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Three-dimensionally printed electrochemical systems for biomedical analytical applications
Available online at www.sciencedirect.com
ScienceDirect
Current Opinion in
Electrochemistry
Review Article
Three-dimensionally printed electrochemical systems for biomedical analytical applications Martin Pumeraa,b Abstract
Additive manufacturing (3D-printing) has revolutionized many areas of the manufacturing. Three-dimensional printing offers enormous potential to biomedical devices, including electroanalytical systems. The motivation for 3D printing is rapid prototyping and decentralized customizable fabrication of bioanalytical systems in the diverse and remote areas of the globe. We overview the recent trends and discuss the fabrication and applications of 3D printed polymer/carbon and metal electrodes and whole electrochemical systems for biomedical applications and DNA detection. We show that sky is the limit and envision whole analytical systems, including electronics, to be 3D printed in the future for diagnostics in the remote areas of the globe. Addresses a Center for the Advanced Functional Nanorobots, Department of Inorganic Chemistry, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague 6, Czech Republic b Future Energy and Innovation Laboratory, Central European Institute ova 656/123, of Technology, Brno University of Technology, Purkyn Brno, CZ-616 00, Czech Republic Corresponding author: Pumera, Martin (pumera.research@gmail. com)
Current Opinion in Electrochemistry 2019, 14:133–137
medicine and biomedical applications [6]. Threedimensionally printed structures created for on-demand use by medical doctors during surgeries caught attention of the professionals and public as well [7e9]. One of the very important subsections of 3D printing is biosensing devices. In this review, we wish to discuss detection of biomarkers, biologically active compounds, and DNA on the 3D printed electrochemical sensors and systems. 3D-printing of bioanalytical systems allows for tailored and decentralized fabrication of the devices. 3D-printing of electroanalytical systems needs to overcome many challenges. The material must be electrically conducting in the final form. It must have electroactive surface (this is a challenge in the case of polymer/graphene 3D printed structures), and the surface needs to have suitable electrochemical window (this may be an issue in the case of metal electrodes). In addition, the surface needs to be easy to functionalize with biorecognition elements, that is, DNA or protein. We will review all these challenges and present opportunities this technology and materials offer. We divide the review into two parts, discussion of distinctive properties of 3D printed metal and polymer electrodes, in the context of biomedical sensing applications.
This review comes from a themed issue on Bioelectrochemistry Edited by Elena Ferapontova and Miroslav Fotja
3D printed metal electrodes
For a complete overview see the Issue and the Editorial
3D-printing of metals requires significantly more expensive equipment than polymer filament printing. The metal is typically iron, steel, titanium, or aluminum. The iron-based 3D printed electrodes are the most economical, and they do not passivate; however, to create usable electrochemical reproducible surfaces, they need to be coated with another metal. This is typically done with gold via electrodeposition method (Fig. 1) [10].
Available online 11 February 2019 https://doi.org/10.1016/j.coelec.2019.02.001 2451-9103/© 2019 Published by Elsevier B.V.
Keywords Additive manufacturing, 3D printing, Biosensor, Electrochemistry, DNA, Medicine.
Introduction 3D-printing, or additive manufacturing, revolutionized many fields of materials science and engineering, ranging from nanofabrication of electronics [1], sensors [2], and energy devices [3] to 3D printing of the buildings on the Earth or on the Moon [4,5]. One of the very important areas of the 3D printing where the decentralized fabrication of on-demand and tailorable 3D structures find a great scope of applications is www.sciencedirect.com
The 3D printed helical electrode was coated with gold and functionalized with ssDNA probe with a terminal -SH group [11]. Target and noncomplementary ssDNA was introduced to investigate whether the 3D printed electrode can be used as biosensor, and methylene blue intercalator was used as a label (Fig. 2). In series of articles, we demonstrated that 3D printed metal electrodes are of high importance for the Current Opinion in Electrochemistry 2019, 14:133–137
134 Bioelectrochemistry
Figure 1
Current Opinion in Electrochemistry
Typical procedure of fabrication of 3D printed electrodes. From left to right: computer-assisted design, 3D printed electrode, and 3D printed electrode covered with appropriate metal for particular application. 3D, three-dimensionally. Reprinted with permission from Ambrosi and Pumera [10].
detection of drugs such as acetaminophen [12] and biomarkers such as dopamine [12], ascorbic acid, and uric acid [13]. All these required gold-coated iron electrodes.
