Liquid chromatography is a prominent analytical technique in separation science and chemical analysis, applied across numerous fields of research and within industrial applications. Over the past few decades, there has been a growing interest in the miniaturization of this technique, which has been particularly enabled through new miniature and portable detection technologies for in-field, at-site, and point-of-need (collectively 'out-of-lab') analyses. Accordingly, significant advances have been made in recent years in the development of miniaturized liquid chromatography with photometric, electrochemical, and mass spectrometric detection, enabling the development of field-deployable and portable instruments for various applications. Herein, recent developments in the miniaturization of detection systems for inclusion within, and/or coupling with, portable liquid chromatographic systems, are reviewed in detail together with critical comments and expected future trends in this area.

Australian Centre for Research on Separation Science University of Tasmania Hobart Australia

Central European Institute of Technology Brno University of Technology Brno Czech Republic

Department of Analytical Chemistry Lorestan University Khoramabad Iran

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Gumustas M, Kurbanoglu S, Uslu B, Ozkan SA. UPLC versus HPLC on drug analysis: advantageous, applications and their validation parameters. Chromatographia 2013;76:1365-427. https://doi.org/10.1007/s10337-013-2477-8

Wu N, Lippert JA, Lee ML. Practical aspects of ultrahigh pressure capillary liquid chromatography. J Chromatogr A. 2001;911:1-12. https://doi.org/10.1016/S0021-9673(00)01188-2

Robards K, Haddad P, Jackson P. Principles and practice of modern chromatographic methods. Amsterdam: Academic, Elsevier; 1994.

Rahimi F, Chatzimichail S, Saifuddin A, Surman AJ, Taylor-Robinson SD, Salehi-Reyhani A. A review of portable high-performance liquid chromatography: the future of the field? Chromatographia 2020;83:1165-95. https://doi.org/10.1007/s10337-020-03944-6

Vasconcelos Soares Maciel E, de Toffoli AL, Sobieski E, Domingues Nazário CE, Lanças FM. Miniaturized liquid chromatography focusing on analytical columns and mass spectrometry: a review. Anal Chim Acta. 2020;1103:11-31. https://doi.org/10.1016/j.aca.2019.12.064

Mejía-Carmona K, Soares da Silva Burato J, Borsatto JVB, de Toffoli AL, Lanças FM. Miniaturization of liquid chromatography coupled to mass spectrometry: 1. Current trends on miniaturized LC columns. TrAC Trends Anal Chem. 2020;122:115735. https://doi.org/10.1016/j.trac.2019.115735

Vargas Medina DA, Maciel EVS, Lanças FM. Miniaturization of liquid chromatography coupled to mass spectrometry. 3. Achievements on chip-based LC-MS devices. TrAC Trends Anal Chem. 2020;131:116003. https://doi.org/10.1016/j.trac.2020.116003

Vargas Medina DA, Maciel EVS, de Toffoli AL, Lanças FM. Miniaturization of liquid chromatography coupled to mass spectrometry.: 2. Achievements on modern instrumentation for miniaturized liquid chromatography coupled to mass spectrometry. TrAC Trends Anal Chem. 2020;128:115910. https://doi.org/10.1016/j.trac.2020.115910

Hirata Y, Novotny M. Techniques of capillary liquid chromatography. J Chromatogr A. 1979;186:521-8. https://doi.org/10.1016/S0021-9673(00)95272-5

Sharma S, Tolley LT, Tolley HD, Plistil A, Stearns SD, Lee ML. Hand-portable liquid chromatographic instrumentation. J Chromatogr A. 2015;1421:38-47. https://doi.org/10.1016/j.chroma.2015.07.119

Islam MA, Mahbub P, Nesterenko PN, Paull B, Macka M. Prospects of pulsed amperometric detection in flow-based analytical systems - A review. Anal Chim Acta. 2019;1052:10-26. https://doi.org/10.1016/j.aca.2018.10.066

Jones K, Malcolme-Lawes DJ. High-performance ultraviolet absorption detector for liquid chromatography: I. Preliminary Experiments. J Chromatogr A. 1985;329:25-32. https://doi.org/10.1016/S0021-9673(01)81892-6

