Final Report Summary - LOCNANOMOT (New lab-on-a-chip microsystems based on active transport by synthetic micro/nanomotors)
The LOCNANOMOT project aims to develop new miniaturized lab-on-a-chip (LOC) systems for multiplexed detections using functionalized artificial micro/nanomotors modified with different receptors. To achieve the stated goal, a primary challenge of the outgoing phase was the development of new receptor-functionalized catalytic micro/nanomotors capable of performing multiple nanoscale operation. The second objective focused on the integration of the newly developed micro/nanomotors into LOC devices. The third objective, at the return phase, focused on the applicability of these new devices for the isolation and detection of contaminants in foodstuffs and clinical relevance analytes in complex biological samples. To ensure successful achievement of the project objectives and goals, five main phases were planned. These five aims correspond to twelve different tasks to be accomplished in 36 months. In parallel to the research activities performed since the beginning of the project, dissemination of the result was carried out to promote knowledge sharing.
1. Fabrication and functionalization of artificial micro/nanomotors for on-chip applications.
2. Development of new lab-on-a-chip devices based on active transport by using artificial micro-/nanomotors.
3. Application of the newly developed lab-on-a-chip devices for the determination of biological molecules in complex samples.
4. Design of new LOC systems based on active transport for the determination of several contaminants in foodstuffs.
5. Dissemination on the results.
In order to fulfil the first objective, we evaluated several strategies to develop new nanomotors with improved speed, towing force and versatility for on-chip applications. In particular, we studied the effect of different monomers composition, electropolymerized outer layers and catalytic layers upon the morphology and locomotion of tubular microengines or Janus microparticles. We also evaluated the functionalization of such micromotors with magnetic layers or Au segments for further surface modification (via thiol chemistry) with different receptors for the isolation of biological threats. During this first objective, several main results were achieved: 1) A fundamental study about the enhanced transport and fluid mixing imparted by the movement of tubular micromotors, catalytic nanowires and Janus particles was published in the leading peer review journal Langmuir. This study will have important implications for the manipulation of fluids and mixing of reagents in situations where mechanical stirring is not possible (LOC formats); 2) The preparation of different Janus micromotors by sputter deposition of a catalytic layer (Pt or Ag) onto silica, polystyrene and high-active surface particles (activated carbon, zeolite and magnesium) open new avenues for novel applications, including on-chip enrichment, bacteria isolation and environmental remediation. The results derived from this work were published in leading journals (Small, ACS Nano and Advanced Functional Materials) and presented in international congress; 3) A new sensing silver protocol based on the motion of metallic nanowires, including both numerical and experimental simulations, was reported and published in the journal Nanoscale.
In a second objective, new LOC devices based on active transport by using artificial micro-/nanomotors were developed. On a first step, several strategies for the precise motion control and cargo isolation/manipulation of such microengines within complex channels were evaluated. Another goal(s) achieved were the optimization of the composition and concentration of the fuel(s) in the power output of micro/nanomotors, the enhancement of the catalytic decomposition of the classic hydrogen peroxide fuel by the modification of the microengines with graphene and the identification of new in situ fuels (water-driven magnesium micromotors). In the next steps we applied such LOC for multiplexed detections of biological and heavy metal targets. To this end, we optimized the design of catalytic microengines (graphene-based micromotors, biomimetic microengines and QDs microsensors) and its subsequent integration on PDMS chips. During this second objective, the following main results were achieved: 1) Tubular microengines composed entirely by one of the cutting edge nanomaterials, graphene, were synthesized for the first time. The unique surface properties of graphene allowed for the incorporation of different receptors, contributing thus to the development of the next generation of LOC systems. These results were published in the journal Small; 2) We reported on the preparation is the first biomimetic motors, prepared by the incorporation of red-blood cell particles on the surface of ultrasound-propelled Au nanowires. Such motor sponges connect artificial nanomotors with biological entities and hold great promise for bacteria isolation and detoxification applications. A paper was published in Advanced Functional Materials; 3) We have also reported, for the first time, the incorporation of quantum-dot (QDs) nanocrystals in the surface of template-prepared microengines. The preparation protocol is highly versatile, allowing for the incorporation of QDs with different emission wavelengths for the simultaneous detection of multiple analytes. The potential of such tiny "microsensor" has been proved for on-chip multiplexed detection of mercury and bacteria in biological samples. The dynamic movement of the microsensors through the microchip reservoirs avoid the use of pumps to move fluids, allowing further miniaturization and reducing the volume of sample required for the analysis. Such results were published in Chemical Communications and ACS Applied Materials and Interfaces. Also, the attached figure depicts a diagram of such nanomotor-based LOC.