Figure 2
3D printed carbon electrodes 3D-printing of polymer and graphene/polymer requires comparably cheap systems under the cost of 1000 EUR, but it poses another challenge. The 3D printed structures are conductive, but the surface of the structure is covered with a very thin layer of polymer and initially the electrochemical performance is poor. One needs to ‘activate’ the surface. This can be done by several ways. Dimethylformamide (DMF) can be used to dissolve the top protective layer of polymer and to expose graphene flakes in polymer/graphene 3D printed electrodes. Fig. 3 shows the difference of nonactivated and activated polylactic acid/graphene 3D printed electrode for the detection of ascorbic acid and other electrochemical probes [14]. Another way to activate the polymer/graphene electrode is to use electrochemical activation d via anodization (oxidation) potential [15]. This leads to highly active surfaces; however, it is preferable to combine this method with DMF chemical treatment for enhanced performance [16].
Conclusions & outlook 3D-printing allows to 3D print whole electrochemical systems, including the electrode, beaker, and lid or the whole flow system (Fig. 4) [17e19]. Such on-demand capability allows rapid prototyping and on-spot device Current Opinion in Electrochemistry 2019, 14:133–137
Current Opinion in Electrochemistry
Metal 3D printed electrodes for electrochemical DNA sensing. (a) Schematic representation of the biosensing protocol used. A DNA recognition element, -SH probe, was first covalently immobilized onto the gold-plated 3D printed helix electrode. Subsequently, a blocking step with MCH (not shown) was performed to cover up the remaining electrode surface. The modified electrode was then incubated with a DNA target for hybridization reaction. Finally, the electrode was exposed to methylene blue solution, and the methylene blue molecules intercalated into the double helix structure of the hybridized double-stranded DNA. (b) Histograms representing the methylene blue reduction peak current values obtained after hybridization with complementary or noncomplementary DNA targets. The amount of DNA targets used was 100 pmol. Error bars correspond to replicate experiments. The inset demonstrates the respective differential pulse voltammograms acquired. All measurements were performed in 20 mM Tris–HCl (pH 7.0) under ambient conditions. 3D, threedimensionally. Reprinted with permission from Loo et al. [11].
www.sciencedirect.com
www.sciencedirect.com Figure 3
Activation of polymer/graphene 3D printed electrodes via DMF. Cyclic voltammograms of 3D printed electrodes, ring and disc shaped (I and II, respectively), recorded for various redox probes (1 mM) at a scan rate of 100 mV s−1. (a) Ru(NH3)6Cl3. (b) Fc-COOH. (c) K3Fe(CN)6:K4Fe(CN)6. (d) FeCl3. (e) Ascorbic acid. See experimental conditions for more details. Dashed lines: nonactivated electrodes. Full lines: activated electrodes. 3D, three-dimensionally. Reprinted with permission from Manzanares Palenzuela et al. [14].
3D printing for biomedical applications Pumera 135
Current Opinion in Electrochemistry 2019, 14:133–137
Current Opinion in Electrochemistry
136 Bioelectrochemistry
Figure 4
Current Opinion in Electrochemistry
Power of 3D printing for electrochemical systems. All items shown, including metal electrodes, containers, etc. are 3D printed. 3D, three-dimensional. Reprinted with permission from Ambrosi and Pumera [10].
fabrication and utilization, which is important for decentralized medicine. 3D-printing of whole biomedical analytical systems (i.e. in flow analysis setup) [20] is the next step on the route to customized decentralized on-demand biomedical sensing and analysis [21].
