Smarter Chips, Safer Lives: Lab-on-a-chip Biosensors for Pharmacological Applications and Healthcare Transformation
Main Article Content
Abstract
Rapid advancements in industries like genetics, biotechnology, and medicine have raised the demand for chemical and biochemical analysis and led to the development of useful chip applications for the use of sophisticated equipment, labs, and traditional procedures. A new technique called lab-on-a-chip displays a miniature laboratory onto a tiny coin-sized chip. Reagent mixing, dilution, electrophoresis, separation, staining, and detection can all be accomplished on a sensor chip. One or several analyses are made possible by this sensor technology, which also produces high sensitivity, quick diagnostic times, improved process control, inexpensive fabrication costs, portability, and safety. The detection of drugs is currently being performed using lab-on-a-chip technology, which may accept a variety of biological and non-biological materials. A number of detection techniques were used by lab-on-a-chip devices, with immunoassays being most frequently used. The usage of real-world samples should be increased, validation should be enhanced, and practicality should be further examined in terms of providing information on cost, speed of analysis, and convenience of use. A wide variety of lab-on-a-chip techniques are already accessible, which suggests that these devices could be used as portable, quick, and affordable detection systems. Lab-on-a-chip systems can be utilised both within and outside of hospitals for clinical purposes. Numerous benefits were provided by Lab-on-a-chips over existing tests, including as the ability to do point-of-care diagnostics with minimal fluid volumes, the use of small quantities of costly chemicals and samples, controlled flow rate, short diffusion distance, fast mixing time, and inexpensive fabrication costs.
Keywords:
Sensor chips, toxic drugs, healthcare transformation, detection, pharmacological.
Article Details
How to Cite
TIWARI, Ida; SINGH, Ankit Kumar.
Smarter Chips, Safer Lives: Lab-on-a-chip Biosensors for Pharmacological Applications and Healthcare Transformation.
Medical Research Archives, [S.l.], v. 13, n. 3, mar. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6337>. Date accessed: 06 apr. 2025.
doi: https://doi.org/10.18103/mra.v3i3.6337.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Esch E, Bahinski A, Huh D. Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov. 2015;14:248-260.
2. UNODC U. Executive Summary, Conclusions and Policy Implications [Internet]. Bookl 1 Vienna, Austria United Nations. Published online 2018:1-34.
3. Wei F, Patel P, Liao W, et al. Electrochemical sensor for multiplex biomarkers detection. Clin Cancer Res. 2009;15(13):4446-4452. doi:10.1158/1078-0432.CCR-09-0050
4. Phan DTT, Wang X, Craver BM, et al. A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. Lab Chip. 2017;17(3):511-520. doi:10.1039/c6lc01422d
5. Chen H, Zheng J, Zhang X, Luo M, Wang Z, Qiao X. Surface desorption atmospheric pressure chemical ionization mass spectrometry for direct ambient sample analysis without toxic chemical contamination. J Mass Spectrom. 2007;42:1045-1056.
6. Leary PE, Kammrath BW, Lattman KJ, Beals GL. Deploying Portable Gas Chromatography–Mass Spectrometry (GC-MS) to Military Users for the Identification of Toxic Chemical Agents in Theater. Appl Spectrosc. 2019;73(8):841-858. doi:10.1177/0003702819849499
7. Darwish IA. Immunoassay Methods and their Applications in Pharmaceutical Analysis: Basic Methodology and Recent Advances. Int J Biomed Sci. 2006;2(3):217-235. doi:10.59566/ijbs.2006.2217
8. Parameswara Rao K, Rao MC. Spectrophotometric methods in the analysis of drugs in pure and dosage forms. Int J Chem Sci. 2016;14(4):2389-2396.
9. Gummadi S, Kommoju M. Colorimetric Approaches To Drug Analysis And Applications – A Review. Am J PharmTech Res. 2019;9(1):14-37. doi:10.46624/ajptr.2019.v9.i1.002
10. Neužil P, Giselbrecht S, Länge K, Huang TJ, Manz A. Revisiting lab-on-a-chip technology for drug discovery. Nat Rev Drug Discov. 2012;11(8): 620-632. doi:10.1038/nrd3799
11. Staicu CE, Jipa F, Axente E, Radu M, Radu BM, Sima F. Lab-on-a-chip platforms as tools for drug screening in neuropathologies associated with blood–brain barrier alterations. Biomolecules. 2021;11(6). doi:10.3390/biom11060916
12. Kuru Cİ, Ulucan-Karnak F, Akgöl S. Lab-on-a-chip sensors: recent trends and future applications. Fundam Sens Technol Princ Nov Des. Published online January 1, 2023:65-98. doi:10.1016/B978-0-323-88431-0.00012-0
13. Ricotta V, Yu Y, Clayton N, et al. A chip-based potentiometric sensor for a Zika virus diagnostic using 3D surface molecular imprinting. Analyst. 2019;144(14):4266-4280. doi:10.1039/c9an00580c
14. Lim YC, Kouzani AZ, Duan W. Lab-on-a-chip: a component view. Microsyst Technol. 2010; 16:1995-2015.
15. Denizli A. Molecular imprinting-based sensors : Lab-on-chip integration and biomedical applications. J Pharm Biomed Anal. 2023;225 (December 2022).