Macka M, Piasecki T, Dasgupta PK. Light-emitting diodes for analytical chemistry. Annu Rev Anal Chem. 2014;7:183-207. https://doi.org/10.1146/annurev-anchem-071213-020059

Cecil F, Zhang M, Guijt RM, Henderson A, Nesterenko PN, Paull B, et al. 3D printed LED based on-capillary detector housing with integrated slit. Anal Chim Acta. 2017;965:131-6. https://doi.org/10.1016/j.aca.2017.02.020

Lam SC, Gupta V, Haddad PR, Paull B. 3D Printed liquid cooling interface for a deep-UV-LED-based flow-through absorbance detector. Anal Chem. 2019;91:8795-800. https://doi.org/10.1021/acs.analchem.9b01335

Spilstead KB, Learey JJ, Doeven EH, Barbante GJ, Mohr S, Barnett NW, et al. 3D-printed and CNC milled flow-cells for chemiluminescence detection. Talanta. 2014;126:110-5. https://doi.org/10.1016/j.talanta.2014.03.047

Lace A, Byrne A, Bluett S, Malaquin L, Raimbault V, Courson R, et al. Ion chromatograph with three-dimensional printed absorbance detector for indirect ultraviolet absorbance detection of phosphate in effluent and natural waters. J Sep Sci. 2022;45:1042-50. https://doi.org/10.1002/jssc.202100897

Ellis PS, Lyddy-Meaney AJ, Worsfold PJ, McKelvie ID. Multi-reflection photometric flow cell for use in flow injection analysis of estuarine waters. Anal Chim Acta. 2003;499:81-9. https://doi.org/10.1016/S0003-2670(03)00682-2

Kraiczek KG, Mannion J, Post S, Tsupryk A, Raghunathan V, Brennen R, et al. Micromachined fused silica liquid core waveguide capillary flow cell. Anal Chem. 2016;88:1100-5. https://doi.org/10.1021/acs.analchem.5b03219

Dasgupta PK, Shelor CP, Kadjo AF, Kraiczek KG. Flow-cell-induced dispersion in flow-through absorbance detection systems: True column effluent peak variance. Anal Chem. 2018;90:2063-9. https://doi.org/10.1021/acs.analchem.7b04248

Li Y, Nesterenko PN, Stanley R, Paull B, Macka M. High sensitivity deep-UV LED-based z-cell photometric detector for capillary liquid chromatography. Anal Chim Acta. 2018;1032:197-202. https://doi.org/10.1016/j.aca.2018.06.005

Lam SC, Coates LJ, Hemida M, Gupta V, Haddad PR, Macka M, et al. Miniature and fully portable gradient capillary liquid chromatograph. Anal Chim Acta. 2020;1101:199-210. https://doi.org/10.1016/j.aca.2019.12.014

Dolan JW. UV detector problems. LC-GC N Am. 2014;32:404-9.

Dolan JW. How does it work? Part IV: ultraviolet detectors: detectors based on ultraviolet absorbance are the most common detectors in use for liquid chromatography. LC-GC N Am. 2016;34:534-8.

Hemida M, Coates LJ, Lam S, Gupta V, Macka M, Wirth H-J, et al. Miniature multiwavelength deep UV-LED-based absorption detection system for capillary LC. Anal Chem. 2020;92:13688-93. https://doi.org/10.1021/acs.analchem.0c03460

High-sensitivity detection cell for the agilent capillary electrophoresis system. Accessed June 1, 2023. https://www.agilent.com/cs/library/technicaloverviews/public/5989-9808EN.pdf

Moring SE, Reel RT, Van Soest REJ. Optical improvements of a Z-shaped cell for high-sensitivity UV absorbance detection in capillary electrophoresis. Anal Chem. 1993;65:3454-9.

Boring CB, Dasgupta PK. An affordable high-performance optical absorbance detector for capillary systems. Anal Chim Acta. 1997;342:123-32. https://doi.org/10.1016/S0003-2670(96)00571-5

Sestak J, Planeta J, Kahle V. Nanolitre-scale cell based on L-shaped silica capillary and optical fibre for absorption photometric detection in capillary liquid chromatography. Anal Chim Acta. 2019;1037:99-108.

