Приоритет — индустрия наносистем

Проект направлен на разработку аналитической платформы для оценки токсичности наноматериалов и ее снижения с помощью природных полимеров, создание проекта методических рекомендаций для экспериментальной проверки безопасности наноматериалов и соответствует направлениям исследований, поддерживаемых в рамках Технологических платформ «Биоиндустрия и биоресурсы — БиоТех2030» и «Технологии экологического развития».

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Комплексный инвестиционный проект

«Разработка аналитической платформы для биотестирования и снижения токсичности наноматериалов с использованием природных полимеров»

Код по Общероссийскому классификатору видов экономической деятельности, продукции и услуг (ОКДП) ОК 004-93 – 7310000

Основания для выполнения проекта

Создание современной научно-технологической аналитической платформы для оценки токсичности наноматериалов и ее снижения с помощью природных полимеров позволит создать методические рекомендации для экспериментальной проверки безопасности наноматериалов.

Проект реализуется в соответствии с государственными документами, определяющими основные направления развития наноиндустрии, соответствует современному направлению критических технологий, связанному с созданием новых высокочувствительных и высокоспецифичных систем оценки токсичности наноматериалов.

Разрабатываемые в рамках проекта технологии относятся к приоритетным направлениям развития науки, технологий и техники в Российской Федерации, в частях: «Индустрия наносистем», а также критическим технологиям Российской Федерации, перечень которых утвержден Указом Президента Российской Федерации от 7 июля 2011 г. № 899, в частях: «Нано-, био-, информационные, когнитивные технологии», «Технологии диагностики наноматериалов и наноустройств», «Технологии мониторинга и прогнозирования состояния окружающей среды, предотвращения и ликвидации ее загрязнения».

Проект направлен на создание аналитической платформы для оценки токсичности наноматериалов, что способствует эффективной реализации целей и задач, поставленных в Плане мероприятий («дорожная карта») «Перечень технологических направлений (комплексных технологий) дорожной карты развития нанотехнологий в Российской Федерации»

Перечень технологических направлений (комплексных технологий) дорожной карты развития нанотехнологий в Российской Федерации

Краткая характеристика продукции

Возможности нанотехнологий позволяют все полнее характеризовать новые продукты, однако все еще мало известно об их взаимодействии с живыми организмами. В то же время эти вопросы являются наиболее важными при разработке безопасных наносистем. На сегодняшний день насчитывается более 2300 видов продукции на основе наночастиц. Их широкое применение требует разработки подходов и систем оценки безопасности.

Наноматериалы по химическим и физическим свойствам радикально отличаются от свойств веществ в форме сплошных фаз или макроскопических дисперсий, в связи с чем исследованию их биологической активности уделяется особое внимание. В специальных постановлениях, в том числе, документах, утвержденных Главным санитарным врачом РФ — «Методические рекомендации по выявлению наноматериалов, представляющих потенциальную опасность для здоровья человека» [МР 1.2.2522-09], «Токсиколого-гигиеническая оценка безопасности наноматериалов.

Методические указания» [МУ 1.2.2520-09; МУ 1.2. 2634-10; МУ 1.2. 2635-10; Концепция токсикологических исследований…, 2007; ISO /TR 12885:2008(E), стандарты BSI PD 6699-1:2007; REPORT R-589 IRSST и др.) указывается на необходимость исследований экотоксикологической и биологической активности новых материалов, а также представлены рекомендации, касающиеся оценки вреда здоровью, безопасности при профессиональном воздействии наноматериалов.

Несмотря на большие усилия, предпринимаемые в этой сфере, пока еще нет какого-либо детализированного описания и классификации ответных реакций живых организмов на сконструированные материалы (Андреев и др., 2008; Brayner, 2007; Nohynek et al., 2008; Handy et al, 2008; Nasir, 2010; Hu and Gao, 2010; и др.). Биотический контроль, осуществляемый как после применения наноструктурированных материалов, так и на разных этапах их создания, должен обеспечить надежность оценки риска и последствий химических загрязнений природных сред.

Актуальной проблемой является также поиск и создание экологически безопасных детоксицирующих агентов, обладающих высоким сорбционным потенциалом по отношению к токсичным веществам и наночастицам. Для разработки сорбентов такого типа весьма перспективным представляется использование природных высокомолекулярных соединений — гуминовых веществ (ГВ) благодаря их уникальным биологическим свойствам, таким как биосовместимость, устойчивость и полифункциональность.

