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Research Article| Volume 63, 102824, March 2023

Taking the microfluidic approach to nucleic acid analysis in forensics: Review and perspectives

Published:December 23, 2022DOI:https://doi.org/10.1016/j.fsigen.2022.102824

      Highlights

      • Tools that enable forensic human identification at the point-of-need have the potential to expedite investigations.
      • Forensic microfluidic technologies have unique advantages and practical limitations.
      • The research and development of automated methods to mimic forensic workflows have resulted in few commercial systems.
      • The integration of existing microfluidic platforms is discussed and opportunity zones for future innovation are proposed.

      Abstract

      Forensic laboratories are universally acknowledged as being overburdened, underfunded, and in need of improved analytical methods to expedite investigations, decrease the costs associated with nucleic acid (NA) analysis, and perform human identification (HID) at the point of need (e.g., crime scene, booking station, etc.). In response, numerous research and development (R&D) efforts have resulted in microfluidic tools that automate portions of the forensic genetic workflow, including DNA extraction, amplification, and short tandem repeat (STR) typing. By the early 2000 s, reports from the National Institute of Justice (NIJ) anticipated that microfluidic ‘swab-in-profile-out’ systems would be available for use at the crime scene by 2015 and the FBI’s 2010 ‘Rapid DNA’ Initiative, approved by Congress in 2017, directed this effort by guiding the development and implementation of maturing systems. At present, few fully-automated microfluidic DNA technologies are commercially available for forensic HID and their adoption by agencies interested in identification has been limited. In practice, the integration of complex laboratory processes to produce one autonomous unit, along with the highly variable nature of forensic input samples, resulted in systems that are more expensive per sample and not comparable to gold-standard identification methods in terms of sensitivity, reproducibility, and multiplex capability. This Review and Perspective provides insight into the contributing factors to this outcome; namely, we focus on the complications associated with the tremendous undertaking that is developing a sample-in-answer-out platform for HID. For context, we also describe the intricate forensic landscape that contributes to a nuanced marketplace, not easily distilled down to cases of simple supply and demand. Moving forward and considering the trade-offs associated with developing methods to compete, sometimes directly, with conventional ones, we recommend a focus shift for microfluidics developers toward the creation of innovative solutions for emerging applications in the field to increase the bandwidth of the forensic investigative toolkit. Likewise, we urge case working personnel to reframe how they conceptualize the currently available Rapid DNA tools; rather than comparing these microfluidic methods to gold-standard procedures, take advantage of their rapid and integrated modes for those situations requiring expedited identifications in an informed manner.

      Keywords

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      References

        • Niculescu A.-G.
        • Chircov C.
        • Bîrcă A.C.
        • Grumezescu A.M.
        Fabrication and applications of microfluidic devices: a review.
        IJMS. 2021; 22: 2011https://doi.org/10.3390/ijms22042011
        • Bruijns B.
        • van Asten A.
        • Tiggelaar R.
        • Gardeniers H.
        Microfluidic devices for forensic dna analysis: a review.
        Biosensors. 2016; 6: 41https://doi.org/10.3390/bios6030041
        • Carney C.
        • Whitney S.
        • Vaidyanathan J.
        • Persick R.
        • Noel F.
        • Vallone P.M.
        • Romsos E.L.
        • Tan E.
        • Grover R.
        • Turingan R.S.
        • French J.L.
        • Selden R.F.
        Developmental validation of the ANDE™ rapid DNA system with FlexPlex™ assay for arrestee and reference buccal swab processing and database searching.
        Forensic Sci. Int.: Genet. 2019; 40: 120-130https://doi.org/10.1016/j.fsigen.2019.02.016
        • Buscaino J.
        • Barican A.
        • Farrales L.
        • Goldman B.
        • Klevenberg J.
        • Kuhn M.
        • Lin F.
        • Nguyen P.
        • Salceda S.
        • Schueren R.
        • Smith C.
        • Troup C.
        • Tsou D.
        • Vangbo M.
        • King D.
        Evaluation of a rapid DNA process with the RapidHIT® ID system using a specialized cartridge for extracted and quantified human DNA.
        Forensic Sci. Int.: Genet. 2018; 34: 116-127https://doi.org/10.1016/j.fsigen.2018.02.010
        • Kobus H.
        • Houck M.
        • Speaker P.
        • Riley R.
        • Witt T.
        Managing performance in the forensic sciences: expectations in light of limited budgets.
        Forensic Sci. Policy Manag.: Int. J. 2011; 2: 36-43https://doi.org/10.1080/19409044.2011.564271
        • Dror I.E.
        Practical solutions to cognitive and human factor challenges in forensic science.
        Forensic Sci. Policy Manag.: Int. J. 2013; 4: 105-113https://doi.org/10.1080/19409044.2014.901437
      1. Future of Forensic DNA Testing: Predictions of the Research and Development Working Group, National Institute of Justice, 2000. 〈https://nij.ojp.gov/library/publications/future-forensic-dna-testing-predictions-research-and-development-working-group〉.