Sestak J, Planeta J, Kahle V. Compact optical detector utilizing light emitting diodes, 50 nL Lshaped silica capillary cell and CCD spectrometer for simultaneousmulti-wavelength monitoring of absorbance and fluorescence in microcolumn liquid chromatography. Anal Chim Acta. 2020;1112:80-91.

Gogaľová Z, Planeta J, Sestak J. An improved design of the fused silica capillary flow cell for absorbance detection in microcolumn liquid chromatography. Anal. Chim. Acta. 2023;1238:340637.

Bui DA, Bomastyk B, Hauser PC. Absorbance detector based on a deep UV light emitting diode for narrow-column HPLC. J Sep Sci. 2013;36:3152-7. https://doi.org/10.1002/jssc.201300598

Sharma S, Tolley HD, Farnsworth PB, Lee ML. LED-based UV absorption detector with low detection limits for capillary liquid chromatography. Anal Chem. 2015;87:1381-6. https://doi.org/10.1021/ac504275m

Li Y, Nesterenko PN, Paull B, Stanley R, Macka M. Performance of a new 235 nm UV-LED-based on-capillary photometric detector. Anal Chem. 2016;88:12116-21. https://doi.org/10.1021/acs.analchem.6b02832

da Silveira Petruci JF, Liebetanz MG, Cardoso AA, Hauser PC. Absorbance detector for high performance liquid chromatography based on a deep-UV light-emitting diode at 235 nm. J Chromatogr A. 2017;1512:143-6. https://doi.org/10.1016/j.chroma.2017.07.029

Murray E, Li Y, Currivan SA, Moore B, Morrin A, Diamond D, et al. Miniaturized capillary ion chromatograph with UV light-emitting diode based indirect absorbance detection for anion analysis in potable and environmental waters. J Sep Sci. 2018;41:3224-31. https://doi.org/10.1002/jssc.201800495

Murray E, Roche P, Harrington K, McCaul M, Moore B, Morrin A, et al. Low cost 235 nm ultra-violet light-emitting diode-based absorbance detector for application in a portable ion chromatography system for nitrite and nitrate monitoring. J Chromatogr A. 2019;1603:8-14. https://doi.org/10.1016/j.chroma.2019.05.036

Lam SC, Coates LJ, Gupta V, Wirth H-J, Gooley AA, Haddad PR, et al. Ultraviolet absorbance detector based on a high output power 235 nm surface mounted device-type light-emitting diode. J Chromatogr A. 2020;1631:461540. https://doi.org/10.1016/j.chroma.2020.461540

Laleyan DA, Zhao S, Woo SY, Tran HN, Le HB, Szkopek T, et al., AlN/h-BN heterostructures for Mg dopant-free deep ultraviolet photonics. Nano Lett. 2017;17:3738-43. https://doi.org/10.1021/acs.nanolett.7b01068

Hauser PC, Rupasinghe TWT, Cates NE. A multi-wavelength photometer based on light-emitting diodes. Talanta. 1995;42:605-12. https://doi.org/10.1016/0039-9140(95)01455-K

Kraiczek KG, Bonjour R, Salvadé Y, Zengerle R. Highly flexible UV-Vis radiation sources and novel detection schemes for spectrophotometric HPLC detection. Anal Chem. 2014;86:1146-52. https://doi.org/10.1021/ac403146y

Xie X, Tolley LT, Truong TX, Tolley HD, Farnsworth PB, Lee ML. Dual-wavelength light-emitting diode-based ultraviolet absorption detector for nano-flow capillary liquid chromatography. J Chromatogr A. 2017;1523:242-7. https://doi.org/10.1016/j.chroma.2017.07.097

Bui DA, Kraiczek KG, Hauser PC. Molecular absorption measurements with an optical fibre coupled array of ultra-violet light-emitting diodes. Anal Chim Acta. 2017;986:95-100. https://doi.org/10.1016/j.aca.2017.07.007

Coates LJ, Gooley AA, Lam SC, Firme B, Haddad PR, Wirth HJ, et al. Compact capillary high performance liquid chromatography system for pharmaceutical on-line reaction monitoring. Anal Chim Acta. 2023;1247:340903. https://doi.org/10.1016/j.aca.2023.340903

Baram G, Grachev M, Komarova NEA, Perelroyzen M, Bolvanov YA, Kuzmin S, et al. Micro-column liquid chromatography with multi-wave-length photometric detection: I. The OB-4 micro-column liquid chromatograph. J Chromatogr A. 1983;264:69-90.