6.
Hsieh C-T, Liao C-Y, Dai N-T, Tseng C-S, Yen BL, Hsu S-H: Appl Mater Today 2018, 12:330.
7.
Chae MP, Rozen WM, McMenamin PG, Findlay MW, Spychal RT, Hunter-Smith DJ: Front Surg 2015, 2:25, https://doi.org/10.3389/ fsurg.2015.00025.
8.
Kurup Harikrishnan KN, Bennett P Samuel, Joseph J Vettukattil: Expert Rev Cardiovasc Ther 2015, 13:1281.
Conflict of interest statement
9.
Leigh SJ, Bradley RJ, Purssell CP, Billson DR, Hutchins DA: PLoS One 2012, https://doi.org/10.1371/journal.pone.0049365.
Nothing declared.
10. Ambrosi A, Pumera M: Adv Funct Mater 2017:1700655.
Acknowledgements This work was supported by the project Advanced Functional Nanorobots (reg. No. CZ.02.1.01/0.0/0.0/15_003/0000444 financed by the EFRR).
References Papers of particular interest, published within the period of review, have been highlighted as: * * of outstanding interest 1.
Kwok SW, Goh KHH, Tan ZD, Tan STM, Tjiu WW, Soh JY, Ng ZJG, Chan YZ, Hui HK, Goh KEJ: Appl Mater Today 2017, 9: 167.
2.
Cheng TS, Nasir MZM, Ambrosi A, Pumera M: Appl Mater Today 2017, 9:212.
3.
Ambrosi A, Pumera M: Chem Soc Rev 2016, 45:2740.
4.
Lee J-Y, An J, Chua CK: Appl Mater Today 2017, 7:120.
5.
Goulas A, Binner JGP, Harris RA, Friel RJ: Appl Mater Today 2017, 6:54.
Current Opinion in Electrochemistry 2019, 14:133–137
11. Loo AH, Chua CK, Pumera M: DNA biosensing with 3D printing * * technology. Analyst 2017, 142:279. First 3D printed electrochemical biosensor 12. Liyarita BR, Ambrosi A, Pumera M: Electroanalysis 2018, 30:1319. 13. Ho EHZ, Ambrosi A, Pumera M: Appl Mater Today 2018, 12:43. 14. Manzanares Palenzuela CLM, Novotny F, Krupicka P, Sofer Z, Pumera M: Anal Chem 2018, 90:5753. 15. Browne Michelle P, Novotny Filip, Sofer Zdenek, Pumera Martin: ACS Appl Mater Interfaces 2018, 10:40294. 16. Manzanares Palenzuela CL, Pumera M: ACS Appl Mater Interfaces 2018. in press. 17. Symes MD, Kitson PJ, Yan J, Richmond CJ, Cooper GJT, * * Bowman RW, Vilbrandt T, Cronin L: Integrated 3D-printed reactionware for chemical synthesis and analysis. Nat Chem 2012, 4:349. 18. Kitson PJ, Glatzel S, Chen W, Lin CG, Song Y-F, Cronin L: 3D * * printing of versatile reactionware for chemical synthesis. Nat Protoc 2016, 11:920. www.sciencedirect.com
3D printing for biomedical applications Pumera
One of the first articles on fabrication of chemical reaction ware by 3D printing 19. Ambrosi A, Pumera M: Self-contained polymer/metal 3D printed electrochemical platform for tailored water splitting. Adv Funct Mater 2017. https://doi.org/10.1002/adfm.201700655; 2017.
www.sciencedirect.com
137
20. Ambrosi A, Pumera M: Multimaterial 3D-printed water electrolyzer with earth-abundant electrodeposited catalysts. ACS Sustain Chem Eng 2018, 6:16968. 21. Chan HN, Tan MJA, Wu HK: Point-of-care testing: applications of 3D printing. Lab Chip 2017, 17:2713.