Особую важность использование «зеленых» химикатов, гуминовых веществ представляет в контексте концепции Технологических платформ «Технологии экологического развития» (http://tp-eco.ru/assets/files/Strategicheskaia_programma.pdf) и «Биоиндустрия и биоресурсы — БиоТех2030» (Меморандум об образовании ТП от 28 апреля 2011 г., http://www.биотех2030.рф).

Наличие в молекулах ГК широкого спектра функциональных групп, таких как карбоксильные, гидроксильные, карбонильные, азот и серусодержащие, хинонные и семихинонные в сочетании с присутствием ароматических фрагментов обуславливает их высокую реакционную способность по отношению к металлсодержащим токсикантам, включая и наночастицы, связывая их в прочные комплексы.

Экологические последствия такого связывания – изменение форм существования металлов и их миграционной способности, уменьшение биодоступности и токсичности. Связанное вещество свою токсичность теряет.

В предлагаемом проекте будет предложена оригинальная аналитическая система оценки экотоксичности наноматериалов, основанная на многовидовых биотест-системах с учетом свойств среды биотестирования (наличия полимерных компонентов); будут выявлены наиболее чувствительные тест-функции к металл- и углеродсодержащим наноматериалам в стандартных биотест-системах, которые можно рекомендовать для практического использовании; будет создан проект методических рекомендаций для комплексного биотестирования токсичности наноматериалов; выявлена степень снижения токсичности суспензий наноматериалов и других экотоксикантов в присутствии ранее разработанных и новых сорбентов; будут получены стабилизированные гуминовыми кислотами нанокомпозиционные материалы, обладающие свойствами как избирательных сорбентов, так и специфическими свойствами магнитных материалов.

Для достижения цели проекта будет проведено комплексное исследование сорбционных свойств гуминовых кислот в процессе формирования полимерных композитов на основе матрично-стабилизированных природными полимерами магнитоактивных наночастиц по отношению к ионам свинца и наночастицам.

Будут выявлены закономерности, связывающие фундаментальные характеристики получаемых нанокомпозитов (микроструктуру, дисперсность наночастиц и характер их распределения по размеру и в пространстве матрицы, морфологию) с их сорбционными свойствами (сорбционной емкостью, селективностью, стабильностью и др.). Еще один круг фундаментальных задач будет связан с изучением молекулярного механизма адсорбционных процессов в системе полимерный сорбент – ионы металла.

Общая стоимость инвестиционного проекта: 84 млн. руб.
Размер запрашиваемой субсидии для выполнения НИОКР: 50% от стоимости инвестиционного проекта (42 млн. руб.).

Требования к НИОКР

Цель работы:

Разработка аналитической платформы для оценки токсичности наноматериалов и ее снижения с помощью природных полимеров, создание проекта методических рекомендаций для экспериментальной проверки безопасности наноматериалов.

Задачи работы

В процессе выполнения НИОКР должны быть решены следующие важнейшие задачи:

  1. Проведен аналитический обзор по проблеме оценки токсичности наноматериалов.
  2. Проведены патентные исследования по методам оценки токсичности наноматериалов и ее снижения с помощью природных полимеров.
  3. Получены природные полимеры (гуминовые и пектовые кислоты) и их производные для снижения токсичности наночастиц.
  4. Синтезированы структурно-упорядоченные наночастицы оксидов железа (магнетита) с использованием различных методов.
  5. Исследована морфология, пористая структура и фазовый состав полученных материалов методами ИК- и месс-бауеровской спектроскопии, сканирующей электронной микроскопии, рентгенофазового анализа и других методов.
  6. Проведена комплексная оценка токсичности суспензий наночастиц различной природы в предлагаемой аналитической системе, основанной на тест-функциях стандартизованных тест-культур.
  7. Проведена оценка влияния сорбентов на токсичность наночастиц и ионов тяжелых металлов.
  8. Проведена технико-экономическая оценка рыночного потенциала полученных результатов.
  9. Разработаны методические рекомендации для экспериментальной проверки безопасности наноматериалов.

Получаемые в конце работы результаты (технологии, подготовленные к промышленному использованию):

В результате НИОКР должны быть разработаны и оптимизированы новые методы оценки токсичности наноматериалов и ее снижения с помощью природных полимеров, разработаны методические рекомендации.