16. Mark D, Haeberle S, Roth G, Stetten F Von, Zengerle R. Microfluidic lab-on-a-chip platforms: Requirements, characteristics and applications. Chem Soc Rev. 2010;39(3):1153-1182.
doi:10.1039/b820557b
17. Romao VC, Martins SAM, Germano J, Cardoso FA, Cardoso S, Freitas PP. Lab-on-Chip Devices: Gaining Ground Losing Size. ACS Nano. 2017;11(11):10659-10664.
18. Fu YQ, Luo JK, Nguyen NT, et al. Advances in piezoelectric thin films for acoustic biosensors, acoustofluidics and lab-on-chip applications. Prog Mater Sci. 2017;89:31-91. doi:10.1016/J.PMATSC I.2017.04.006
19. Sengupta P, Khanra K, Chowdhury AR, Datta P. Lab-on-a-Chip Sensing Devices for Biomedical Applications. Elsevier Ltd; 2019. doi:10.1016/B978-0-08-102420-1.00004-2
20. Ai Y, Zhang F, Wang C, Xie R, Liang Q. Recent progress in lab-on-a-chip for pharmaceutical analysis and pharmacological/toxicological test. TrAC - Trends Anal Chem. 2019;117:215-230. doi:10.1016/j.trac.2019.06.026
21. Huang XJ, Choi YK. Chemical sensors based on nanostructured materials. Sensors Actuators B Chem. 2007;122(2):659-671. doi:10.1016/J.SNB.2 006.06.022
22. El-Ansary A, Faddah LM. Nanoparticles as biochemical sensors. Nanotechnol Sci Appl. 2010;3(1):65-76. doi:10.2147/NSA.S8199
23. Kim Y, Jeon Y, Na M, Hwang SJ, Yoon Y. Recent Trends in Chemical Sensors for Detecting Toxic Materials. Sensors. 2024;24(2). doi:10.3390/s 24020431
24. Cui F, Zhou Z, Zhou HS. Review—Measurement and Analysis of Cancer Biomarkers Based on Electrochemical Biosensors. J Electrochem Soc. 2020;167(3):037525. doi:10.1149/2.0252003jes
25. Chen YT, Lee YC, Lai YH, et al. Review of Integrated Optical Biosensors for Point-of-Care Applications. Biosensors. 2020;10(12):1-22. doi:10.3390/BIOS10120209
26. Azizipour N, Avazpour R, Rosenzweig DH, Sawan M. Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip. Micromachines. 2020;11(6):599.
27. Hong CC, Lin CC, Hong CL, Lin ZX, Chung MH, Hsieh PW. Handheld analyzer with on-chip molecularly-imprinted biosensors for electrical detection of propofol in plasma samples. Biosens Bioelectron. 2016;86:623-629. doi:10.1016/J.BIO S.2016.07.032
28. Ugolini GS, Cruz-Moreira D, Visone R, Redaelli A, Rasponi M. Microfabricated physiological models for in vitro drug screening applications. Micromachines. 2016;7(12). doi:10.3390/mi7120233
29. Wang H, Zhu W, Xu C, Su W, Li Z. Engineering organoids-on-chips for drug testing and evaluation. Metabolism. 2025;162:156065. doi:10.1016/J.METABOL.2024.156065
30. Wang H, Zhu W, Xu C, Su W, Li Z. Engineering organoids-on-chips for drug testing and evaluation. Metabolism. 2025;162(July 2024): 156065. doi:10.1016/j.metabol.2024.156065
31. Guber AE, Heckele M, Herrmann D, et al. Microfluidic lab-on-a-chip systems based on polymers—fabrication and application. Chem Eng J. 2004;101(1-3):447-453. doi:10.1016/J.CEJ.2004.0 1.016
32. Yilmaz B, Yilmaz F. Lab-on-a-Chip Technology and Its Applications. Omi Technol Bio-engineering Towar Improv Qual Life. 2018;1:145-153. doi:10.1016/B978-0-12-804659-3.00008-7
33. Whitesides G. The origins and the future of microfluidics. Nature. 2006;442:368-373.
34. Jovanovich S, Bogdan G, Belcinski R, et al. Developmental validation of a fully integrated sample-to-profile rapid human identification system for processing single-source reference buccal samples. Forensic Sci Int Genet. 2015;16:181-194. doi:10.1016/J.FSIGEN.2014.12.004
35. Hopwood AJ, Hurth C, Yang J, et al. Integrated Microfluidic System for Rapid Forensic DNA Analysis: Sample Collection to DNA Profile. Anal Chem. 2010;82(16):6991-6999.
