. Such systems usually are rather complex, existing in environments where a number of differing activities are occurring simultaneously, and are thus noisy. Currently, there are a number of general techniques routinely used for detecting biochemical phenomena [David Freifelder, Physical Biochemistry, 1982, second edition, W. H. Freeman & Co., New York],...

AI Technical Summary

Benefits of technology

The present invention provides systems and methods for monitoring biological and chemical activities using differential measurements. These systems can be used in a wide range of applications, from large-scale industrial monitoring to ultra-small microfluidic process monitoring and detection. The system includes a first measurement probe, a second measurement probe, and a comparator. The first measurement probe interrogates one or more physical properties of a sample at a first location and outputs a first measurement signal. The second measurement probe interrogates one or more physical properties of the sample at a second location and outputs a second measurement signal. The comparator receives the first and second measurement signals and outputs a difference signal, which is the difference between the first and second measurement signals. This difference signal corresponds to the difference in bio / chemical activities occurring at the first location of the sample relative to the second location of the sample.

Problems solved by technology

Biologic systems and complex chemical processes, such as biochemical pathways, cellular activities, synthetic organic processes, and molecular interactions (collectively referred to bio / chemical activity herein) pose considerable challenges to scientists interested in directly monitoring activities.

Such systems usually are rather complex, existing in environments where a number of differing activities are occurring simultaneously, and are thus noisy.

A very limited number of techniques utilize the measurement of properties which directly measure some physiologic property of a system, or do not require the attachment of a label.

However, in these cases, only a very limited amount of information is available, and in most cases, the techniques are difficult to carry out, and thus the throughput is extremely limited.

This poses many problems for the general application of these techniques to chemical and biologic systems, as there often is a high level of inherent noise, and small changes due do specific chemical or biologic activities are therefore not detectable.

Small changes in ambient temperature produce changes in the electrical properties of the system being studied, thus rendering the signal effectively undetectable.

Another relevant example is the detection of s specific activity in a complex mixture, such as a suspension of biologic cells or tissues; there are multiple activities on-going at any given time, so the detection of a specific activity is very challenging, at least if its signal is not easily separated from all of the other signals in the system.

Each of the above-mentioned approaches has limitations.

In systems where some form of amplification needs to take place, the added burden of incorporating a mechanism for amplification is time consuming, incurs costs, and in many cases is not possible.

In cases where ultra-sensitive measurement systems are used, there are often considerable costs, and often the size and throughput of the system makes it unsuitable for many applications.

Thus, although electronic detection has found utility in biological, chemical, medical, and industrial applications, there exist significant limitations which prevent larger utility.

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