Paper-based microfluidic devices: On-site tools for crime scene investigation

https://doi.org/10.1016/j.trac.2021.116406Get rights and content

Highlights

  • A critical review on paper-based microfluidics devices developed for forensic science issues.

  • Several strategies for developing paper-based microfluidics devices for forensic applications have been proposed.

  • Paper-based microfluidics technology can be used as a fast, reliable, and cost-efficient tool in forensic sciences.

  • Current challenges and future trends in paper-based microfluidics for forensic issues are discussed.

Abstract

The use of paper-based microfluidics devices (μPADs) for designing rapid, easy, and on-site devices has undergone a dramatic increase in the last few years and the development of applications in the field of forensic science has had concomitant advances. The use of μPADs at the crime scene is finalized not only to obtain a rapid response but also to have crucial information on evidence collection.

Several authors have proposed μPADs as alternative approaches to existing tests. These devices are designed to be used on-site without, or minimal, power sources. Furthermore, the technology provides prompt-readouts using a small sample volume, preserving important evidence for instrumental analysis.

This review aims to provide a critical evaluation of developed μPADs. The document includes a brief overview on fabrication methods and on detection strategies, and it assesses advantages and limitations of applications related to forensic matters. A final section is devoted to future developments.

Introduction

The initial investigation of a crime scene is of utmost importance to police and forensic examiners for collecting relevant evidence and for verifying the actions of potential suspects [1]. Technological advancements have enabled the detection of substances with great accuracy and precision, providing results with high sensitivity and reliability. However, instrument-based approaches that can only be implemented in laboratories, are expensive, not user-friendly and require highly skilled personnel for the complex analytical procedure and the result interpretation. Consequently, these technological approaches needing well equipped laboratories, are impractical for application at the crime scene.

Instead, crime scene investigators are bound to use “presumptive tests” to detect substances of forensic interest, ranging from explosives to clandestine preparation of drugs or toxicants either in the environment or in body fluids. However, these tests show clear shortcomings terms of sensitivity and specificity, which limit greatly their usefulness for the investigative actions. An important body of literature has piled on this subject, as witnessed by several reviews, but these papers often have not a specific focus on forensics [2], including different approaches [1,3] and analytical techniques [6]. On the other hand, in some cases, the reports are focused only on selected applications [4,5]. On these grounds, the present work has been primarily intended as a detailed review on developments in paper-based microfluidic technology in the context of the forensic investigation, and particularly in rapid evidence testing to be carried out the crime scene.

The first example of a paper microfluidic tool was reported in 1949 by Müller et al. The authors proposed the use of paraffin-patterned paper microfluidic channels as a method to hinder lateral diffusion of bands in paper chromatography [7]. However, this pioneering work did not receive much attention until the early years of this century when other researchers understood the usefulness of forming microchannels in paper sheets for analytical purposes. A well-known report which has boosted in paper microfluidics appeared in 2007 by the Whitesides group [8]. Paper-based microfluidics devices (μPADs) were developed to provide diagnostic devices for use in developing countries or remote areas, but recently have attracted the attention of several researchers working in forensic sciences.

Paper-based technology aims to produce microanalysis in compartments by delimiting hydrophilic areas through the use of barriers made of hydrophobic compounds. Paper has an inherent ability to provide fluidic flow as a result of capillarity action without the need for pumps or external actuation. Also, paper is inert, low-cost, abundant, and biodegradable.

The ASSURED criteria, (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free and Deliverable to end-users), works as a benchmark for evaluating the reliability of the disease-based analytical tests [9], but similarly is necessary also in the initial examination of a crime scene. Since the first applications of paper-based microfluidics for forensic purposes [18,19], several devices have been proposed. To date, a wide range of drugs and cutting agents can be identified by μPADs [[12], [13], [14], [16], [17], [18], [19], [20]]. These devices are also used in forensic serology to distinguish blood, urine, and semen [21] as well as in thanatochemistry to estimate time since death [22,23]. μPADs may also be used to detect warfare agents, such as pre-blast and post-blast explosives and nerve agents [11,[24], [25], [26], [27], [28]]. More recently, Azuaje-Hualde et al. have developed a proof-of-concept device for identifying the sex of a person from a biological sample [29].

In this paper we review reports on the use of paper-based devices for forensic aims, organizing the information into two sections. The first section is a short overview of the processes utilized in the fabrication of μPADs and the main detection methods, highlighting the advantages and limitations in the forensic context. The second section presents a critical view of devices intended for applications in the field, discussing both the advantages and disadvantages of these devices and describing their approaches towards measurements that can be performed directly at the crime scene.