36. Lee NY. Recent progress in lab-on-a-chip technology and its potential application to clinical diagnoses. Int Neurourol J. 2013;17(1):2-10. doi:10.5213/inj.2013.17.1.2
37. Ghallab YH, Ismail Y. CMOS Circuits and Systems for Lab‐on‐a‐Chip Applications. Intech Open. Published online 2016.
https://www.intechopen.com/books/advanced-biometric-technologies/liveness-detection-in-biometrics
38. Nielsen JB, Hanson RL, Almughamsi HM, Pang C, Fish TR, Woolley AT. Microfluidics: innovations in materials and their fabrication and functionalization. Anal Chem. 2020;92(1):150-168. doi:10.1021/acs.analchem.9b04986
39. Dkhar DS, Kumari R, Malode SJ, Shetti NP, Chandra P. Integrated lab-on-a-chip devices: Fabrication methodologies, transduction system for sensing purposes. J Pharm Biomed Anal. 2023;223(October 2022):115120. doi:10.1016/j.jp ba.2022.115120
40. Xu M, Obodo D, Yadavalli VK. The design, fabrication, and applications of flexible biosensing devices. Biosens Bioelectron. 2019;124-125:96-114. doi:10.1016/J.BIOS.2018.10.019
41. Singh AK, Jaiswal N, Tiwari I, Ahmad M, Silva SRP. Electrochemical biosensors based on in situ grown carbon nanotubes on gold microelectrode array fabricated on glass substrate for glucose determination. Microchim Acta. 2023;190(2). doi:10.1007/s00604-022-05626-6
42. Saylan Y, Denizli A. Molecularly imprinted polymer-based microfluidic systems for point-of-care applications. Micromachines. 2019;10(11). doi:10.3390/mi10110766
43. Luka G, Ahmadi A, Najjaran H, et al. Microfluidics integrated biosensors: A leading technology towards lab-on-A-chip and sensing applications. Sensors (Switzerland). 2015;15(12): 30011-30031. doi:10.3390/s151229783
44. Wang Z, Han T, Jeon TJ, Park S, Kim SM. Rapid detection and quantification of bacteria using an integrated micro/nanofluidic device. Sensors Actuators B Chem. 2013;178:683-688. doi:10.1016/J.SNB.2013.01.017
45. Liu KK, Wu RG, Chuang YJ, Khoo HS, Huang SH, Tseng FG. Microfluidic systems for biosensing. Sensors. 2010;10(7):6623-6661. doi:10.3390/s100706623
46. Breslauer DN, Lee PJ, Lee LP. Microfluidics-based systems biology. Mol Biosyst. 2006;2(2):97-112. doi:10.1039/b515632g
47. Weibel DB, Whitesides GM. Applications of microfluidics in chemical biology. Curr Opin Chem Biol. 2006;10(6):584-591. doi:10.1016/J.CBPA.200 6.10.016
48. Hong J, Edel JB, deMello AJ. Micro- and nanofluidic systems for high-throughput biological screening. Drug Discov Today. 2009;14(3-4):134-146. doi:10.1016/J.DRUDIS.2008.10.001
49. Lafleur JP, Jönsson A, Senkbeil S, Kutter JP. Recent advances in lab-on-a-chip for biosensing applications. Biosens Bioelectron. 2016;76:213-233. doi:10.1016/J.BIOS.2015.08.003
50. Jr. NSL, Bocková M, Adam P, Homola J. Biosensor Enhancement Using Grooved Micromixers: Part II, Experimental Studies. Anal Chem. 2015;87(11):5524-5530.
51. Jr. NSL, Homola J. Biosensor Enhancement Using Grooved Micromixers: Part I, Numerical Studies. Anal Chem. 2015;87(11):5516-5523.
52. Hub L, Systems CD. Lab-on-a-Chip : Miniaturizing Laboratory Processes. Lab-on-a-Chip: Miniaturizing and Automating Analysis for Lab and Field.
53. Pol R, Céspedes F, Gabriel D, Baeza M. Microfluidic lab-on-a-chip platforms for environmental monitoring. TrAC Trends Anal Chem. 2017;95:62-68. doi:10.1016/J.TRAC.2017.08.001
54. Jiang L, Li S, Zheng J, Li Y, Huang H. Recent progress in microfluidic models of the blood-brain barrier. Micromachines. 2019;10(6):1-20. doi:10.3390/mi10060375
55. Dhiman N, Kingshott P, Sumer H, Sharma CS, Rath SN. On-chip anticancer drug screening – Recent progress in microfluidic platforms to address challenges in chemotherapy. Biosens Bioelectron. 2019;137:236-254. doi:10.1016/J.BIOS.2019.02.070
56. Ishida S. Organs-on-a-chip: Current applications and consideration points for in vitro ADME-Tox studies. Drug Metab Pharmacokinet. 2018;33(1):49-54. doi:10.1016/J.DMPK.2018.01.003
57. Mitxelena-Iribarren O, Zabalo J, Arana S, Mujika M. Improved microfluidic platform for simultaneous multiple drug screening towards personalized treatment. Biosens Bioelectron. 2019; 123:237-243. doi:10.1016/J.BIOS.2018.09.001
58. Musteata FM. Pharmacokinetic Applications of Microdevices and Microsampling Techniques. Bioanalysis. 2009;1(1):171-185.
59. Sontheimer-Phelps A, Hassell BA, Ingber D. Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer. 2019;19:65-81.
60. Li L, Li Y, Shao Z, Luo G, Ding M, Liang Q. Simultaneous Assay of Oxygen-Dependent Cytotoxicity and Genotoxicity of Anticancer Drugs on an Integrated Microchip. Anal Chem. 2018;90 (20):11899-11907.
