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Electrochemical Methods, Sensors and Instruments for Immunology

#2132


The Study and Development of Electrochemical Methods, Sensors and Instruments for Evaluation of the Microelemental and Immune Status of Organisms

Tech Area / Field

  • MED-DID/Diagnostics & Devices/Medicine
  • BIO-CHM/Biochemistry/Biotechnology
  • CHE-ANL/Analytical Chemistry/Chemistry
  • INS-MEA/Measuring Instruments/Instrumentation

Status
8 Project completed

Registration date
27.03.2001

Completion date
20.04.2007

Senior Project Manager
Kulikov G G

Leading Institute
VNIITF, Russia, Chelyabinsk reg., Snezhinsk

Supporting institutes

  • Ural State Economic University, Russia, Sverdlovsk reg., Ekaterinburg

Collaborators

  • Universidad Complutense de Madrid, Spain, Madrid\nIreland's Information and Communication Technologies Research Center/University College, Lee Maltings, Ireland, Cork\nQueen Mary, University of London / Interdisciplinary Centre in Biomedical Materials, UK, London\nRENAL Research Institute, USA, New York\nTulane University Medical Center / Energy Spatial Analysis Research Laboratory, USA, LA, New Orleans\nLawrence Livermore National Laboratory, USA, CA, Livermore\nUniversity of Massachusetts Lowell, USA, MA, Lowell\nErnst Moritz Arndt Universitat Greifswald / Institut fur Chemie und Biochemie, Germany, Greifswald\nUniversidade de Coimbra, Portugal, Coimbra

Project summary

Health of people, early diagnosis of hazardous diseases, determination of factors favoring development of diseases in the human organism, and ascertaining the effect of toxicants on appearance and the course of diseases represent very topical problems of today. Health of people depends, along with other factors, on the state of the immune system of the human organism, balance or unbalance of the microelemental composition, the antioxidant condition, presence of pathogenic pollutants in the environment, and early diagnosis of diseases.

It is known that extracellular fluids contain low-molecular antioxidants, which are deeply involved in mechanisms protecting against active oxygen compounds. The antioxidant action of these compounds is explained by their ability to capture oxygen radicals. The ability of extracellular antioxidants to bind free carbon radicals (C-radicals) is less known.

Methods used to evaluate the antioxidant performance are complex, expensive, time consuming and, generally, inapplicable to continuous monitoring.

The redox potential could be used as a general nonselective parameter for assessing the antioxidant status of an organism. However, the existing methods fail to evaluate the redox potential of such complicated systems as fluids in an organism, because the redox condition is determined by some irreversible redox reactions.

These reactions involve perse low- and high-molecular compounds and free radicals. It is possible to distinguish two main series of redox reactions by which ascorbic acid and differently structured thiols are oxidized. Considering the modern state of electrochemical and biosensor technologies, for the foreseeable future one can hardly expect the advent of a multisensor providing a selective response to numerous reactions of free radicals, thiol-containing proteins, low-molecular thiols, enzymes, and other compounds. Therefore we think it reasonable to solve this complicated task step by step. To this end:

– examine and select some mediator systems having potential regions, in which certain substances that determine the antioxidant status of an organism would be reactive. After the group analysis it would be possible to proceed to development of real-time monitoring schemes;


– select transducers and methods suitable for immobilization of mediator systems on the transducer surface;
– select methods for generation and recording of responses;
– develop simple cheap hand-held instruments based on sensors including chosen mediator systems.

By solving the aforementioned problems, it will be possible to quickly obtain important medical information.

The man's health, including his immune system, depends directly on such factor as the microelemental balance or unbalance.

Diseases, syndromes and pathologic conditions, which are caused by the excess, deficit or unbalance of microelements in the human organism, have long been known in clinical medicine (for example, endemic goiter, iron deficiency anemia, poisoning with some metals, etc.). However, the overwhelming majority of those malfunctions were not registered because of the scarcity (lack) or complexity of control means. As a result of vigorous industrial development, the global technogenic pollution of the environment forces out purely natural forms of pathology of all living creatures and distorts those forms.

Today researchers have focussed on a factor, which is thought to be significant for aetiology of many diseases, namely the disturbance of the microelemental balance. Accumulation of valuable, yet poorly systematized facts have made it necessary to set out a new science of microelementoses as a special section of pathology whose subject is a new class of human diseases having known aetiology but yet unclear pathogenesis. It has become quite obvious that to make a correct diagnosis and prescribe an effective treatment, a modern practicing physician should, in the first place, evaluate the balance of microelements in the patient's organism.