        • Butler J.M.
        • Willis S.
        Interpol review of forensic biology and forensic DNA typing 2016-2019.
        Forensic Sci. Int.: Synerg. 2020; 2: 352-367https://doi.org/10.1016/j.fsisyn.2019.12.002
        • Butler J.M.
        Advanced Topics in Forensic DNA Typing: Methodology.
        Elsevier/Academic Press,, Walthan, MA2012
        • Hares D.R.
        • Kneppers A.
        • Onorato A.J.
        • Kahn S.
        Rapid DNA for crime scene use: Enhancements and data needed to consider use on forensic evidence for State and National DNA Databasing – An agreed position statement by ENFSI, SWGDAM and the Rapid DNA Crime Scene Technology Advancement Task Group.
        Forensic Sci. Int.: Genet. 2020; 48102349https://doi.org/10.1016/j.fsigen.2020.102349
        • Chiu D.T.
        • deMello A.J.
        • Di Carlo D.
        • Doyle P.S.
        • Hansen C.
        • Maceiczyk R.M.
        • Wootton R.C.R.
        Small but perfectly formed? Successes, challenges, and opportunities for microfluidics in the chemical and biological sciences.
        Chem. 2017; 2: 201-223https://doi.org/10.1016/j.chempr.2017.01.009
        • Mark D.
        • Haeberle S.
        • Roth G.
        • von Stetten F.
        • Zengerle R.
        Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications.
        Chem. Soc. Rev. 2010; 39: 1153https://doi.org/10.1039/b820557b
        • Kellner M.J.
        • Ross J.J.
        • Schnabl J.
        • Dekens M.P.S.
        • Heinen R.
        • Grishkovskaya I.
        • Bauer B.
        • Stadlmann J.
        • Menéndez-Arias L.
        • Fritsche-Polanz R.
        • Traugott M.
        • Seitz T.
        • Zoufaly A.
        • Födinger M.
        • Wenisch C.
        • Zuber J.
        Vienna Covid-19 Diagnostics Initiative (VCDI), A. Pauli, J. Brennecke, A rapid, highly sensitive and open-access SARS-CoV-2 detection assay for laboratory and home testing.
        Mol. Biol. 2020; https://doi.org/10.1101/2020.06.23.166397
        • Mukhopadhyay R.
        Microfluidics: on the slope of enlightenment.
        Anal. Chem. 2009; 81: 4169-4173https://doi.org/10.1021/ac900638w
        • Dedehayir O.
        • Steinert M.
        The hype cycle model: a review and future directions.
        Technol. Forecast. Soc. Change. 2016; 108: 28-41https://doi.org/10.1016/j.techfore.2016.04.005
        • Manz A.
        • Harrison D.J.
        • Verpoorte E.M.J.
        • James.C. Fettinger A.
        • Paulus H.
        • Lüdi H.M.
        • Widmer
        Planar chips technology for miniaturization and integration of separation techniques into monitoring systems.
        J. Chromatogr. A. 1992; 593: 253-258https://doi.org/10.1016/0021-9673(92)80293-4
        • Manz A.
        • Verpoorte E.
        • Raymond D.E.
        • Effenhauser C.S.
        • Burggraf N.
        • Widmer H.M.
        µ-TAS: Miniaturized total chemical analysis systems.
        in: Van den Berg A. Bergveld P. Micro Total Analysis Systems. Springer, Netherlands, Dordrecht1995: 5-27
        • Whitesides G.M.
        The origins and the future of microfluidics.
        Nature. 2006; 442: 368-373https://doi.org/10.1038/nature05058
        • Zhang P.
        • Bachman H.
        • Ozcelik A.
        • Huang T.J.
        Acoustic microfluidics.
        Annu. Rev. Anal. Chem. 2020; 13: 17-43https://doi.org/10.1146/annurev-anchem-090919-102205
        • Strohmeier O.
        • Keller M.
        • Schwemmer F.
        • Zehnle S.
        • Mark D.
        • von Stetten F.
        • Zengerle R.
        • Paust N.
        Centrifugal microfluidic platforms: advanced unit operations and applications.
        Chem. Soc. Rev. 2015; 44: 6187-6229https://doi.org/10.1039/C4CS00371C
        • Zhang X.
        • Xia K.
        • Ji A.
        A portable plug-and-play syringe pump using passive valves for microfluidic applications.
        Sens. Actuators B: Chem. 2020; 304127331https://doi.org/10.1016/j.snb.2019.127331
        • Duffy D.C.
        • McDonald J.C.
        • Schueller O.J.A.
        • Whitesides G.M.
        Rapid prototyping of microfluidic systems in poly(dimethylsiloxane.
        Anal. Chem. 1998; 70: 4974-4984https://doi.org/10.1021/ac980656z
        • Liu K.
        • Fan Z.H.
        Thermoplastic microfluidic devices and their applications in protein and DNA analysis.
        Analyst. 2011; 136: 1288https://doi.org/10.1039/c0an00969e
        • Faustino V.
        • Catarino S.O.
        • Lima R.
        • Minas G.
        Biomedical microfluidic devices by using low-cost fabrication techniques: a review.
        J. Biomech. 2016; 49: 2280-2292https://doi.org/10.1016/j.jbiomech.2015.11.031
      2. Landers J.P. Handbook of Capillary and Microchip Electrophoresis and Associated Microtechniques. 3rd ed.,. CRC Press, Boca Raton2008
        • Emrich C.A.
        • Tian H.
        • Medintz I.L.
        • Mathies R.A.
        Microfabricated 384-lane capillary array electrophoresis bioanalyzer for ultrahigh-throughput genetic analysis.
        Anal. Chem. 2002; 74: 5076-5083https://doi.org/10.1021/ac020236g
        • Unger M.A.
        • Chou H.-P.
        • Thorsen T.
        • Scherer A.
        • Quake S.R.
        Monolithic microfabricated valves and pumps by multilayer soft lithography.
        Science. 2000; 288: 113-116https://doi.org/10.1126/science.288.5463.113
        • Grover W.H.
        • Ivester R.H.C.
        • Jensen E.C.
        • Mathies R.A.
        Development and multiplexed control of latching pneumatic valves using microfluidic logical structures.
        Lab Chip. 2006; 6: 623https://doi.org/10.1039/b518362f
        • Thorsen T.
        • Maerkl S.J.
        • Quake S.R.
        Microfluidic large-scale integration.
        Science. 2002; 298: 580-584https://doi.org/10.1126/science.1076996
      3. Laboratory Division Biometrics Analysis Section, Guide to All Things Rapid DNA, U. S. Department of Justice Federal Bureau of Investigation Science and Technology Branch, 2022. 〈http://www.lsp.org/pdf/FBI_Guide_to_All_Things_Rapid_DNA_01_27_2022.pdf〉.