Chatzimichail S, Rahimi F, Saifuddin A, Surman AJ, Taylor-Robinson SD, Salehi-Reyhani A. Hand-portable HPLC with broadband spectral detection enables analysis of complex polycyclic aromatic hydrocarbon mixtures. Commun Chem. 2021;4:17. https://doi.org/10.1038/s42004-021-00457-7

Islam MA, Lam SC, Li Y, Atia MA, Mahbub P, Nesterenko PN, et al. Capillary gap flow cell as capillary-end electrochemical detector in flow-based analysis. Electrochim Acta. 2019;303:85-93. https://doi.org/10.1016/j.electacta.2019.02.026

Islam MA, Koreshkova AN, Gupta V, Lewis T, Macka M, Paull B, et al. Fast pulsed amperometric waveform for miniaturised flow-through electrochemical detection: Application in monitoring graphene oxide reduction. Electrochim Acta. 2019;328:135087. https://doi.org/10.1016/j.electacta.2019.135087

Islam MA, Atia MA, Macka M, Paull B, Mahbub P. Electrochemical characterisation of nanoparticulate zirconium dioxide-on-gold electrode for electrochemical detection in flow-based analytical systems. Electrochim Acta. 2019;318:61-8. https://doi.org/10.1016/j.electacta.2019.06.031

Zhang M, Chen A, Lu JJ, Cao C, Liu S. Monitoring gradient profile on-line in micro- and nano-high performance liquid chromatography using conductivity detection. J Chromatogr A. 2016;1460:68-73. https://doi.org/10.1016/j.chroma.2016.07.005

Kubáň P, Hauser PC. 20th anniversary of axial capacitively coupled contactless conductivity detection in capillary electrophoresis. TrAC Trends Anal Chem. 2018;102:311-21. https://doi.org/10.1016/j.trac.2018.03.007

Umapathi R, Ghoreishian SM, Sonwal S, Rani GM, Huh YS. Portable electrochemical sensing methodologies for on-site detection of pesticide residues in fruits and vegetables. Coord Chem Rev. 2022;453:214305.

Boring CB, Dasgupta PK, Sjögren A. Compact, field-portable capillary ion chromatograph. J Chromatogr A. 1998;804:45-54. https://doi.org/10.1016/S0021-9673(98)00139-3

Labtron Equipment, LPIC-A10. Accessed April 5, 2023. https://www.labtron.com/portable-ion-chromatograph/lpic-a10

Snyder DT, Pulliam CJ, Ouyang Z, Cooks RG. Miniature and fieldable mass spectrometers: Recent advances. Anal Chem. 2016;88:2-29. https://doi.org/10.1021/acs.analchem.5b03070

Gao L, Cooks RG, Ouyang Z. Breaking the pumping speed barrier in mass spectrometry: Discontinuous atmospheric pressure interface. Anal Chem. 2008;80:4026-32. https://doi.org/10.1021/ac800014v

Syms RRA, Wright S. MEMS mass spectrometers: the next wave of miniaturization. J Micromech Microeng. 2016;26:023001. https://doi.org/10.1088/0960-1317/26/2/023001

Hendricks PI, Dalgleish JK, Shelley JT, Kirleis MA, McNicholas MT, Li L, et al. Autonomous in situ analysis and real-time chemical detection using a backpack miniature mass spectrometer: Concept, instrumentation development, and performance. Anal Chem. 2014;86:2900-8. https://doi.org/10.1021/ac403765x

Gao L, Song Q, Patterson GE, Cooks RG, Ouyang Z. Handheld rectilinear ion trap mass spectrometer. Anal Chem. 2006;78:5994-6002. https://doi.org/10.1021/ac061144k

Sokol E, Noll RJ, Cooks RG, Beegle LW, Kim HI, Kanik I. Miniature mass spectrometer equipped with electrospray and desorption electrospray ionization for direct analysis of organics from solids and solutions. Int J Mass Spectrom. 2011;306:187-95. https://doi.org/10.1016/j.ijms.2010.10.019