61. Benam K, Villenave R, Lucchesi C, et. al. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods. 2016;13:151-157.
62. Low LA, Tagle DA. Tissue chips-innovative tools for drug development and disease modeling. Lab Chip. 2017;17(18):3026-3036. doi:10.1039/c 7lc00462a
63. Ewart L, Fabre K, Chakilam A, et al. Navigating tissue chips from development to dissemination: A pharmaceutical industry perspective. Exp Biol Med. 2017;242(16):1579-1585. doi:10.1177/15353 70217715441
64. Chen Y, Gao D, Liu H, Lin S, Jiang Y. Drug cytotoxicity and signaling pathway analysis with three-dimensional tumor spheroids in a microwell-based microfluidic chip for drug screening. Anal Chim Acta. 2015;898:85-92. doi:10.1016/J.ACA.2 015.10.006
65. Shi-Ping Zhao, Ma Y, Lou Q, Zhu H, Bo Yang, Fang Q. Three-Dimensional Cell Culture and Drug Testing in a Microfluidic Sidewall-Attached Droplet Array. Anal Chem. 2017;89(19):10153-10157.
66. Wang Z, Liu Z, Li L, Al. E. Investigation into the hypoxia-dependent cytotoxicity of anticancer drugs under oxygen gradient in a microfluidic device. Microfluid Nanofluid. 2015;19:1271-1279.
67. Orbach SM, Less RR, Anjaney Kothari PR. In Vitro Intestinal and Liver Models for Toxicity Testing. ACS Biomater Sci Eng. 2017;9(3):1898-1910.
68. Dong R, Liu Y, Mou L, Deng J, Jiang X. Microfluidics-Based Biomaterials and Biodevices. Adv Mater. 2019;31(45):1-18. doi:10.1002/adma.2 01805033
69. Oddo A, Peng B, Tong Z, et al. Advances in Microfluidic Blood–Brain Barrier (BBB) Models. Trends Biotechnol. 2019;37(12):1295-1314. doi:10.1016/j.t ibtech.2019.04.006
70. Mastrangeli M, Millet S, Mummery C, et al. Building blocks for a European organ-on-chip roadmap. ALTEX. 2019;36(3):481-492. doi:10.1457 3/ALTEX.1905221
71. Mastrangeli M, Millet S, van den Eijnden-Van Raaij J. Organ-on-chip in development: Towards a roadmap for organs-on-chip. ALTEX. 2019;36(4): 650-668. doi:10.14573/altex.1908271
72. Chirra HD, Shao L, Ciaccio N, et al. Planar Microdevices for Enhanced In Vivo Retention and Oral Bioavailability of Poorly Permeable Drugs. Adv Healthc Mater. 2014;3(10):1648-1654. doi:10.1002/a dhm.201300676
73. Fontana F, Ferreira MPA, Correia A, Hirvonen J, Santos HA. Microfluidics as a cutting-edge technique for drug delivery applications. J Drug Deliv Sci Technol. 2016;34:76-87. doi:10.1016/J.JD DST.2016.01.010
74. Cavero I, Guillon JM, Holzgrefe HH. Human organotypic bioconstructs from organ-on-chip devices for human-predictive biological insights on drug candidates. Expert Opin Drug Saf. 2019;18 (8):651-677. doi:10.1080/14740338.2019.1634689
75. Sophia M. Orbach, Less RR, Anjaney Kothari PR. In Vitro Intestinal and Liver Models for Toxicity Testing. ACS Biomater Sci Eng. 2017;9(3):1898-1910.
76. Bein A, Shin W, Jalili-Firoozinezhad S, et al. Microfluidic Organ-on-a-Chip Models of Human Intestine. Cmgh. 2018;5(4):659-668. doi:10.1016/j.jc mgh.2017.12.010
77. Kim S, LesherPerez SC a., Kim BC hou. C, et al. Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip. Biofabrication. 2016;8(1):015021.
doi:10.1088/1758-5090/8/1/015021
78. Zhang YS, Arneri A, Bersini S, et al. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials. 2016;110:45-59. doi:10.1016/J.BIOM ATERIALS.2016.09.003
79. Lind JU, Busbee TA, Valentine AD, et al. Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing. Nat Mater. 2017;16(3):303-308. doi:10.1038/nmat4782
80. Oleaga C, Riu A, Rothemund S, et al. Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system. Biomaterials. 2018;182:176-190. doi:10.1016/J.BIOMATERIALS.2018.07.062
81. Theobald J, Ghanem A, Wallisch P, et al. Liver-Kidney-on-Chip to Study Toxicity of Drug Metabolites. ACS Biomater Sci Eng. 2018;4(1):78-89. doi:10.1021/acsbiomaterials.7b00417
82. Koo Y, Hawkins BT, Yun Y. Three-dimensional (3D) tetra-culture brain on chip platform for organophosphate toxicity screening. Sci Rep. 2018;8(1):1-7. doi:10.1038/s41598-018-20876-2
83. Isoherranen N, Madabushi R, Huang S-M. Emerging Role of Organ-on-a-Chip Technologies in Quantitative Clinical Pharmacology Evaluation. Clin Transl Sci. 2019;12:113-121.