Current Opinion in Electrochemistry 2019, 14:133–137
ScienceDirect
Current Opinion in
Electrochemistry
Review Article
Three-dimensionally printed electrochemical systems for biomedical analytical applications Martin Pumeraa,b Abstract
Additive manufacturing (3D-printing) has revolutionized many areas of the manufacturing. Three-dimensional printing offers enormous potential to biomedical devices, including electroanalytical systems. The motivation for 3D printing is rapid prototyping and decentralized customizable fabrication of bioanalytical systems in the diverse and remote areas of the globe. We overview the recent trends and discuss the fabrication and applications of 3D printed polymer/carbon and metal electrodes and whole electrochemical systems for biomedical applications and DNA detection. We show that sky is the limit and envision whole analytical systems, including electronics, to be 3D printed in the future for diagnostics in the remote areas of the globe. Addresses a Center for the Advanced Functional Nanorobots, Department of Inorganic Chemistry, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague 6, Czech Republic b Future Energy and Innovation Laboratory, Central European Institute ova 656/123, of Technology, Brno University of Technology, Purkyn Brno, CZ-616 00, Czech Republic Corresponding author: Pumera, Martin (pumera.research@gmail. com)
Current Opinion in Electrochemistry 2019, 14:133–137
medicine and biomedical applications [6]. Threedimensionally printed structures created for on-demand use by medical doctors during surgeries caught attention of the professionals and public as well [7e9]. One of the very important subsections of 3D printing is biosensing devices. In this review, we wish to discuss detection of biomarkers, biologically active compounds, and DNA on the 3D printed electrochemical sensors and systems. 3D-printing of bioanalytical systems allows for tailored and decentralized fabrication of the devices. 3D-printing of electroanalytical systems needs to overcome many challenges. The material must be electrically conducting in the final form. It must have electroactive surface (this is a challenge in the case of polymer/graphene 3D printed structures), and the surface needs to have suitable electrochemical window (this may be an issue in the case of metal electrodes). In addition, the surface needs to be easy to functionalize with biorecognition elements, that is, DNA or protein. We will review all these challenges and present opportunities this technology and materials offer. We divide the review into two parts, discussion of distinctive properties of 3D printed metal and polymer electrodes, in the context of biomedical sensing applications.
This review comes from a themed issue on Bioelectrochemistry Edited by Elena Ferapontova and Miroslav Fotja
3D printed metal electrodes
For a complete overview see the Issue and the Editorial
3D-printing of metals requires significantly more expensive equipment than polymer filament printing. The metal is typically iron, steel, titanium, or aluminum. The iron-based 3D printed electrodes are the most economical, and they do not passivate; however, to create usable electrochemical reproducible surfaces, they need to be coated with another metal. This is typically done with gold via electrodeposition method (Fig. 1) [10].
Available online 11 February 2019 https://doi.org/10.1016/j.coelec.2019.02.001 2451-9103/© 2019 Published by Elsevier B.V.
Keywords Additive manufacturing, 3D printing, Biosensor, Electrochemistry, DNA, Medicine.
Introduction 3D-printing, or additive manufacturing, revolutionized many fields of materials science and engineering, ranging from nanofabrication of electronics [1], sensors [2], and energy devices [3] to 3D printing of the buildings on the Earth or on the Moon [4,5]. One of the very important areas of the 3D printing where the decentralized fabrication of on-demand and tailorable 3D structures find a great scope of applications is www.sciencedirect.com
The 3D printed helical electrode was coated with gold and functionalized with ssDNA probe with a terminal -SH group [11]. Target and noncomplementary ssDNA was introduced to investigate whether the 3D printed electrode can be used as biosensor, and methylene blue intercalator was used as a label (Fig. 2). In series of articles, we demonstrated that 3D printed metal electrodes are of high importance for the Current Opinion in Electrochemistry 2019, 14:133–137
134 Bioelectrochemistry
Figure 1
Current Opinion in Electrochemistry
Typical procedure of fabrication of 3D printed electrodes. From left to right: computer-assisted design, 3D printed electrode, and 3D printed electrode covered with appropriate metal for particular application. 3D, three-dimensionally. Reprinted with permission from Ambrosi and Pumera [10].
detection of drugs such as acetaminophen [12] and biomarkers such as dopamine [12], ascorbic acid, and uric acid [13]. All these required gold-coated iron electrodes.