Section snippets

Devices

Lateral flow assays (LFA) are the progenitors of paper-based devices, and are commercially available for detecting a wide range of pathogens and biomarkers. These devices are also used in many fields, including medicine, environmental monitoring and law enforcement [30]. The support in LFA devices is usually made of nitrocellulose, with portions modified with reagents selective for the analytes contained in the sample. LFA devices typically use labelled antibodies to capture and detect

Applications

Numerous authors have proposed the use of paper-based microfluidic devices as a novel technology available for application at the crime scene. These devices may also be used for screening samples, once they have been delivered to the laboratory. Specifically, devices have been developed for detecting body fluids and DNA, illicit drugs in seized materials and toxicological samples, explosives, gunshot residues, and chemical warfare. These applications summarized in Table 2, are critically

Challenges and future directions

Considering the high interest in achieving information of forensic interest already at the crime scene, in the recent times, the development of fieldable forensic devices has spread internationally [81,82]. The ideal device should provide sensitive and selective results in a range of time compatible with the crime scene investigation. Paper-based devices represent an innovative and promising tool with many possibilities of application for different forensic purposes, which may take advantage of

Conclusions

This report provides a critical review of fabrication methods of paper devices and of selected applications at the crime scene.

The first section describes the procedures used in developing paper microfluidic tools, highlighting pros and cons of the different fabrication approaches and detection methods. The analytical principles and the fabrication of each manufacturing technique are discussed.

The second section of the review discusses several applications so far developed to the main forensic

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bruce McCord has patent #US10036738B2 issued to Current assignee: Florida International University FIU. Bruce McCord has patent #US9791434B2 issued to Current assignee: Florida International University FIU.

Acknowledgments

The authors would like to acknowledge Margery S. Phipps for technical editing. A.Y. is supported by a PhD fellowship awarded by Fondazione Cariverona [grant number CUP B36J16002570003]. This work was in part supported by the Ministry of Science and Higher Education of the Russian Federation (funding number 075-15-2020-926 “Digital biodesign and personalized healthcare”).

References (99)

  • T. Tian et al.

    Integration of target responsive hydrogel with cascaded enzymatic reactions and microfluidic paper-based analytic devices (μPADs) for point-of-care testing (POCT)

    Biosens. Bioelectron.

    (2016)
  • L. McNeill et al.

    Origami chips: development and validation of a paper-based Lab-on-a-Chip device for the rapid and cost-effective detection of 4-methylmethcathinone (mephedrone) and its metabolite, 4-methylephedrine in urine

    Forensic Chem

    (2021)
  • T. Songjaroen et al.

    Novel, simple and low-cost alternative method for fabrication of paper-based microfluidics by wax dipping

    Talanta

    (2011)
  • W. Dungchai et al.

    Use of multiple colorimetric indicators for paper-based microfluidic devices

    Anal. Chim. Acta

    (2010)
  • T.M.G. Cardoso et al.

    Versatile fabrication of paper-based microfluidic devices with high chemical resistance using scholar glue and magnetic masks

    Anal. Chim. Acta

    (2017)
  • R.A.G. de Oliveira et al.

    A simple method to produce 2D and 3D microfluidic paper-based analytical devices for clinical analysis

    Anal. Chim. Acta

    (2017)
  • M.A. Ostad et al.

    A novel direct and cost effective method for fabricating paper-based microfluidic device by commercial eye pencil and its application for determining simultaneous calcium and magnesium

    Microchem. J.

    (2017)
  • L.R. Sousa et al.

    Instrument-free fabrication of microfluidic paper-based analytical devices through 3D pen drawing

    Sensor. Actuator. B Chem.

    (2020)
  • D.M. Cate et al.

    Recent developments in paper-based microfluidic devices

    Anal. Chem.

    (2015)
  • L. Pereira De Oliveira et al.

    Forensics in hand: new trends in forensic devices (2013-2017)

    Anal. Methods.

    (2018)
  • K. Evans-Nguyen et al.

    Fieldable mass spectrometry for forensic science, homeland security, and defense applications

    Mass Spectrom. Rev.

    (2020)
  • R.H. Müller et al.

    Automatic paper chromatography

    Anal. Chem.

    (1949)
  • A.W. Martinez et al.

    Patterned paper as a platform for inexpensive, low-volume, portable bioassays

    Angew Chem. Int. Ed. Engl.

    (2007)
  • K. Land

    Paper-based Diagnostics

    (2019)
  • J. Lu et al.

    Electrochemical DNA sensor based on three-dimensional folding paper device for specific and sensitive point-of-care testing

    Electrochim. Acta

    (2012)
  • D. Pardasani et al.

    μ-PADs for detection of chemical warfare agents

    Analyst

    (2012)
  • G. Musile et al.

    The development of paper microfluidic devices for presumptive drug detection

    Anal. Methods.

    (2015)
  • T.E. Lockwood et al.

    idPAD: paper analytical device for presumptive identification of illicit drugs

    J. Forensic Sci.

    (2020)
  • L. Wang et al.