The third objective, at the return phase, was devoted to test the applicability of these newly developed LOC systems based on active nanomotors-transport for the isolation and detection of contaminants and rare cells in complex biological and food samples. We studied first the potential of water driven Mg-Janus micromotors for the degradation and detection of non-electroactive phthalates (persistent organic compounds) in screen-printed electrodes. On a second step different carbon nanomaterials were explored, for the first time, as advanced surface materials for the preparation of highly efficient tubular microengines. Next we tested its performance in complex media for enhanced cargo pick-up and delivery. Finally, we integrate such highly efficient micromotors into the different reservoirs of PDMS chips for rare cell and bacteria analysis in food and biological samples. The main results derived from this third and final objective can be summarized as follows: 1) We developed a novel Janus micromotor-based strategy for the direct determination of non-electroactive analytes in food and biological samples. The study holds great potential for on-chip monitoring of such toxic compounds in complex food (milk, whiskey) and biological samples towards novel point-of-care devices. The results derived from this study were published in Analytical Chemistry; 2) Several tubular micromotors based on carbon nanomaterials were synthetized for the first time. Such new protocol opens new avenues for the universal preparation of a wide ‘nano-library’ of carbon based multifunctional microengines for a myriad of LOC applications, i.e. cargo transportation, bacteria isolation and determination, etc; 3) A LOC system integrating carbon-nanomaterial based micromotors was applied for rare cell and bacteria isolation and analysis in food and biological samples, achieving thus the final goal of the LOCNANOMOT project. 4) We also write and published two timely reviews in leading-peer review journals (Lab on a chip and Trends in Analytical Chemistry), for further dissemination of the results derived from the project.
The current state-of-the-art of nanotechnology lies on the development of a wide range of synthetic nano/microscale machines for practical biomedical, analytical and on-chip applications. So far, only few reports deal with the use of these motors as onboard devices for LOC platforms. The final result of the LOCNANOMOT project provided a major step toward the design of integrated microsystems that perform a series of simultaneous tasks, leading to new LOC formats for a wide range of biomedical, analytical and technological applications (i.e. rapid pathogen detection, clinical diagnosis, forensic science, electrophoresis, flow cytometry, blood chemistry analysis, protein and DNA analysis). The methodological approach pioneered in the proposed project will be of great value for the European Community since it will contribute to its growth, competitiveness and sustainable development objectives. Furthermore, the convenient marriage of nanomotors and lab-on-a-chip platforms will be important for the establishment of personalized medicine and for environmental and food safety assurance.
1. Fabrication and functionalization of artificial micro/nanomotors for on-chip applications.
2. Development of new lab-on-a-chip devices based on active transport by using artificial micro-/nanomotors.
3. Application of the newly developed lab-on-a-chip devices for the determination of biological molecules in complex samples.
4. Design of new LOC systems based on active transport for the determination of several contaminants in foodstuffs.
5. Dissemination on the results.
In order to fulfil the first objective, we evaluated several strategies to develop new nanomotors with improved speed, towing force and versatility for on-chip applications. In particular, we studied the effect of different monomers composition, electropolymerized outer layers and catalytic layers upon the morphology and locomotion of tubular microengines or Janus microparticles. We also evaluated the functionalization of such micromotors with magnetic layers or Au segments for further surface modification (via thiol chemistry) with different receptors for the isolation of biological threats. During this first objective, several main results were achieved: 1) A fundamental study about the enhanced transport and fluid mixing imparted by the movement of tubular micromotors, catalytic nanowires and Janus particles was published in the leading peer review journal Langmuir. This study will have important implications for the manipulation of fluids and mixing of reagents in situations where mechanical stirring is not possible (LOC formats); 2) The preparation of different Janus micromotors by sputter deposition of a catalytic layer (Pt or Ag) onto silica, polystyrene and high-active surface particles (activated carbon, zeolite and magnesium) open new avenues for novel applications, including on-chip enrichment, bacteria isolation and environmental remediation. The results derived from this work were published in leading journals (Small, ACS Nano and Advanced Functional Materials) and presented in international congress; 3) A new sensing silver protocol based on the motion of metallic nanowires, including both numerical and experimental simulations, was reported and published in the journal Nanoscale.