84. Zhu J. Application of Organ-on-Chip in Drug Discovery. J Biosci Med. 2020;08(03):119-134. doi:10.4236/jbm.2020.83011
85. Ai Y, Zhang F, Wang C, Xie R, Liang Q. Recent progress in lab-on-a-chip for pharmaceutical analysis and pharmacological/toxicological test. TrAC Trends Anal Chem. 2019;117:215-230. doi:10.1016/J.TRAC.2019.06.026
86. Weinhart M, Hocke A, Hippenstiel S, Kurreck J, Hedtrich S. 3D organ models—Revolution in pharmacological research? Pharmacol Res. 2019; 139:446-451. doi:10.1016/J.PHRS.2018.11.002
87. Dkhar DS, Kumari R, Malode SJ, Shetti NP, Chandra P. Integrated lab-on-a-chip devices: Fabrication methodologies, transduction system for sensing purposes. J Pharm Biomed Anal. 2023; 223:115120. doi:10.1016/J.JPBA.2022.115120
2. UNODC U. Executive Summary, Conclusions and Policy Implications [Internet]. Bookl 1 Vienna, Austria United Nations. Published online 2018:1-34.
3. Wei F, Patel P, Liao W, et al. Electrochemical sensor for multiplex biomarkers detection. Clin Cancer Res. 2009;15(13):4446-4452. doi:10.1158/1078-0432.CCR-09-0050
4. Phan DTT, Wang X, Craver BM, et al. A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. Lab Chip. 2017;17(3):511-520. doi:10.1039/c6lc01422d
5. Chen H, Zheng J, Zhang X, Luo M, Wang Z, Qiao X. Surface desorption atmospheric pressure chemical ionization mass spectrometry for direct ambient sample analysis without toxic chemical contamination. J Mass Spectrom. 2007;42:1045-1056.
6. Leary PE, Kammrath BW, Lattman KJ, Beals GL. Deploying Portable Gas Chromatography–Mass Spectrometry (GC-MS) to Military Users for the Identification of Toxic Chemical Agents in Theater. Appl Spectrosc. 2019;73(8):841-858. doi:10.1177/0003702819849499
7. Darwish IA. Immunoassay Methods and their Applications in Pharmaceutical Analysis: Basic Methodology and Recent Advances. Int J Biomed Sci. 2006;2(3):217-235. doi:10.59566/ijbs.2006.2217
8. Parameswara Rao K, Rao MC. Spectrophotometric methods in the analysis of drugs in pure and dosage forms. Int J Chem Sci. 2016;14(4):2389-2396.
9. Gummadi S, Kommoju M. Colorimetric Approaches To Drug Analysis And Applications – A Review. Am J PharmTech Res. 2019;9(1):14-37. doi:10.46624/ajptr.2019.v9.i1.002
10. Neužil P, Giselbrecht S, Länge K, Huang TJ, Manz A. Revisiting lab-on-a-chip technology for drug discovery. Nat Rev Drug Discov. 2012;11(8): 620-632. doi:10.1038/nrd3799
11. Staicu CE, Jipa F, Axente E, Radu M, Radu BM, Sima F. Lab-on-a-chip platforms as tools for drug screening in neuropathologies associated with blood–brain barrier alterations. Biomolecules. 2021;11(6). doi:10.3390/biom11060916
12. Kuru Cİ, Ulucan-Karnak F, Akgöl S. Lab-on-a-chip sensors: recent trends and future applications. Fundam Sens Technol Princ Nov Des. Published online January 1, 2023:65-98. doi:10.1016/B978-0-323-88431-0.00012-0
13. Ricotta V, Yu Y, Clayton N, et al. A chip-based potentiometric sensor for a Zika virus diagnostic using 3D surface molecular imprinting. Analyst. 2019;144(14):4266-4280. doi:10.1039/c9an00580c
14. Lim YC, Kouzani AZ, Duan W. Lab-on-a-chip: a component view. Microsyst Technol. 2010; 16:1995-2015.
15. Denizli A. Molecular imprinting-based sensors : Lab-on-chip integration and biomedical applications. J Pharm Biomed Anal. 2023;225 (December 2022).
16. Mark D, Haeberle S, Roth G, Stetten F Von, Zengerle R. Microfluidic lab-on-a-chip platforms: Requirements, characteristics and applications. Chem Soc Rev. 2010;39(3):1153-1182.
doi:10.1039/b820557b
17. Romao VC, Martins SAM, Germano J, Cardoso FA, Cardoso S, Freitas PP. Lab-on-Chip Devices: Gaining Ground Losing Size. ACS Nano. 2017;11(11):10659-10664.