      4. Quality Assurance Standards for Forensic DNA Testing Laboratories, Federal Bureau of Investigation, 2011. 〈https://ucr.fbi.gov/lab/biometric-analysis/codis/quality-assurance-standards-for-forensic-dna-testing-laboratories〉.

      5. James F. Sensenbrenner Jr., Rapid DNA Act of 2017, 2017. 〈https://www.congress.gov/bill/115th-congress/house-bill/510〉.

      6. Non-CODIS Rapid DNA Considerations and Best Practices for Law Enforcement Use, Federal Bureau of Investigation, Non-CODIS Rpaid DNA Best Practices/Outreach and Courtroom Considerrations Task Group, 2019. 〈https://le.fbi.gov/file-repository/non-codis-rapid-dna-best-practices-092419.pdf/view〉.

        • Klapperich C.M.
        Microfluidic diagnostics: time for industry standards.
        Expert Rev. Med. Devices. 2009; 6: 211-213https://doi.org/10.1586/erd.09.11
        • Reyes D.R.
        • van Heeren H.
        Proceedings of the first workshop on standards for microfluidics.
        J. Res. Natl. Inst. Stan. 2019; 124124001https://doi.org/10.6028/jres.124.001
        • Reyes D.R.
        • van Heeren H.
        • Guha S.
        • Herbertson L.
        • Tzannis A.P.
        • Ducrée J.
        • Bissig H.
        • Becker H.
        Accelerating innovation and commercialization through standardization of microfluidic-based medical devices.
        Lab Chip. 2021; 21: 9-21https://doi.org/10.1039/D0LC00963F
        • Kim J.
        • Johnson M.
        • Hill P.
        • Gale B.K.
        Microfluidic sample preparation: cell lysis and nucleic acid purification.
        Integr. Biol. 2009; 1: 574https://doi.org/10.1039/b905844c
        • Dineva M.A.
        • Mahilum-Tapay L.
        • Lee H.
        Sample preparation: a challenge in the development of point-of-care nucleic acid-based assays for resource-limited settings.
        Analyst. 2007; 132: 1193https://doi.org/10.1039/b705672a
        • Wen J.
        • Legendre L.A.
        • Bienvenue J.M.
        • Landers J.P.
        Purification of nucleic acids in microfluidic devices.
        Anal. Chem. 2008; 80: 6472-6479https://doi.org/10.1021/ac8014998
        • Chong K.W.Y.
        • Thong Z.
        • Syn C.K.
        Recent trends and developments in forensic DNA extraction.
        WIREs Forensic Sci. 2021; 3https://doi.org/10.1002/wfs2.1395
        • Gin K.
        • Tovar J.
        • Bartelink E.J.
        • Kendell A.
        • Milligan C.
        • Willey P.
        • Wood J.
        • Tan E.
        • Turingan R.S.
        • Selden R.F.
        The 2018 California wildfires: integration of rapid DNA to dramatically accelerate victim identification.
        J. Forensic Sci. 2020; 65: 791-799https://doi.org/10.1111/1556-4029.14284
        • Turingan R.S.
        • Tan E.
        • Jiang H.
        • Brown J.
        • Estari Y.
        • Krautz‐Peterson G.
        • Selden R.F.
        Developmental validation of the ANDE 6C system for rapid DNA analysis of forensic casework and DVI samples.
        J. Forensic Sci. 2020; 65: 1056-1071https://doi.org/10.1111/1556-4029.14286
        • Murakami C.
        • Irie W.
        • Sasaki C.
        • Nakamaru N.
        • Sakamoto M.
        • Nagato J.
        • Satoh F.
        Individual identification using the RapidHIT™ ID system for forensic samples.
        Leg. Med. 2020; 47101776https://doi.org/10.1016/j.legalmed.2020.101776
        • Kutter J.P.
        • Jacobson S.C.
        • Ramsey J.M.
        Solid phase extraction on microfluidic devices.
        J. Micro Sep. 2000; 12: 93-97https://doi.org/10.1002/(SICI)1520-667X(2000)12:2<93::AID-MCS5>3.0.CO;2-P
        • Clark C.
        • Turiello R.
        • Cotton R.
        • Landers J.P.
        Analytical approaches to differential extraction for sexual assault evidence.
        Anal. Chim. Acta. 2020; (S0003267020307972)https://doi.org/10.1016/j.aca.2020.07.059
        • Vuichard S.
        • Borer U.