Li L, Chen T-C, Ren Y, Hendricks PI, Cooks RG, Ouyang Z. Mini 12, miniature mass spectrometer for clinical and other applications-Introduction and characterization. Anal Chem. 2014;86:2909-16. https://doi.org/10.1021/ac403766c

Accessed March 22, 2023. https://www.bayspec.com/spectroscopy/portable-mass-spectrometer/

Accessed March 22, 2023. https://www.bayspec.com/spectroscopy/continuity-transportable-high-sensitivity-mass-spectrometer/

Meng X, Zhang X, Zhai Y, Xu W. Mini 2000: A robust miniature mass spectrometer with continuous atmospheric pressure interface. Instruments. 2018;2:2-9.

Malcolm A, Wright S, Syms RRA, Moseley RW, O'Prey S, Dash N, et al. A miniature mass spectrometer for liquid chromatography applications. Rapid Commun Mass Spectrom. 2011;25:3281-8. https://doi.org/10.1002/rcm.5230

Accessed March 22, 2023. https://www.knauer.net/en/4000-mid-mass-spectrometer-with-automated-sampling-unit/p24011

Accessed March 22, 2023. http://www.microsaic.com/products/the-mid-platform/

Accessed March 22, 2023. https://www.q-technologies.co.uk/aquamms

Accessed March 22, 2023. https://axcendcorp.com/

Accessed March 22, 2023. https://www.advion.com/products/expression-cms

Accessed March 22, 2023. https://www.waters.com/waters/en_US/ACQUITY-QDa-Mass-Detector-for-Chromatographic-Analysis/nav.htm?cid=134761404&locale=en_US

Accessed March 22, 2023. https://www.waters.com/waters/en_US/SQ-Detector-2%F8Single-Quadrupole-Detection/nav.htm?cid=134631584&locale=en_US

Accessed March 22, 2023. https://www.agilent.com/cs/library/sitepreparationchecklists/G6465-90006_Ultivo_SitePrepGuide.pdf

Wright S, Malcolm A, Wright C, O'Prey S, Crichton E, Dash N, et al. A microelectromechanical systems-enabled, miniature triple quadrupole mass spectrometer. Anal Chem. 2015;87:3115-22. https://doi.org/10.1021/acs.analchem.5b00311

Wu J, Zhang W, Ouyang Z. On-demand mass spectrometry analysis by miniature mass spectrometer. Anal Chem. 2021;93:6003-7. https://doi.org/10.1021/acs.analchem.1c00575

de Graaf EL, Altelaar AFM, van Breukelen B, Mohammed S, Heck AJR. Improving SRM assay development: A global comparison between triple quadrupole, ion trap, and higher energy CID peptide fragmentation spectra. J Proteome Res. 2011;10:4334-41. https://doi.org/10.1021/pr200156b

Paul W, Steinwedel H, Nautrforsch Z. A new mass spectrometer without a magnetic field. Phys. Sci. 1953;38:448-50.

Otagawa T, Stetter JR, Zaromb S. Portable liquid chromatograph for analysis of primary aromatic amines in coal-derived materials. J Chromatogr. 1986;360:252-9.

Baram GI. Portable liquid chromatograph for mobile laboratories I. Aims. J Chromatogr A. 1996;728:387-99. https://doi.org/10.1016/0021-9673(95)01271-0

Tulchinsky VM, St Angelo DE. A practical portable HPLC system-MINICHROM, a new generation for field HPLC. Field Anal Chem Technol. 1998;2:281-5. https://doi.org/10.1002/(SICI)1520-6521(1998)2:5<281::AID-FACT5>3.0.CO;2-V

PolyLC. Smart LifeLC. Accessed April 5, 2023. https://polylc.com/Downloads/Smart_LifeLC_Product_Data_Sheet-PolyLC_415nm.pdf

Sharma S, Plistil A, Simpson RS, Liu K, Farnsworth PB, Stearns SD, et al. Instrumentation for hand-portable liquid chromatography. J Chromatogr A. 2014;1327:80-9. https://doi.org/10.1016/j.chroma.2013.12.059