Характеристики технологического процесса производства тест-систем соответствуют следующим показателям:

При определении экотоксикологической безопасности наноматериалов будет использован набор биотестов, что отражает экосистемный подход и позволяет дать наиболее корректную оценку токсичности анализируемых объектов. Наноматериалы будут исследованы в лабораторных экспериментах по реакции тест-организмов широкого спектра видов: бактерии – Escherichia coli — высшие растения Sinapis alba, зеленые протококковые водоросли Scenedesmus quadricauda, простейшие — инфузории Paramecium caudatum, культуры половых клеток теплокровных животных (быка) in vitro.

Исследования экотоксичности и биоактивности образцов будут проводиться на базе сертифицированной лаборатории биотестирования, www.letap.ru, аттестат аккредитации РОСС RU 0001.513050. Экспериментальная проверка будет проводиться по следующим методикам выполнения измерений (МВИ. Токсикологические методы контроля), рекомендованным для целей государственного экологического контроля и зарегистрированным в Федеральном реестре (ФР МВИ, Токсикологические методы контроля) и реестре природоохранных нормативных документов федерального уровня (ПНДФ):

  1. Методика определения токсичности с использованием равноресничных инфузорий Paramecium caudatum Ehrenberg (ФР.1.39.2006.02506);
  2. Методика определения токсичности по изменению уровня флуоресценции хлорофилла и численности клеток водорослей (ФР.1.39.2007.03223).
  3. Методика выполнения измерений индекса по изменению подвижности половых клеток млекопитающих in vitro (ФР.1.31.2009.06301)
  4. Методика выполнения измерений токсичности с использованием бактериальной тест-системы «Эколюм» ПНД Ф Т 16.1:2.3:3.8-04.
  5. Методика измерений биологической активности гуминовых веществ методом фитотестирования (ФР.1.31.2012.11560 ).

Введение магнитоактивных наночастиц в объем полимерной матрицы будет осуществляться методом in situ в водном растворе высокомолекулярного соединения (или его суспензии). Получение нанокомпозитов методом химического осаждения in situ заключается в формировании гидратированного оксида железа (магнетита) из разновалентных солей железа, взятых в количественных соотношениях Fe (2+)/Fe(3+) = 1:2, в щелочной среде и в присутствии стабилизирующего полимерного лиганда. Благодаря адсорбции макромолекул на межфазных границах и образованию прочных химических связей повышается агрегативная устойчивость формирующихся наночастиц и происходит их стабилизация. Исследования сорбционных свойств полученных полимерных сорбентов по отношению к наночастицам и ионам свинца будут проведены в статических и динамических условиях. Для описания процессов сорбции будет использованы изотермы Фрейндлиха и Лэнгмюра, позволяющая определить величину максимальной сорбции и константы равновесия.

Основные этапы работ

Предлагаемая разработка должна быть выполнена в 3 этапа.

Этап 1. Теоретическое исследование путей создания аналитической платформы на основе комплексной системы оценки токсичности наноматериалов

1.1 Аналитический обзор современной научно-технической, нормативной, методической литературы, затрагивающей научно-техническую проблему, исследуемую в рамках НИР, в том числе обзор научных информационных источников: статьи в ведущих зарубежных и российских научных журналах, монографии и патенты — не менее 25-ти научно-информационных источников за 2007 – 2014 г.г.

1.2 Обоснование выбора методов и средств, направления исследований и способы решения поставленных задач;

1.3 Сравнительная оценка вариантов возможных решений исследуемой проблемы с учетом результатов прогнозных исследований, проводившихся по аналогичной тематике;

1.4 Патентные исследования по выбранной тематике согласно ГОСТ Р 15.011-96.

1.5 Исследование современных подходов и выбор наиболее эффективных способов и приборов для оценки токсичности наноматериалов.

1.6 Получение и физико-химическая характеристика природных полимеров.

Этап 2. Разработка проектов методики диагностики токсичности наноматериалов, включающий пробоподготовку и условий измерения в тест-системах, анализ полученных результатов.

2.1 Адаптация состава компонентов биотест-системы для оценки токсичности наноматериалов;

2.2 Разработка программы исследовательских испытаний на основе предлагаемой аналитической системы для оценки токсичности наноматериалов и наночастиц с использованием полимерных сорбентов;

2.3 Выработка предложений и рекомендаций по использованию предлагаемой аналитической системы.