        • Bottinelli M.
        • Cossu C.
        • Malik N.
        • Meier V.
        • Gehrig C.
        • Sulzer A.
        • Morerod M.-L.
        • Castella V.
        Differential DNA extraction of challenging simulated sexual-assault samples: a Swiss collaborative study.
        Invest. Genet. 2011; 2: 11https://doi.org/10.1186/2041-2223-2-11
        • Inci F.
        • Ozen M.O.
        • Saylan Y.
        • Miansari M.
        • Cimen D.
        • Dhara R.
        • Chinnasamy T.
        • Yuksekkaya M.
        • Filippini C.
        • Kumar D.K.
        • Calamak S.
        • Yesil Y.
        • Durmus N.G.
        • Duncan G.
        • Klevan L.
        • Demirci U.
        A novel on-chip method for differential extraction of sperm in forensic cases.
        Adv. Sci. 2018; 5: 1800121https://doi.org/10.1002/advs.201800121
        • Horsman K.M.
        • Barker S.L.R.
        • Ferrance J.P.
        • Forrest K.A.
        • Koen K.A.
        • Landers J.P.
        Separation of sperm and epithelial cells in a microfabricated device: potential application to forensic analysis of sexual assault evidence.
        Anal. Chem. 2005; 77: 742-749https://doi.org/10.1021/ac0486239
        • Liu W.
        • Chen W.
        • Liu R.
        • Ou Y.
        • Liu H.
        • Xie L.
        • Lu Y.
        • Li C.
        • Li B.
        • Cheng J.
        Separation of sperm and epithelial cells based on the hydrodynamic effect for forensic analysis.
        Biomicrofluidics. 2015; 9044127https://doi.org/10.1063/1.4928453
        • Norris J.V.
        • Evander M.
        • Horsman-Hall K.M.
        • Nilsson J.
        • Laurell T.
        • Landers J.P.
        Acoustic differential extraction for forensic analysis of sexual assault evidence.
        Anal. Chem. 2009; 81: 6089-6095https://doi.org/10.1021/ac900439b
        • Clark C.P.
        • Xu K.
        • Scott O.
        • Hickey J.
        • Tsuei A.-C.
        • Jackson K.
        • Landers J.P.
        Acoustic trapping of sperm cells from mock sexual assault samples.
        Forensic Sci. Int.: Genet. 2019; 41: 42-49https://doi.org/10.1016/j.fsigen.2019.03.012
        • Auka N.
        • Valle M.
        • Cox B.D.
        • Wilkerson P.D.
        • Dawson Cruz T.
        • Reiner J.E.
        • Seashols-Williams S.J.
        Optical tweezers as an effective tool for spermatozoa isolation from mixed forensic samples.
        PLoS ONE. 2019; 14e0211810https://doi.org/10.1371/journal.pone.0211810
        • Williamson V.R.
        • Laris T.M.
        • Romano R.
        • Marciano M.A.
        Enhanced DNA mixture deconvolution of sexual offense samples using the DEPArray™ system.
        Forensic Sci. Int.: Genet. 2018; 34: 265-276https://doi.org/10.1016/j.fsigen.2018.03.001
        • Roper M.G.
        • Easley C.J.
        • Landers J.P.
        Advances in polymerase chain reaction on microfluidic chips.
        Anal. Chem. 2005; 77: 3887-3894https://doi.org/10.1021/ac050756m
        • Zhang C.
        • Xu J.
        • Ma W.
        • Zheng W.
        PCR microfluidic devices for DNA amplification.
        Biotechnol. Adv. 2006; 24: 243-284https://doi.org/10.1016/j.biotechadv.2005.10.002
        • Zhang Y.
        • Ozdemir P.
        Microfluidic DNA amplification—a review.
        Anal. Chim. Acta. 2009; 638: 115-125https://doi.org/10.1016/j.aca.2009.02.038
        • Chang C.-M.
        • Chang W.-H.
        • Wang C.-H.
        • Wang J.-H.
        • Mai J.D.
        • Lee G.-B.
        Nucleic acid amplification using microfluidic systems.
        Lab Chip. 2013; 13: 1225https://doi.org/10.1039/c3lc41097h
        • Gorgannezhad L.
        • Stratton H.
        • Nguyen N.-T.
        Microfluidic-based nucleic acid amplification systems in microbiology.
        Micromachines. 2019; 10: 408https://doi.org/10.3390/mi10060408
        • Ahrberg C.D.
        • Manz A.