Figure 2
3D printed carbon electrodes 3D-printing of polymer and graphene/polymer requires comparably cheap systems under the cost of 1000 EUR, but it poses another challenge. The 3D printed structures are conductive, but the surface of the structure is covered with a very thin layer of polymer and initially the electrochemical performance is poor. One needs to ‘activate’ the surface. This can be done by several ways. Dimethylformamide (DMF) can be used to dissolve the top protective layer of polymer and to expose graphene flakes in polymer/graphene 3D printed electrodes. Fig. 3 shows the difference of nonactivated and activated polylactic acid/graphene 3D printed electrode for the detection of ascorbic acid and other electrochemical probes [14]. Another way to activate the polymer/graphene electrode is to use electrochemical activation d via anodization (oxidation) potential [15]. This leads to highly active surfaces; however, it is preferable to combine this method with DMF chemical treatment for enhanced performance [16].
Conclusions & outlook 3D-printing allows to 3D print whole electrochemical systems, including the electrode, beaker, and lid or the whole flow system (Fig. 4) [17e19]. Such on-demand capability allows rapid prototyping and on-spot device Current Opinion in Electrochemistry 2019, 14:133–137
Current Opinion in Electrochemistry
Metal 3D printed electrodes for electrochemical DNA sensing. (a) Schematic representation of the biosensing protocol used. A DNA recognition element, -SH probe, was first covalently immobilized onto the gold-plated 3D printed helix electrode. Subsequently, a blocking step with MCH (not shown) was performed to cover up the remaining electrode surface. The modified electrode was then incubated with a DNA target for hybridization reaction. Finally, the electrode was exposed to methylene blue solution, and the methylene blue molecules intercalated into the double helix structure of the hybridized double-stranded DNA. (b) Histograms representing the methylene blue reduction peak current values obtained after hybridization with complementary or noncomplementary DNA targets. The amount of DNA targets used was 100 pmol. Error bars correspond to replicate experiments. The inset demonstrates the respective differential pulse voltammograms acquired. All measurements were performed in 20 mM Tris–HCl (pH 7.0) under ambient conditions. 3D, threedimensionally. Reprinted with permission from Loo et al. [11].
www.sciencedirect.com
www.sciencedirect.com Figure 3
Activation of polymer/graphene 3D printed electrodes via DMF. Cyclic voltammograms of 3D printed electrodes, ring and disc shaped (I and II, respectively), recorded for various redox probes (1 mM) at a scan rate of 100 mV s−1. (a) Ru(NH3)6Cl3. (b) Fc-COOH. (c) K3Fe(CN)6:K4Fe(CN)6. (d) FeCl3. (e) Ascorbic acid. See experimental conditions for more details. Dashed lines: nonactivated electrodes. Full lines: activated electrodes. 3D, three-dimensionally. Reprinted with permission from Manzanares Palenzuela et al. [14].
3D printing for biomedical applications Pumera 135
Current Opinion in Electrochemistry 2019, 14:133–137
Current Opinion in Electrochemistry
136 Bioelectrochemistry
Figure 4
Current Opinion in Electrochemistry
Power of 3D printing for electrochemical systems. All items shown, including metal electrodes, containers, etc. are 3D printed. 3D, three-dimensional. Reprinted with permission from Ambrosi and Pumera [10].
fabrication and utilization, which is important for decentralized medicine. 3D-printing of whole biomedical analytical systems (i.e. in flow analysis setup) [20] is the next step on the route to customized decentralized on-demand biomedical sensing and analysis [21].