2.4 Проведение исследовательских испытаний аналитической системы для оценки токсичности наноматериалов и наночастиц на примере модельных образцов по разработанной Программе.

2.5 Обработка результатов с помощью современного программного обеспечения для обеспечения точности измерений – не менее 10%.

2.6 Получение и физико-химическая характеристика наночастиц оксидов железа.

2.7 Оценка токсичности наночастиц с использованием батареи биотестов.

Этап 3. Разработка рекомендаций и предложений по использованию результатов НИР в реальном секторе экономики, а также в дальнейших исследованиях и разработках.

3.1 оценка влияния сорбентов на токсичность наночастиц и ионов тяжелых металлов.

3.2. Выполнение технико-экономической оценки рыночного потенциала полученных результатов.

3.3 Разработка проекта технического задания на проведение прикладных НИР по теме: «Формирование селективных полимерных сорбентов для иммобилизации наночастиц и экотоксикантов».

3.4 Разработка проекта методических рекомендаций для диагностики токсичности наноматериалов, включающий пробоподготовку и условия измерения в тест-системах, анализ полученных результатов.

Результаты реализации комплексного инвестиционного проекта

Технические и экономические характеристики разрабатываемой научно-технической продукции.

В результате выполнения проекта должны быть:

  1. Подготовлен отчет о НИР, содержащий:

а) обзор и анализ современной научно-технической, нормативной, методической литературы, затрагивающей научно-техническую проблему, исследуемую в рамках НИР, а именно анализ литературных данных по современным методам диагностики токсичности наноматериалов;

б) обоснование выбора направления исследований, методов и средств решения задач, поставленных в рамках НИР;

в) теоретическое исследование путей создания аналитической платформы на основе комплексной системы оценки токсичности наноматериалов;

г) результаты экспериментальных исследований влияния различных наноматериалов на разрабатываемые тест системы и другие результаты НИР;

д) сравнительный анализ характеристик предлагаемого подхода и существующих прототипов и аналогов.

е) технико-экономическую оценку результатов НИР;

ж) обобщение и выводы по результатам НИР;

и) рекомендации и предложения по использованию результатов НИР в реальном секторе экономики, а также в дальнейших исследованиях и разработках;

  1. Разработан макет аналитической системы оценки токсичности наноматериалов.
  2. Разработаны программа и методики исследовательских испытаний разработанной аналитической системы оценки токсичности в присутствии полимеров
  3. Разработаны методики синтеза и анализа наноматериалов и полимерных сорбентов наноматериалов.
  4. Разработан Проект технического задания на проведение прикладных НИР по теме «Формирование селективных полимерных сорбентов для иммобилизации наночастиц и экотоксикантов».
  5. Разработан Проект методических рекомендаций для диагностики токсичности наноматериалов.

Разработанный отчет о НИР, научно-технические основы создания комплексной оценки токсичности наноматериалов и технологии использования полимерных сорбентов для их иммобилизации должны обеспечить получение новых данных в области развития экологически безопасных биотехнологий.

Полученные результаты и разработанные подходы должны быть ориентированы на применение в прикладных исследованиях по использованию спектра биотестов для оценки токсичности и сорбентов для ее снижения у наноматериалов металлической и углеродной природы.

Продукты должны быть разработаны с использованием современных подходов экотоксикологии и «зеленой химии», требующих оптимизации технологических процессов по принципу минимальной отходности и максимальной безопасности как интермедиатов, так и целевых продуктов. Основными критериями предполагаемых разработок должна быть возможность использования их для экспрессной оценки при производстве экологически безопасной продукции и обеспечения ее экономической значимости.

Разрабатываемые технологические решения по созданию технологии комплексной оценки токсичности наноматериалов и использованию полимерных сорбентов для снижения их токсичности должны быть конкурентоспособны по сравнению с существующими подходами.

Должна быть проведена технико-экономическая оценка рыночного потенциала полученных результатов.

Конечными рыночными продуктами являются аналитическая система оценки токсичности наноматериалов и разработанный проект методических рекомендаций для практического ее использования при оценке наноматериалов в чистом виде и в присутствии полимерных природных молекул. Предлагаемая аналитическая система будет опираться на оперативное определение токсичности в краткосрочных острых экспериментальных проверках на стандартизованных тест-культурах разной видовой принадлежности. Вместе с тем будут предложены оригинальные системы учета фитоэффекта на основе полученного патента.

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