        • Chung B.G.
        Polymerase chain reaction in microfluidic devices.
        Lab Chip. 2016; 16: 3866-3884https://doi.org/10.1039/C6LC00984K
        • Kulkarni M.B.
        • Goel S.
        Advances in continuous-flow based microfluidic PCR devices—a review.
        Eng. Res. Express. 2020; 2042001https://doi.org/10.1088/2631-8695/abd287
        • Yin J.
        • Suo Y.
        • Zou Z.
        • Sun J.
        • Zhang S.
        • Wang B.
        • Xu Y.
        • Darland D.
        • Zhao J.X.
        • Mu Y.
        Integrated microfluidic systems with sample preparation and nucleic acid amplification.
        Lab Chip. 2019; 19: 2769-2785https://doi.org/10.1039/C9LC00389D
        • Wittwer C.T.
        • Garling D.J.
        Rapid cycle DNA amplification: time and temperature optimization.
        Biotechniques. 1991; 10: 76-83
        • Farrar J.S.
        • Wittwer C.T.
        Extreme PCR: efficient and specific DNA amplification in 15–60 seconds.
        Clin. Chem. 2015; 61: 145-153https://doi.org/10.1373/clinchem.2014.228304
        • Giordano B.C.
        • Ferrance J.
        • Swedberg S.
        • Hühmer A.F.R.
        • Landers J.P.
        Polymerase chain reaction in polymeric microchips: DNA amplification in less than 240 seconds.
        Anal. Biochem. 2001; 291: 124-132https://doi.org/10.1006/abio.2000.4974
        • Nouwairi R.L.
        • Cunha L.L.
        • Turiello R.
        • Scott O.
        • Hickey J.
        • Thomson S.
        • Knowles S.
        • Chapman J.D.
        • Landers J.P.
        Ultra-rapid real-time microfluidic RT-PCR instrument for nucleic acid analysis.
        Lab Chip. 2022; (10.1039.D2LC00495J)https://doi.org/10.1039/D2LC00495J
        • Romsos E.L.
        • Vallone P.M.
        Rapid PCR of STR markers: applications to human identification.
        Forensic Sci. Int.: Genet. 2015; 18: 90-99https://doi.org/10.1016/j.fsigen.2015.04.008
        • Miralles V.
        • Huerre A.
        • Malloggi F.
        • Jullien M.-C.
        A review of heating and temperature control in microfluidic systems: techniques and applications.
        Diagnostics. 2013; 3: 33-67https://doi.org/10.3390/diagnostics3010033
        • Tan E.
        • Turingan R.S.
        • Hogan C.
        • Vasantgadkar S.
        • Palombo L.
        • Schumm J.W.
        • Selden R.F.
        Fully integrated, fully automated generation of short tandem repeat profiles.
        Invest. Genet. 2013; 4: 16https://doi.org/10.1186/2041-2223-4-16
        • Nouwairi R.L.
        • O’Connell K.C.
        • Gunnoe L.M.
        • Landers J.P.
        Microchip electrophoresis for fluorescence-based measurement of polynucleic acids: recent developments.
        Anal. Chem. 2021; 93: 367-387https://doi.org/10.1021/acs.analchem.0c04596
        • Paegel B.M.
        • Emrich C.A.
        • Wedemayer G.J.
        • Scherer J.R.
        • Mathies R.A.
        High throughput DNA sequencing with a microfabricated 96-lane capillary array electrophoresis bioprocessor.
        Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 574-579https://doi.org/10.1073/pnas.012608699
        • Horsman K.M.
        • Bienvenue J.M.
        • Blasier K.R.
        • Landers J.P.
        Forensic DNA analysis on microfluidic devices: a review.
        J. Forensic Sci. 2007; 52: 784-799https://doi.org/10.1111/j.1556-4029.2007.00468.x
        • Hopwood A.J.
        • Hurth C.
        • Yang J.
        • Cai Z.
        • Moran N.
        • Lee-Edghill J.G.
        • Nordquist A.
        • Lenigk R.
        • Estes M.D.
        • Haley J.P.
        • McAlister C.R.
        • Chen X.
        • Brooks C.
        • Smith S.
        • Elliott K.
        • Koumi P.
        • Zenhausern F.
        • Tully G.
        Integrated microfluidic system for rapid forensic DNA analysis: sample collection to DNA profile.