18. Fu YQ, Luo JK, Nguyen NT, et al. Advances in piezoelectric thin films for acoustic biosensors, acoustofluidics and lab-on-chip applications. Prog Mater Sci. 2017;89:31-91. doi:10.1016/J.PMATSC I.2017.04.006
19. Sengupta P, Khanra K, Chowdhury AR, Datta P. Lab-on-a-Chip Sensing Devices for Biomedical Applications. Elsevier Ltd; 2019. doi:10.1016/B978-0-08-102420-1.00004-2
20. Ai Y, Zhang F, Wang C, Xie R, Liang Q. Recent progress in lab-on-a-chip for pharmaceutical analysis and pharmacological/toxicological test. TrAC - Trends Anal Chem. 2019;117:215-230. doi:10.1016/j.trac.2019.06.026
21. Huang XJ, Choi YK. Chemical sensors based on nanostructured materials. Sensors Actuators B Chem. 2007;122(2):659-671. doi:10.1016/J.SNB.2 006.06.022
22. El-Ansary A, Faddah LM. Nanoparticles as biochemical sensors. Nanotechnol Sci Appl. 2010;3(1):65-76. doi:10.2147/NSA.S8199
23. Kim Y, Jeon Y, Na M, Hwang SJ, Yoon Y. Recent Trends in Chemical Sensors for Detecting Toxic Materials. Sensors. 2024;24(2). doi:10.3390/s 24020431
24. Cui F, Zhou Z, Zhou HS. Review—Measurement and Analysis of Cancer Biomarkers Based on Electrochemical Biosensors. J Electrochem Soc. 2020;167(3):037525. doi:10.1149/2.0252003jes
25. Chen YT, Lee YC, Lai YH, et al. Review of Integrated Optical Biosensors for Point-of-Care Applications. Biosensors. 2020;10(12):1-22. doi:10.3390/BIOS10120209
26. Azizipour N, Avazpour R, Rosenzweig DH, Sawan M. Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip. Micromachines. 2020;11(6):599.
27. Hong CC, Lin CC, Hong CL, Lin ZX, Chung MH, Hsieh PW. Handheld analyzer with on-chip molecularly-imprinted biosensors for electrical detection of propofol in plasma samples. Biosens Bioelectron. 2016;86:623-629. doi:10.1016/J.BIO S.2016.07.032
28. Ugolini GS, Cruz-Moreira D, Visone R, Redaelli A, Rasponi M. Microfabricated physiological models for in vitro drug screening applications. Micromachines. 2016;7(12). doi:10.3390/mi7120233
29. Wang H, Zhu W, Xu C, Su W, Li Z. Engineering organoids-on-chips for drug testing and evaluation. Metabolism. 2025;162:156065. doi:10.1016/J.METABOL.2024.156065
30. Wang H, Zhu W, Xu C, Su W, Li Z. Engineering organoids-on-chips for drug testing and evaluation. Metabolism. 2025;162(July 2024): 156065. doi:10.1016/j.metabol.2024.156065
31. Guber AE, Heckele M, Herrmann D, et al. Microfluidic lab-on-a-chip systems based on polymers—fabrication and application. Chem Eng J. 2004;101(1-3):447-453. doi:10.1016/J.CEJ.2004.0 1.016
32. Yilmaz B, Yilmaz F. Lab-on-a-Chip Technology and Its Applications. Omi Technol Bio-engineering Towar Improv Qual Life. 2018;1:145-153. doi:10.1016/B978-0-12-804659-3.00008-7
33. Whitesides G. The origins and the future of microfluidics. Nature. 2006;442:368-373.
34. Jovanovich S, Bogdan G, Belcinski R, et al. Developmental validation of a fully integrated sample-to-profile rapid human identification system for processing single-source reference buccal samples. Forensic Sci Int Genet. 2015;16:181-194. doi:10.1016/J.FSIGEN.2014.12.004
35. Hopwood AJ, Hurth C, Yang J, et al. Integrated Microfluidic System for Rapid Forensic DNA Analysis: Sample Collection to DNA Profile. Anal Chem. 2010;82(16):6991-6999.
36. Lee NY. Recent progress in lab-on-a-chip technology and its potential application to clinical diagnoses. Int Neurourol J. 2013;17(1):2-10. doi:10.5213/inj.2013.17.1.2