    An aptamer-based paper microfluidic device for the colorimetric determination of cocaine

    Electrophoresis

    (2018)
  • J. Narang et al.

    Hydrothermally synthesized zinc oxide nanorods incorporated on lab-on-paper device for electrochemical detection of recreational drug, Artif. Cells

    Nanomedicine Biotechnol

    (2018)
  • N. Ansari et al.

    Determination of Cause of Death Using Paper-Based Microfluidic Device as a Colorimetric Probe †

    (2017)
  • L.F. Mendes et al.

    Forensic electrochemistry: electrochemical study and quantification of xylazine in pharmaceutical and urine samples

    Electrochim. Acta

    (2019)
  • C.A. Chen et al.

    Fast analysis of ketamine using a colorimetric immunosorbent assay on a paper-based analytical device

    Sensor. Actuator. B Chem.

    (2019)
  • A.A. Dias et al.

    Detection of analgesics and sedation drugs in whiskey using electrochemical paper-based analytical devices

    Electroanalysis

    (2018)
  • R.L. Cromartie et al.

    Development of a microfluidic device (μPADs) for forensic serological analysis

    Anal. Methods.

    (2019)
  • A. Pesenti et al.

    Coupling paper-based microfluidics and lab on a chip technologies for confirmatory analysis of trinitro aromatic explosives

    Anal. Chem.

    (2014)
  • M.O. Salles et al.

    Explosive colorimetric discrimination using a smartphone, paper device and chemometrical approach

    Anal. Methods.

    (2014)
  • K.L. Peters et al.

    Simultaneous colorimetric detection of improvised explosive compounds using microfluidic paper-based analytical devices (μPADs)

    Anal. Methods.

    (2015)
  • S. Cinti et al.

    Fully integrated ready-to-use paper-based electrochemical biosensor to detect nerve agents

    Biosens. Bioelectron.

    (2017)
  • E. Azuaje-Hualde et al.

    Naked eye Y amelogenin gene fragment detection using DNAzymes on a paper-based device

    Anal. Chim. Acta

    (2020)
  • C. Carrell et al.

    Beyond the lateral flow assay: a review of paper-based microfluidics

    Microelectron. Eng.

    (2019)
  • Y. Yang et al.

    Paper-based microfluidic devices: emerging themes and applications

    Anal. Chem.

    (2017)
  • P.N. Nge et al.

    Advances in microfluidic materials, functions, integration, and applications

    Chem. Rev.

    (2013)
  • G.G. Morbioli et al.

    Technical aspects and challenges of colorimetric detection with microfluidic paper-based analytical devices (μPADs) - a review

    Anal. Chim. Acta

    (2017)
  • X. Jiang et al.

    Fabrication and Operation of Paper-Based Analytical Devices

    (2016)
  • J. Olkkonen et al.

    Flexographically printed fluidic structures in paper

    Anal. Chem.

    (2010)
  • N. Bhattacharjee et al.

    The upcoming 3D-printing revolution in microfluidics

    Lab Chip

    (2016)
  • Y. He et al.

    3D printed paper-based microfluidic analytical devices

    Micromachines

    (2016)
  • R. Lu et al.

    Rapid prototyping of paper-based microfluidics with wax for low-cost, portable bioassay

    Electrophoresis

    (2009)
  • Cited by (22)

    • Microfluidic paper-based analytical devices for cancer diagnosis

      2023, Sensors and Actuators B: Chemical
      Citation Excerpt :

      This review paper summarizes the current status of PADs for cancer diagnosis. It adds to the literature that includes reviews taking a general perspective [57–59]; or reviews focusing on: functionalization of the paper substrate [60]; different PAD configurations and design (LFAs, 2D and 3D µPADs) [61]; sensing techniques such as colorimetry [12] or electrochemical [62] detection; and specific applications such as detection of bacteria and viruses [51], detection of food contaminants [63], food safety and quality analysis [64], personalized health care [65], and crime scene investigation [66]. This review discusses the different PADs used for cancer biomarker detection in detail through discussing the different paper substrates used and their surface modifications, the different configurations of PADs and their fabrication methods, assay principles, recognition elements and modifications, sensing techniques, and improvement methods for the produced signal.

    • A paper chromatographic-based electrochemical analytical device for the separation and simultaneous detection of carbofuran and carbaryl pesticides

      2023, Sensors and Actuators B: Chemical
      Citation Excerpt :

      The devices are fabricated by creating hydrophobic barriers on the paper sheet and defining the hydrophilic microchannels and test zones. Paper-based microfluidics presents many advantages, such as portability, low sample, and reagent consumption, and can perform multi-analyte detection [21,27–29]. In recent decades, paper-based microfluidics devices have been applied to the detection of target analytes in several applications, such as clinical diagnostics [30–32], environmental pollutants [33], and pharmaceuticals [34].

    View all citing articles on Scopus
    View full text