        Anal. Chem. 2010; 82: 6991-6999https://doi.org/10.1021/ac101355r
        • Le Roux D.
        • Root B.E.
        • Hickey J.A.
        • Scott O.N.
        • Tsuei A.
        • Li J.
        • Saul D.J.
        • Chassagne L.
        • Landers J.P.
        • de Mazancourt P.
        An integrated sample-in-answer-out microfluidic chip for rapid human identification by STR analysis.
        Lab Chip. 2014; 14: 4415-4425https://doi.org/10.1039/C4LC00685B
        • Smith C.
        • Strauss S.
        • DeFrancesco L.
        DNA goes to court.
        Nat. Biotechnol. 2012; 30: 1047-1053https://doi.org/10.1038/nbt.2408
        • Le Roux D.
        • Root B.E.
        • Reedy C.R.
        • Hickey J.A.
        • Scott O.N.
        • Bienvenue J.M.
        • Landers J.P.
        • Chassagne L.
        • de Mazancourt P.
        DNA analysis using an integrated microchip for multiplex PCR amplification and electrophoresis for reference samples.
        Anal. Chem. 2014; 86: 8192-8199https://doi.org/10.1021/ac501666b
        • Easley C.J.
        • Karlinsey J.M.
        • Bienvenue J.M.
        • Legendre L.A.
        • Roper M.G.
        • Feldman S.H.
        • Hughes M.A.
        • Hewlett E.L.
        • Merkel T.J.
        • Ferrance J.P.
        • Landers J.P.
        A fully integrated microfluidic genetic analysis system with sample-in–answer-out capability.
        Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 19272-19277https://doi.org/10.1073/pnas.0604663103
        • Ball G.
        • Dawnay N.
        • Stafford-Allen B.
        • Panasiuk M.
        • Rendell P.
        • Blackman S.
        • Duxbury N.
        • Wells S.
        Concordance study between the ParaDNA ® Intelligence Test, a Rapid DNA profiling assay, and a conventional STR typing kit (AmpFlSTR ® SGM Plus ®.
        Forensic Sci. Int.: Genet. 2015; 16: 48-51https://doi.org/10.1016/j.fsigen.2014.12.006
        • Liu P.
        • Li X.
        • Greenspoon S.A.
        • Scherer J.R.
        • Mathies R.A.
        Integrated DNA purification, PCR, sample cleanup, and capillary electrophoresis microchip for forensic human identification.
        Lab Chip. 2011; 11: 1041https://doi.org/10.1039/c0lc00533a
        • Read T.D.
        • Turingan R.S.
        • Cook C.
        • Giese H.
        • Thomann U.H.
        • Hogan C.C.
        • Tan E.
        • Selden R.F.
        Rapid multi-locus sequence typing using microfluidic biochips.
        PLoS ONE. 2010; 5e10595https://doi.org/10.1371/journal.pone.0010595
        • Hennessy L.K.
        • Mehendale N.
        • Chear K.
        • Jovanovich S.
        • Williams S.
        • Park C.
        • Gangano S.
        Developmental validation of the GlobalFiler® express kit, a 24-marker STR assay, on the RapidHIT® System.
        Forensic Sci. Int.: Genet. 2014; 13: 247-258https://doi.org/10.1016/j.fsigen.2014.08.011
        • Wiley R.
        • Sage K.
        • LaRue B.
        • Budowle B.
        Internal validation of the RapidHIT ® ID system.
        Forensic Sci. Int.: Genet. 2017; 31: 180-188https://doi.org/10.1016/j.fsigen.2017.09.011
        • Romsos E.L.
        • French J.L.
        • Smith M.
        • Figarelli V.
        • Harran F.
        • Vandegrift G.
        • Moreno L.I.
        • Callaghan T.F.
        • Brocato J.
        • Vaidyanathan J.
        • Pedroso J.C.
        • Amy A.
        • Stoiloff S.
        • Morillo V.H.
        • Czetyrko K.
        • Johnson E.D.
        • Tagyos J.
        • Murray A.
        • Vallone P.M.
        Results of the 2018 rapid DNA maturity assessment.
        J. Forensic Sci. 2020; 65: 953-959https://doi.org/10.1111/1556-4029.14267
      7. Scientific Working Group on DNA Analysis Methods Position Statement on Rapid DNA Analysis, Scientific Working Group DNA Analysis Methods (SWGDAM), 2017. 〈https://docs.wixstatic.com/ugd/4344b0_f84df0465a2243218757fac1a1ccffea.pdf〉.