37. Ghallab YH, Ismail Y. CMOS Circuits and Systems for Lab‐on‐a‐Chip Applications. Intech Open. Published online 2016.
https://www.intechopen.com/books/advanced-biometric-technologies/liveness-detection-in-biometrics
38. Nielsen JB, Hanson RL, Almughamsi HM, Pang C, Fish TR, Woolley AT. Microfluidics: innovations in materials and their fabrication and functionalization. Anal Chem. 2020;92(1):150-168. doi:10.1021/acs.analchem.9b04986
39. Dkhar DS, Kumari R, Malode SJ, Shetti NP, Chandra P. Integrated lab-on-a-chip devices: Fabrication methodologies, transduction system for sensing purposes. J Pharm Biomed Anal. 2023;223(October 2022):115120. doi:10.1016/j.jp ba.2022.115120
40. Xu M, Obodo D, Yadavalli VK. The design, fabrication, and applications of flexible biosensing devices. Biosens Bioelectron. 2019;124-125:96-114. doi:10.1016/J.BIOS.2018.10.019
41. Singh AK, Jaiswal N, Tiwari I, Ahmad M, Silva SRP. Electrochemical biosensors based on in situ grown carbon nanotubes on gold microelectrode array fabricated on glass substrate for glucose determination. Microchim Acta. 2023;190(2). doi:10.1007/s00604-022-05626-6
42. Saylan Y, Denizli A. Molecularly imprinted polymer-based microfluidic systems for point-of-care applications. Micromachines. 2019;10(11). doi:10.3390/mi10110766
43. Luka G, Ahmadi A, Najjaran H, et al. Microfluidics integrated biosensors: A leading technology towards lab-on-A-chip and sensing applications. Sensors (Switzerland). 2015;15(12): 30011-30031. doi:10.3390/s151229783
44. Wang Z, Han T, Jeon TJ, Park S, Kim SM. Rapid detection and quantification of bacteria using an integrated micro/nanofluidic device. Sensors Actuators B Chem. 2013;178:683-688. doi:10.1016/J.SNB.2013.01.017
45. Liu KK, Wu RG, Chuang YJ, Khoo HS, Huang SH, Tseng FG. Microfluidic systems for biosensing. Sensors. 2010;10(7):6623-6661. doi:10.3390/s100706623
46. Breslauer DN, Lee PJ, Lee LP. Microfluidics-based systems biology. Mol Biosyst. 2006;2(2):97-112. doi:10.1039/b515632g
47. Weibel DB, Whitesides GM. Applications of microfluidics in chemical biology. Curr Opin Chem Biol. 2006;10(6):584-591. doi:10.1016/J.CBPA.200 6.10.016
48. Hong J, Edel JB, deMello AJ. Micro- and nanofluidic systems for high-throughput biological screening. Drug Discov Today. 2009;14(3-4):134-146. doi:10.1016/J.DRUDIS.2008.10.001
49. Lafleur JP, Jönsson A, Senkbeil S, Kutter JP. Recent advances in lab-on-a-chip for biosensing applications. Biosens Bioelectron. 2016;76:213-233. doi:10.1016/J.BIOS.2015.08.003
50. Jr. NSL, Bocková M, Adam P, Homola J. Biosensor Enhancement Using Grooved Micromixers: Part II, Experimental Studies. Anal Chem. 2015;87(11):5524-5530.
51. Jr. NSL, Homola J. Biosensor Enhancement Using Grooved Micromixers: Part I, Numerical Studies. Anal Chem. 2015;87(11):5516-5523.
52. Hub L, Systems CD. Lab-on-a-Chip : Miniaturizing Laboratory Processes. Lab-on-a-Chip: Miniaturizing and Automating Analysis for Lab and Field.
53. Pol R, Céspedes F, Gabriel D, Baeza M. Microfluidic lab-on-a-chip platforms for environmental monitoring. TrAC Trends Anal Chem. 2017;95:62-68. doi:10.1016/J.TRAC.2017.08.001
54. Jiang L, Li S, Zheng J, Li Y, Huang H. Recent progress in microfluidic models of the blood-brain barrier. Micromachines. 2019;10(6):1-20. doi:10.3390/mi10060375
55. Dhiman N, Kingshott P, Sumer H, Sharma CS, Rath SN. On-chip anticancer drug screening – Recent progress in microfluidic platforms to address challenges in chemotherapy. Biosens Bioelectron. 2019;137:236-254. doi:10.1016/J.BIOS.2019.02.070
56. Ishida S. Organs-on-a-chip: Current applications and consideration points for in vitro ADME-Tox studies. Drug Metab Pharmacokinet. 2018;33(1):49-54. doi:10.1016/J.DMPK.2018.01.003
57. Mitxelena-Iribarren O, Zabalo J, Arana S, Mujika M. Improved microfluidic platform for simultaneous multiple drug screening towards personalized treatment. Biosens Bioelectron. 2019; 123:237-243. doi:10.1016/J.BIOS.2018.09.001
58. Musteata FM. Pharmacokinetic Applications of Microdevices and Microsampling Techniques. Bioanalysis. 2009;1(1):171-185.
59. Sontheimer-Phelps A, Hassell BA, Ingber D. Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer. 2019;19:65-81.
60. Li L, Li Y, Shao Z, Luo G, Ding M, Liang Q. Simultaneous Assay of Oxygen-Dependent Cytotoxicity and Genotoxicity of Anticancer Drugs on an Integrated Microchip. Anal Chem. 2018;90 (20):11899-11907.
61. Benam K, Villenave R, Lucchesi C, et. al. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods. 2016;13:151-157.
62. Low LA, Tagle DA. Tissue chips-innovative tools for drug development and disease modeling. Lab Chip. 2017;17(18):3026-3036. doi:10.1039/c 7lc00462a
63. Ewart L, Fabre K, Chakilam A, et al. Navigating tissue chips from development to dissemination: A pharmaceutical industry perspective. Exp Biol Med. 2017;242(16):1579-1585. doi:10.1177/15353 70217715441
64. Chen Y, Gao D, Liu H, Lin S, Jiang Y. Drug cytotoxicity and signaling pathway analysis with three-dimensional tumor spheroids in a microwell-based microfluidic chip for drug screening. Anal Chim Acta. 2015;898:85-92. doi:10.1016/J.ACA.2 015.10.006
65. Shi-Ping Zhao, Ma Y, Lou Q, Zhu H, Bo Yang, Fang Q. Three-Dimensional Cell Culture and Drug Testing in a Microfluidic Sidewall-Attached Droplet Array. Anal Chem. 2017;89(19):10153-10157.
