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Methods and systems for assessing biological material using optical detection techniques

a biological material and optical detection technology, applied in the field of optical or spectroscopic detection, can solve the problems of insufficient high throughput screening of biological materials, inability to accurately predict the response and side effects observed in human clinical trials, and inability to scale up to provide the high throughput screening necessary to test the numerous candidate compounds generated by traditional and computational means. , to achieve the effect of high throughpu

Inactive Publication Date: 2005-06-02
CYTOSCAN SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0019] Observation and interpretation of geometrical and / or intrinsic optical properties of individual cells or cell populations is achieved in both in vitro and in vivo systems without altering characteristics of the sample by applying physiologically invasive materials, such as fixatives. Physiologically non-invasive contrast enhancing agents, such as vital dyes, may be used in desired applications to enhance the sensitivity of optical detection techniques. In applications employing contrast enhancing agents, the optical detection techniques are used to assess extrinsic optical properties of the biological materials.

Problems solved by technology

Screening methods currently used are generally difficult to scale up to provide the high throughput screening necessary to test the numerous candidate compounds generated by traditional and computational means.
Moreover, studies involving cell culture systems and animal model responses frequently don't accurately predict the responses and side effects observed during human clinical trials.
Conventional methods for assessing the effects of various agents or physiological activities on biological materials, in both in vitro and in vivo systems, generally are not highly sensitive or informative.
Cytotoxicity assays generally do not provide any information relating to the cause(s) or time course of cell death.
This type of assay provides useful information, but it does not provide information relating to the mechanism of action, the effect on other metabolites or metabolic functions, the time course of the physiological effect, general cell or tissue health, or the like.
The technique employed by Ts'o et al. would not be practical for human clinical use, since imaging of intrinsic signals was achieved by implanting a stainless steel optical chamber in the skull of a monkey and contacting the cortical tissue with an optical oil.

Method used

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  • Methods and systems for assessing biological material using optical detection techniques
  • Methods and systems for assessing biological material using optical detection techniques
  • Methods and systems for assessing biological material using optical detection techniques

Examples

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example 1

[0100] Sprague-Dawley rats (male and female; 25 to 35 days old) were prepared as described in Aghajanian, A. K. and Rasmussen, K., Synapse 31:331, 1989; and Buckmaster, P. S., Strowbridge, B. W., Schwartzdroin, P. A., J. Neurophysiol. 70:1281, 1993. In most hippocampal slice experiments, simultaneous extracellular field electrode recordings were obtained from CA1 and CA3 areas. For stimulation-evoked afterdischarge (13 slices, 8 animals), the concentration of Mg2+ in the bathing medium was reduced to 0.9 mM. A bipolar tungsten stimulating electrode was placed on the Schaffer collaterals to evoke synaptically driven field responses in CA1; stimuli consisted to 100 to 300-μs-duration pulses at an intensity of four times population-spike threshold. Afterdischarges were evoked by a 2-s train of such stimuli delivered at 60 Hz. Spontaneous interictal-like bursts were observed in slices treated with the following modifications or additions to the bathing medium: 10 mM K+ (6 slices; 4 anim...

example 2

[0105] This example illustrates optical changes indicative of neuronal activity in a human subject by direct cortical electrical stimulation. Surface electrical recordings (surface EEG, ECOG) were correlated with optical changes. Intrinsic optical changes were evoked in an awake patient during stimulating-electrode “calibration.” Four stimulation trials were sequentially applied to the cortical surface, each stimulation evoking an epileptiform afterdischarge episode. A stimulation trial consisted of: (1) monitoring resting cortical activity by observing the output of the recording electrodes for a brief period of time; (2) applying an electric current via the stimulation-electrodes to the cortical surface at a particular current for several seconds; and (3) monitoring the output of the recording electrodes for a period of time after stimulation has ceased.

[0106] The cortex was evenly illuminated by a fiber optic emr passing through a beam splitter, controlled by a D.C. regulated po...

example 3

[0117] Stimulation mapping of the cortical surface was performed on awake human patients under local anesthesia to identify sensory / motor cortex and Broca's areas. The illumination source and optical detection device and processing techniques used were the same as those described in Example 2. During three “tongue wiggling” trials, images were averaged (32 frames, 1 sec) and stored every 2 seconds. A tongue wiggling trial consisted of acquiring 5-6 images during rest, then acquiring images during the 40 seconds that the patient was required to wiggle his tongue against the roof of his mouth, and then to continue acquiring images during a recovery period. The same patient was then required to engage in a “language naming” trial. A language naming trial consisted of acquiring 5-8 images during rest (control images—the patient silently viewing a series of blank slides), then acquiring images during the period of time that the patient engaged in the naming paradigm (naming a series of o...

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Abstract

Optical detection techniques for the assessment of the physiological state, health and / or viability of biological materials are provided. Biological materials which may be examined using such techniques include cells, tissues, organs and subcellular components. The inventive techniques may be employed in high throughput screening of potential diagnostic and / or therapeutic agents.

Description

REFERENCE TO PRIORITY APPLICATIONS [0001] This application is a divisional application of U.S. patent application Ser. No. 09 / 326,244, filed Jun. 4, 1999, issuing as U.S. Pat. No. 6,834,238 on Dec. 21, 2004, which claims priority from U.S. Provisional Patent Application No. 60 / 088,494, filed Jun. 8, 1998, entitled METHODS AND APPARATUS FOR ASSESSING BIOLOGICAL MATERIALS USING OPTICAL DETECTION TECHNIQUES, which are hereby incorporated herein by reference.FIELD OF THE INVENTION [0002] The methods and systems of the present invention employ optical, or spectroscopic, detection techniques for assessing the health, physiological condition, and viability of biological materials such as tissues, cells, and subcellular components, and may be used in both in vitro and in vivo systems. One important application of the methods and apparatus of the present invention is high throughput screening of candidate agents and conditions to evaluate their suitability as diagnostic or therapeutic agents...

Claims

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Application Information

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IPC IPC(8): A61K31/00A61K31/635A61K45/06
CPCA61K31/00A61K31/635A61K45/06A61K2300/00
Inventor HOCHMAN, DARYL W.
Owner CYTOSCAN SCI
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