In a second objective, new LOC devices based on active transport by using artificial micro-/nanomotors were developed. On a first step, several strategies for the precise motion control and cargo isolation/manipulation of such microengines within complex channels were evaluated. Another goal(s) achieved were the optimization of the composition and concentration of the fuel(s) in the power output of micro/nanomotors, the enhancement of the catalytic decomposition of the classic hydrogen peroxide fuel by the modification of the microengines with graphene and the identification of new in situ fuels (water-driven magnesium micromotors). In the next steps we applied such LOC for multiplexed detections of biological and heavy metal targets. To this end, we optimized the design of catalytic microengines (graphene-based micromotors, biomimetic microengines and QDs microsensors) and its subsequent integration on PDMS chips. During this second objective, the following main results were achieved: 1) Tubular microengines composed entirely by one of the cutting edge nanomaterials, graphene, were synthesized for the first time. The unique surface properties of graphene allowed for the incorporation of different receptors, contributing thus to the development of the next generation of LOC systems. These results were published in the journal Small; 2) We reported on the preparation is the first biomimetic motors, prepared by the incorporation of red-blood cell particles on the surface of ultrasound-propelled Au nanowires. Such motor sponges connect artificial nanomotors with biological entities and hold great promise for bacteria isolation and detoxification applications. A paper was published in Advanced Functional Materials; 3) We have also reported, for the first time, the incorporation of quantum-dot (QDs) nanocrystals in the surface of template-prepared microengines. The preparation protocol is highly versatile, allowing for the incorporation of QDs with different emission wavelengths for the simultaneous detection of multiple analytes. The potential of such tiny "microsensor" has been proved for on-chip multiplexed detection of mercury and bacteria in biological samples. The dynamic movement of the microsensors through the microchip reservoirs avoid the use of pumps to move fluids, allowing further miniaturization and reducing the volume of sample required for the analysis. Such results were published in Chemical Communications and ACS Applied Materials and Interfaces. Also, the attached figure depicts a diagram of such nanomotor-based LOC.
The third objective, at the return phase, was devoted to test the applicability of these newly developed LOC systems based on active nanomotors-transport for the isolation and detection of contaminants and rare cells in complex biological and food samples. We studied first the potential of water driven Mg-Janus micromotors for the degradation and detection of non-electroactive phthalates (persistent organic compounds) in screen-printed electrodes. On a second step different carbon nanomaterials were explored, for the first time, as advanced surface materials for the preparation of highly efficient tubular microengines. Next we tested its performance in complex media for enhanced cargo pick-up and delivery. Finally, we integrate such highly efficient micromotors into the different reservoirs of PDMS chips for rare cell and bacteria analysis in food and biological samples. The main results derived from this third and final objective can be summarized as follows: 1) We developed a novel Janus micromotor-based strategy for the direct determination of non-electroactive analytes in food and biological samples. The study holds great potential for on-chip monitoring of such toxic compounds in complex food (milk, whiskey) and biological samples towards novel point-of-care devices. The results derived from this study were published in Analytical Chemistry; 2) Several tubular micromotors based on carbon nanomaterials were synthetized for the first time. Such new protocol opens new avenues for the universal preparation of a wide ‘nano-library’ of carbon based multifunctional microengines for a myriad of LOC applications, i.e. cargo transportation, bacteria isolation and determination, etc; 3) A LOC system integrating carbon-nanomaterial based micromotors was applied for rare cell and bacteria isolation and analysis in food and biological samples, achieving thus the final goal of the LOCNANOMOT project. 4) We also write and published two timely reviews in leading-peer review journals (Lab on a chip and Trends in Analytical Chemistry), for further dissemination of the results derived from the project.
The current state-of-the-art of nanotechnology lies on the development of a wide range of synthetic nano/microscale machines for practical biomedical, analytical and on-chip applications. So far, only few reports deal with the use of these motors as onboard devices for LOC platforms. The final result of the LOCNANOMOT project provided a major step toward the design of integrated microsystems that perform a series of simultaneous tasks, leading to new LOC formats for a wide range of biomedical, analytical and technological applications (i.e. rapid pathogen detection, clinical diagnosis, forensic science, electrophoresis, flow cytometry, blood chemistry analysis, protein and DNA analysis). The methodological approach pioneered in the proposed project will be of great value for the European Community since it will contribute to its growth, competitiveness and sustainable development objectives. Furthermore, the convenient marriage of nanomotors and lab-on-a-chip platforms will be important for the establishment of personalized medicine and for environmental and food safety assurance.