Unfortunately, analysis methods that can provide information about the concentration of microelements in the human organism either have a low sensitivity (below the deficiency level of elements) or require special expensive equipment, which is available at a few medical centres. Practising physicians have little access to equipment for diagnosis of pathological conditions caused by unbalance or deficit of microelements in the human organism. Clinicists refer to the analysis only if they suspect the iron deficiency condition or when an organism was exposed to strongly toxic microelements. However, some microelements, e.g. cadmium and lead, which have long been considered as toxic, possess properties of essential (indispensable) (A substance is referred to as indispensable for a living organism if this organism can neither grow nor finish its life cycle in the absence of this substance) elements. Patients having various forms of microelemental deficit are very large in number.

The task consists in development of simple equipment and an automatic efficient method for evaluating the microelemental status of the human organism, including determination of some microelements in biological liquids and tissues at the levels that correspond to the deficit and the excess of an element in the human organism.

To solve the task concerning the evaluation of the microelemental status of an organism, it is necessary to develop inexpensive, simple, sensitive and rapid diagnosis methods and instruments supporting such methods. Electrochemical methods of analysis show great promise with respect to solution of the aforementioned tasks. This statement is confirmed by high sensitivity and selectivity of electrochemical methods, simplicity of the hardware, the use in laboratory and field conditions, the possibility of creating portable instruments, and a low cost of analysis compared to other methods.

The goal of the Project: Create electrochemical sensors and instruments for evaluating the microelemental status of the human organism, including measurement of concentrations of vital microelements in biological liquids, and for assessing the immune status of the human organism, including determination of the redox and thioldisulfide (TDS) status of the human organism.

Specific goals of the Project include development of:

– A solid-phase electrochemical sensor with a mediator function for evaluation of the redox potential of biological liquids in the human organism.

– A solid-phase electrochemical sensor for determination of the TDS status of the human organism.

– Solid-phase sensors capable of operating in turbid protein-rich liquids for determination of microconcentrations of Cu, Pb, Cd, Zn, Ni, and Se used to evaluate the microelemental status of the human organism.

– New stripping voltammetric methods for determination of copper, zinc, lead, cadmium, selenium, and nickel concentrations corresponding to the deficit of the elements in the human organism used to assess the redox potential and TDS.

– Algorithms, programs and portable instruments for operation in conjunction with the aforementioned sensors:

– a portable computerized instrument for determination of the redox (including thioldisulfide) balance used to assess the immune status of the human organism (Instrument 1);
– a portable computerized instrument for determination of the microelemental composition of biological liquids (Instrument 2).


Technically the Project comprises two parts:

– electrochemical part, which involves research and development of a electrochemical sensors, analytical methods and algorithms used to evaluate the microelemental and immune status of the organism;


– design part, which includes development of algorithms and programs in control of the experimental procedure and processing of results, and creation of prototypes of portable instruments operating with the aforementioned sensors.

The following items will be developed during the Project works:

– a solid-phase electrochemical sensor with a mediator function for evaluation of the redox potential of biological liquids in the human organism;


– a solid-phase electrochemical sensor for determination of the TDS status of the human organism;
– solid-phase electrochemical sensors for determination of microconcentrations of Cu, Pb, Cd, Zn, Ni, and Se in biological liquids (blood, urine) used to evaluate the microelemental status of the human organism;
– analytical methods;
– programs in control of the sensors, reading and processing of information:
– a portable computerized instrument for determination of the redox (including thioldisulfide) balance used to assess the immune status of the human organism. It will be possible to use this instrument at stationary laboratories of large hospitals and in the field;
– a portable computerized instrument for determination of the microelemental composition of biological liquids.

The methods of stripping voltammetry, chronoamperometry, cyclic voltammetry, and chronopotentiometry will be used as research methods of the Project. The methods of atomic absorption spectrometry (AAS) and inductively coupled plasma mass spectrometry (ICP MS) will be used in independent parallel experiments to verify validity of the obtained results.

Various methods of formation and processing of the electrochemical signal (response) will be studied in order to determine the optimal polarization regime of the electrodes providing the most reliable information. The conditions of formation and regeneration of the sensor surface will be found.

The obtained data will be used to develop methods and algorithms, analysis programs, and prototypes of the portable instruments.

The Project has social and commercial significance, since the instruments to be developed under the Project are very important for health protection.

The available material basis and the experience gained during fulfillment of ISTC Projects Nos. 342-96 and 342B will permit cutting the Project expenditures. The financial support to the Project will help preserve the creative body of workers, which includes specialists in nuclear weapons, and direct their efforts to solution of problems concerned with health protection, medicine, and peaceful production.


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