66. Wang Z, Liu Z, Li L, Al. E. Investigation into the hypoxia-dependent cytotoxicity of anticancer drugs under oxygen gradient in a microfluidic device. Microfluid Nanofluid. 2015;19:1271-1279.
67. Orbach SM, Less RR, Anjaney Kothari PR. In Vitro Intestinal and Liver Models for Toxicity Testing. ACS Biomater Sci Eng. 2017;9(3):1898-1910.
68. Dong R, Liu Y, Mou L, Deng J, Jiang X. Microfluidics-Based Biomaterials and Biodevices. Adv Mater. 2019;31(45):1-18. doi:10.1002/adma.2 01805033
69. Oddo A, Peng B, Tong Z, et al. Advances in Microfluidic Blood–Brain Barrier (BBB) Models. Trends Biotechnol. 2019;37(12):1295-1314. doi:10.1016/j.t ibtech.2019.04.006
70. Mastrangeli M, Millet S, Mummery C, et al. Building blocks for a European organ-on-chip roadmap. ALTEX. 2019;36(3):481-492. doi:10.1457 3/ALTEX.1905221
71. Mastrangeli M, Millet S, van den Eijnden-Van Raaij J. Organ-on-chip in development: Towards a roadmap for organs-on-chip. ALTEX. 2019;36(4): 650-668. doi:10.14573/altex.1908271
72. Chirra HD, Shao L, Ciaccio N, et al. Planar Microdevices for Enhanced In Vivo Retention and Oral Bioavailability of Poorly Permeable Drugs. Adv Healthc Mater. 2014;3(10):1648-1654. doi:10.1002/a dhm.201300676
73. Fontana F, Ferreira MPA, Correia A, Hirvonen J, Santos HA. Microfluidics as a cutting-edge technique for drug delivery applications. J Drug Deliv Sci Technol. 2016;34:76-87. doi:10.1016/J.JD DST.2016.01.010
74. Cavero I, Guillon JM, Holzgrefe HH. Human organotypic bioconstructs from organ-on-chip devices for human-predictive biological insights on drug candidates. Expert Opin Drug Saf. 2019;18 (8):651-677. doi:10.1080/14740338.2019.1634689
75. Sophia M. Orbach, Less RR, Anjaney Kothari PR. In Vitro Intestinal and Liver Models for Toxicity Testing. ACS Biomater Sci Eng. 2017;9(3):1898-1910.
76. Bein A, Shin W, Jalili-Firoozinezhad S, et al. Microfluidic Organ-on-a-Chip Models of Human Intestine. Cmgh. 2018;5(4):659-668. doi:10.1016/j.jc mgh.2017.12.010
77. Kim S, LesherPerez SC a., Kim BC hou. C, et al. Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip. Biofabrication. 2016;8(1):015021.
doi:10.1088/1758-5090/8/1/015021
78. Zhang YS, Arneri A, Bersini S, et al. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials. 2016;110:45-59. doi:10.1016/J.BIOM ATERIALS.2016.09.003
79. Lind JU, Busbee TA, Valentine AD, et al. Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing. Nat Mater. 2017;16(3):303-308. doi:10.1038/nmat4782
80. Oleaga C, Riu A, Rothemund S, et al. Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system. Biomaterials. 2018;182:176-190. doi:10.1016/J.BIOMATERIALS.2018.07.062
81. Theobald J, Ghanem A, Wallisch P, et al. Liver-Kidney-on-Chip to Study Toxicity of Drug Metabolites. ACS Biomater Sci Eng. 2018;4(1):78-89. doi:10.1021/acsbiomaterials.7b00417
82. Koo Y, Hawkins BT, Yun Y. Three-dimensional (3D) tetra-culture brain on chip platform for organophosphate toxicity screening. Sci Rep. 2018;8(1):1-7. doi:10.1038/s41598-018-20876-2
83. Isoherranen N, Madabushi R, Huang S-M. Emerging Role of Organ-on-a-Chip Technologies in Quantitative Clinical Pharmacology Evaluation. Clin Transl Sci. 2019;12:113-121.
84. Zhu J. Application of Organ-on-Chip in Drug Discovery. J Biosci Med. 2020;08(03):119-134. doi:10.4236/jbm.2020.83011
85. Ai Y, Zhang F, Wang C, Xie R, Liang Q. Recent progress in lab-on-a-chip for pharmaceutical analysis and pharmacological/toxicological test. TrAC Trends Anal Chem. 2019;117:215-230. doi:10.1016/J.TRAC.2019.06.026
86. Weinhart M, Hocke A, Hippenstiel S, Kurreck J, Hedtrich S. 3D organ models—Revolution in pharmacological research? Pharmacol Res. 2019; 139:446-451. doi:10.1016/J.PHRS.2018.11.002
87. Dkhar DS, Kumari R, Malode SJ, Shetti NP, Chandra P. Integrated lab-on-a-chip devices: Fabrication methodologies, transduction system for sensing purposes. J Pharm Biomed Anal. 2023; 223:115120. doi:10.1016/J.JPBA.2022.115120