Zhao X, Xie X, Sharma S, Tolley LT, Plistil A, Barnett HE, et al. Compact ultrahigh-pressure nanoflow capillary liquid chromatograph. Anal Chem. 2017;89:807-12. https://doi.org/10.1021/acs.analchem.6b03575

Accessed March 22, 2023. https://www.vici.com/uhplc/TrueNano-HPLC.php

Foster SW, Xie X, Pham M, Peaden PA, Patil LM, Tolley LT, et al. Portable capillary liquid chromatography for pharmaceutical and illicit drug analysis. J Sep Sci. 2020;43:1623-7. https://doi.org/10.1002/jssc.201901276

Li Y, Dvořák M, Nesterenko PN, Stanley R, Nuchtavorn N, Krčmová LK, et al. Miniaturised medium pressure capillary liquid chromatography system with flexible open platform design using off-the-shelf microfluidic components. Anal Chim Acta. 2015;896:166-76. https://doi.org/10.1016/j.aca.2015.09.015

Ishida A, Fujii M, Fujimoto T, Sasaki S, Yanagisawa I, Tani H, et al. A portable liquid chromatograph with a battery-operated compact electroosmotic pump and a microfluidic chip device with a reversed phase packed column. Anal Sci. 2015;31:1163-9.

Lynch KB, Chen A, Yang Y, Lu JJ, Liu S. High-performance liquid chromatographic cartridge with gradient elution capability coupled with UV absorbance detector and mass spectrometer for peptide and protein analysis. J Sep Sci. 2017;40:2752-8. https://doi.org/10.1002/jssc.201700185

Chatzimichail S, Casey D, Salehi-Reyhani A. Zero electrical power pump for portable high-performance liquid chromatography. Analyst. 2019;144:6207-13. https://doi.org/10.1039/C9AN01302D

Coates LJ, Lam SC, Gooley AA, Haddad PR, Paull B, Wirth H-J. Modular, cost-effective, and portable capillary gradient liquid chromatography system for on-site analysis. J Chromatogr A. 2020;1626:461374. https://doi.org/10.1016/j.chroma.2020.461374

Hemida M, Haddad PR, Lam SC, Coates LJ, Riley F, Diaz A, et al. Compact capillary high performance liquid chromatography system for pharmaceutical on-line reaction monitoring. Anal Chim Acta. 2023;1247:340903. https://doi.org/10.1016/j.aca.2023.340903

Ponce-Rodríguez HD, Verdú-Andrés J, Herráez-Hernández R, Campíns-Falcó P. Exploring hand-portable nano-liquid chromatography for in place water analysis: Determination of trimethylxanthines as a use case. Sci Total Environ. 2020;747:140966. https://doi.org/10.1016/j.scitotenv.2020.140966

Hemida M, Ghiasvand A, Gupta V, Coates LJ, Gooley AA, Wirth H-J, et al. Small-footprint, field-deployable LC/MS system for on-site analysis of per- and polyfluoroalkyl substances in soil. Anal Chem. 2021;93:12032-40. https://doi.org/10.1021/acs.analchem.1c02193

Bluett S, O'Callaghan P, Paull B, Murray E. Robust off-grid analyser for autonomous remote in-situ monitoring of nitrate and nitrite in water. Talanta Open. 2023;7:100173. https://doi.org/10.1016/j.talo.2022.100173

Li Y, Dvořák M, Nesterenko PN, Nuchtavorn N, Macka M. High power deep UV-LEDs for analytical optical instrumentation. Sens Actuators B Chem. 2018;255:1238-43. https://doi.org/10.1016/j.snb.2017.08.085

Krčmová L, Stjernlof A, Mehlen S, Hauser PC, Abele S, Paull B, et al. Deep-UV-LEDs in photometric detection: A 255 nm LED on-capillary detector in capillary electrophoresis. Analyst. 2009;134:2394-6. https://doi.org/10.1039/B916081G

Bomastyk B, Petrovic I, Hauser PC. Absorbance detector for high-performance liquid chromatography based on light-emitting diodes for the deep-ultraviolet range. J Chromatogr A. 2011;1218:3750-6. https://doi.org/10.1016/j.chroma.2011.04.039