6.
Hsieh C-T, Liao C-Y, Dai N-T, Tseng C-S, Yen BL, Hsu S-H: Appl Mater Today 2018, 12:330.
7.
Chae MP, Rozen WM, McMenamin PG, Findlay MW, Spychal RT, Hunter-Smith DJ: Front Surg 2015, 2:25, https://doi.org/10.3389/ fsurg.2015.00025.
8.
Kurup Harikrishnan KN, Bennett P Samuel, Joseph J Vettukattil: Expert Rev Cardiovasc Ther 2015, 13:1281.
Conflict of interest statement
9.
Leigh SJ, Bradley RJ, Purssell CP, Billson DR, Hutchins DA: PLoS One 2012, https://doi.org/10.1371/journal.pone.0049365.
Nothing declared.
10. Ambrosi A, Pumera M: Adv Funct Mater 2017:1700655.
Acknowledgements This work was supported by the project Advanced Functional Nanorobots (reg. No. CZ.02.1.01/0.0/0.0/15_003/0000444 financed by the EFRR).
References Papers of particular interest, published within the period of review, have been highlighted as: * * of outstanding interest 1.
Kwok SW, Goh KHH, Tan ZD, Tan STM, Tjiu WW, Soh JY, Ng ZJG, Chan YZ, Hui HK, Goh KEJ: Appl Mater Today 2017, 9: 167.
2.
Cheng TS, Nasir MZM, Ambrosi A, Pumera M: Appl Mater Today 2017, 9:212.
3.
Ambrosi A, Pumera M: Chem Soc Rev 2016, 45:2740.
4.
Lee J-Y, An J, Chua CK: Appl Mater Today 2017, 7:120.
5.
Goulas A, Binner JGP, Harris RA, Friel RJ: Appl Mater Today 2017, 6:54.
Current Opinion in Electrochemistry 2019, 14:133–137
11. Loo AH, Chua CK, Pumera M: DNA biosensing with 3D printing * * technology. Analyst 2017, 142:279. First 3D printed electrochemical biosensor 12. Liyarita BR, Ambrosi A, Pumera M: Electroanalysis 2018, 30:1319. 13. Ho EHZ, Ambrosi A, Pumera M: Appl Mater Today 2018, 12:43. 14. Manzanares Palenzuela CLM, Novotny F, Krupicka P, Sofer Z, Pumera M: Anal Chem 2018, 90:5753. 15. Browne Michelle P, Novotny Filip, Sofer Zdenek, Pumera Martin: ACS Appl Mater Interfaces 2018, 10:40294. 16. Manzanares Palenzuela CL, Pumera M: ACS Appl Mater Interfaces 2018. in press. 17. Symes MD, Kitson PJ, Yan J, Richmond CJ, Cooper GJT, * * Bowman RW, Vilbrandt T, Cronin L: Integrated 3D-printed reactionware for chemical synthesis and analysis. Nat Chem 2012, 4:349. 18. Kitson PJ, Glatzel S, Chen W, Lin CG, Song Y-F, Cronin L: 3D * * printing of versatile reactionware for chemical synthesis. Nat Protoc 2016, 11:920. www.sciencedirect.com
3D printing for biomedical applications Pumera
One of the first articles on fabrication of chemical reaction ware by 3D printing 19. Ambrosi A, Pumera M: Self-contained polymer/metal 3D printed electrochemical platform for tailored water splitting. Adv Funct Mater 2017. https://doi.org/10.1002/adfm.201700655; 2017.
www.sciencedirect.com
137
20. Ambrosi A, Pumera M: Multimaterial 3D-printed water electrolyzer with earth-abundant electrodeposited catalysts. ACS Sustain Chem Eng 2018, 6:16968. 21. Chan HN, Tan MJA, Wu HK: Point-of-care testing: applications of 3D printing. Lab Chip 2017, 17:2713.
Current Opinion in Electrochemistry 2019, 14:133–137