      8. ASCLD Position Statement, American Society of Crime Laboratory Directors (ASCLD), 2017. 〈https://www.ascld.org/wp-content/uploads/2017/11/ASCLD-Position-Statement-RAPID-DNA.pdf〉.

      9. NDAA Position Statement on Use of Rapid DNA Technology, National District Attorneys Association, 2018. 〈https://dps.alaska.gov/getmedia/fb933229–8e52–4cf8–8fe0-cb72d5e039e3/NDAA-Statement-on-Use-of-Rapid-DNA-Technology-2018.pdf〉.

      10. Khan R. Dhand C. Sanghi S.K. Shabi T.S. Mishra A.B.P. Advanced microfluidics based point-of-care diagnostics: a bridge between microfluidics and biomedical applications. First edition. CRC Press, Taylor & Francis Group, Boca Raton2022
        • Konry T.
        • Bale S.S.
        • Bhushan A.
        • Shen K.
        • Seker E.
        • Polyak B.
        • Yarmush M.
        Particles and microfluidics merged: perspectives of highly sensitive diagnostic detection.
        Microchim. Acta. 2012; 176: 251-269https://doi.org/10.1007/s00604-011-0705-1
        • Wittwer C.T.
        • Herrmann M.G.
        Rapid thermal cycling and PCR kinetics.
        in: PCR Applications. Elsevier, 1999: 211-229
        • Repko A.F.
        • Szostak R.
        Interdisciplinary Research: Process and Theory. Fourth edition.,. SAGE,, Los Angeles2021
        • Volpatti L.R.
        • Yetisen A.K.
        Commercialization of microfluidic devices.
        Trends Biotechnol. 2014; 32: 347-350https://doi.org/10.1016/j.tibtech.2014.04.010
        • Li Z.
        • Bai Y.
        • You M.
        • Hu J.
        • Yao C.
        • Cao L.
        • Xu F.
        Fully integrated microfluidic devices for qualitative, quantitative and digital nucleic acids testing at point of care.
        Biosens. Bioelectron. 2021; 177112952https://doi.org/10.1016/j.bios.2020.112952
        • Fredrickson C.K.
        • Fan Z.H.
        Macro-to-micro interfaces for microfluidic devices.
        Lab Chip. 2004; 4: 526https://doi.org/10.1039/b410720a
        • Mapes A.A.
        • Stoel R.D.
        • de Poot C.J.
        • Vergeer P.
        • Huyck M.
        Decision support for using mobile Rapid DNA analysis at the crime scene.
        Sci. Justice. 2019; 59: 29-45https://doi.org/10.1016/j.scijus.2018.05.003
        • Maguire C.
        • Houck M.M.
        • Williams R.
        • Speaker P.J.
        Efficiency and the cost-effective delivery of forensic science services: insourcing, outsourcing, and privatization.
        Forensic Sci. Policy Manag.: Int. J. 2012; 3: 62-69https://doi.org/10.1080/19409044.2012.734546
        • Ragazzo M.
        • Melchiorri S.
        • Manzo L.
        • Errichiello V.
        • Puleri G.
        • Nicastro F.
        • Giardina E.
        Comparative analysis of ANDE 6C rapid DNA analysis system and traditional methods.
        Genes. 2020; 11: 582https://doi.org/10.3390/genes11050582
      11. M. Dolan, ‘Rapid DNA’ promises breakthroughs in solving crimes. So why does it face a backlash?, Los Angeles Times. (2019). 〈https://www.latimes.com/california/story/2019–09-24/rapid-dna-forensics-crime-police〉.

        • van Asten A.C.
        On the added value of forensic science and grand innovation challenges for the forensic community.
        Sci. Justice. 2014; 54: 170-179https://doi.org/10.1016/j.scijus.2013.09.003
        • Brown S.
        • Willis S.
        Complexity in forensic science.
        Forensic Sci. Policy Manag.: Int. J. 2010; 1: 192-198https://doi.org/10.1080/19409041003698454
        • Addington L.A.
        Hot vs. cold cases: examining time to clearance for homicides using NIBRS data.
        Justice Res. Policy. 2007; 9: 87-112https://doi.org/10.3818/JRP.9.2.2007.87
        • Mapes A.A.
        • Kloosterman A.D.
        • de Poot C.J.
        • van Marion V.
        Objective data on DNA success rates can aid the selection process of crime samples for analysis by rapid mobile DNA technologies.
        Forensic Sci. Int. 2016; 264: 28-33https://doi.org/10.1016/j.forsciint.2016.03.020
        • Lewis C.A.
        • Layne T.R.
        • Seashols‐Williams S.J.
        Detection of microRNAs in DNA extractions for forensic biological source identification.
        J. Forensic Sci. 2019; 64: 1823-1830https://doi.org/10.1111/1556-4029.14070
        • Lynch C.
        • Fleming R.
        RNA based approaches for body fluid identification in forensic science.
        WIREs Forensic Sci. 2021; 3https://doi.org/10.1002/wfs2.1407
        • Sijen T.
        Molecular approaches for forensic cell type identification: on mRNA, miRNA, DNA methylation and microbial markers.
        Forensic Sci. Int.: Genet. 2015; 18: 21-32https://doi.org/10.1016/j.fsigen.2014.11.015
        • Juusola J.
        • Ballantyne J.
        mRNA Profiling for body fluid identification by multiplex quantitative RT-PCR.
        J. Forensic Sci. 2007; 0 (070917231752009-???)https://doi.org/10.1111/j.1556-4029.2007.00550.x
        • Ingold S.
        • Dørum G.
        • Hanson E.
        • Berti A.
        • Branicki W.
        • Brito P.
        • Elsmore P.
        • Gettings K.B.
        • Giangasparo F.
        • Gross T.E.
        • Hansen S.
        • Hanssen E.N.
        • Kampmann M.-L.
        • Kayser M.
        • Laurent F.-X.
        • Morling N.
        • Mosquera-Miguel A.
        • Parson W.
        • Phillips C.
        • Porto M.J.
        • Pośpiech E.
        • Roeder A.D.
        • Schneider P.M.
        • Schulze Johann K.
        • Steffen C.R.
        • Syndercombe-Court D.
        • Trautmann M.
        • van den Berge M.
        • van der Gaag K.J.
        • Vannier J.
        • Verdoliva V.
        • Vidaki A.
        • Xavier C.
        • Ballantyne J.
        • Haas C.
        Body fluid identification using a targeted mRNA massively parallel sequencing approach – results of a EUROFORGEN/EDNAP collaborative exercise.
        Forensic Sci. Int.: Genet. 2018; 34: 105-115https://doi.org/10.1016/j.fsigen.2018.01.002
      12. T.R. Layne, R.L. Nouwairi, R. Fleming, H. Blair, J.P. Landers, Rapid Microchip Electrophoretic Separation of Novel Tran-scriptomic Body Fluid Markers for Forensic Fluid Profiling, Micromachines. (n.d.).

        • García M.G.
        • Pérez-Cárceles M.D.
        • Osuna E.
        • Legaz I.
        Impact of the human microbiome in forensic sciences: a systematic review.
        Appl. Environ. Microbiol. 2020; 86 (e01451-20)https://doi.org/10.1128/AEM.01451-20
        • Clarke T.H.
        • Gomez A.
        • Singh H.
        • Nelson K.E.
        • Brinkac L.M.
        Integrating the microbiome as a resource in the forensics toolkit.
        Forensic Sci. Int.: Genet. 2017; 30: 141-147https://doi.org/10.1016/j.fsigen.2017.06.008
        • Zhang J.
        • Liu W.
        • Simayijiang H.
        • Hu P.
        • Yan J.
        Application of microbiome in forensics.
        Genom., Proteom. Bioinforma. 2022; (S1672022922000961)https://doi.org/10.1016/j.gpb.2022.07.007
        • Kayser M.
        Forensic DNA Phenotyping: predicting human appearance from crime scene material for investigative purposes.
        Forensic Sci. Int.: Genet. 2015; 18: 33-48https://doi.org/10.1016/j.fsigen.2015.02.003
        • Schneider P.M.
        • Prainsack B.
        • Kayser M.
        The use of forensic DNA phenotyping in predicting appearance and biogeographic ancestry.
        Dtsch. Aerzteblatt Online. 2019; https://doi.org/10.3238/arztebl.2019.0873
        • Vidaki A.
        • Kayser M.
        From forensic epigenetics to forensic epigenomics: broadening DNA investigative intelligence.
        Genome Biol. 2017; 18: 238https://doi.org/10.1186/s13059-017-1373-1