Opinion Point-of-Care Detection Devices 

for Food Safety Monitoring: Proactive 

Disease Prevention 
Marie Yung-Chen Wu,1 Min-Yen Hsu,2,3 Shih-Jen Chen,4 De-Kuang Hwang,4 
Tzung-Hai Yen,5,6,7,* and Chao-Min Cheng8,* 
Food  safety  has  become  an  increasingly  significant  public  concern  in  both  developed  and  under-developed nations 
around  the world; it increases morbidity, mortality, human suffering, and economic burden. This Opinion focuses on 
(i)  examining  the  influence  of  pathogens  and  chemicals  (e.g.,  food  additives  and  pesticide  residue)  on  food-borne 
illnesses,  (ii)  summarizing  food  hazards  that  are  present  in  Asia,  and  (iii)  summarizing  the  array  of  current  point- 
of-care  (POC)  detection  devices  that  have  potential  applications  in  food  safety  monitoring.  In addition, we provide 
insight  into  global  healthcare  issues  in  both  developing  and  under-developed  nations  with  a  focus  on  bridging  the 
gap  between  food  safety  issues  in  the  public  sector  (associated  with  relevant  clinical  cases)  and  the  use  of  POC 
detection devices for food safety monitoring. 
POC Food Safety Assessment Food-borne illnesses (see Glossary) impart a startling public morbidity rate, with outbreaks of 
food-related health hazards occurring at an unpredictable and varying extent in both develop- ing and developed nations [1] 
(http://apps.who.int/iris/bitstream/10665/199350/1/ 9789241565165_eng.pdf). Therefore, proper handling and preparation of 
food is crucial to ensure quality and preserve societal health during food production, manufacturing, packaging, and 
transportation (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm494125.htm). 
Food  safety  issues  become  further  magnified  when  food  is  manufactured  and  transported  to  and  from  different  regions locally, 
regionally,  and  worldwide.  Food  contamination  from  patho-  gens  (i.e.,  bacteria  and  viruses)  and  chemicals  such  as  pesticide 
residues,  metals,  and  other  adulterants  are  responsible  for  severe  morbidity,  mortality,  and  wide-reaching  economic burden [1]. 
The  impact  of  these  food  hazards  on  human  health  may  range  from  the  immediate  to the long-term, causing temporary disease, 
acute  organ  damage,  or  cancer.  Enhanced  monitoring  of  food  safety  should  be  more  frequent  and  larger  in  scale,  performed  at 
multiple  locations,  and  implemented  across  the  points  of  production  both  through  the  various  levels  of  distribution  and  at  the 
consumer  endpoint  [2].  Crucial  control  points,  in  other  words  specific  points,  procedures,  or  steps  in  food  manufacturing  and 
delivery,  are  used  as  examination  checkpoints  in  food  safety  standard  operating procedures. Unfortunately, the current practices 
of food safety monitoring are not ideal in all circumstances largely because of the high cost of 
Trends 
Unhealthy  food  additives  and  pesticide  residues  from  preparation,  handling,  and  storage  are  increasingly discov- ered in and on 
market-ready food pro- ducts. In the USA, food-borne illnesses account for 325 000 hospitalizations and 5000 deaths annually. 
POC  detection  devices  employ  tech-  nology that can be used to detect unhealthy food adulterants without centralized, expensive, 
laboratory- centric equipment. 
1 
Department of Medicine, National Taiwan University, Taipei 100, Taiwan 2Department of Ophthalmology, Taichung Veterans 
General Hospital, Taichung 407, Taiwan 3School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan 
4Department of Ophthalmology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan 5Poison Center, 
Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Linkou 333, Taiwan 6Kidney Research 
Center, Chang Gung Memorial Hospital, Linkou 333, Taiwan 7Center for Tissue Engineering, Chang Gung Memorial Hospital, 
Linkou 333, Taiwan 8Institute of Biomedical Engineering, 
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rights reserved. 
 
National routine laboratory examination. Time-consuming operations based in central laboratories that require specialized, 
trained personnel hinder the possibility of more frequent and regular 
Tsing Hua University, Hsinchu 300, Taiwan *Correspondence: point-of-care(POC) testing [3], which is especially advantageous 
in remote or low-resource 
m19570@adm.cgmh.org.tw 
settings. 
(T.-H. Yen) and chaomin@mx.nthu.edu.tw (C.-M. Cheng). In this article we summarize specific public food safety issues – 
particularly those in Asia – paired with clinically relevant impacts, and discuss current research efforts and diagnostic tools to 
propose potential solutions for remediation. Multiple instances of insufficient food safety monitoring have resulted in a 
significant number of illnesses and even death [1,4] (http://origin. 
glb.cdc.gov/mmwr/preview/mmwrhtml/mm6315a3.htm?s_cid=mm6315a3_w). Research in the use of POC detection devices has 
produced significant advances. In particular, new types of diagnostic tools have been found to be inexpensive, robust, easy to use, 
and highly scalable for mass production. Such tools include microfluidic-based detection and paper-based ana- lytical devices [5]. 
Advances in POC testing in recent years have generated single-platform devices capable of multiple, simultaneous target testing 
[6–10]. Further, integrating recent technologies, such as paper-based analytical devices, with smartphone cameras can speed up 
results recording and analysis. These advances allow local public healthcare workers to screen for potential issues associated with 
food safety and allow remote medical practitioners to make rapid POC decisions. This progress has increased the potential for 
providing POC testing and medical services to remote areas, and offers more comprehensive integration of testing results for 
monitoring food safety [11–13]. 
Global Public Food Safety Issues Consumers in Asia have suffered from a series of food safety incidents over the past ten years 
(Table 1). The 2008 melamine milk calamity remains one of the largest scandals in the history of China [14]. This incident 
involved the adulteration of milk and infant formula, as well as other food materials and components, with melamine, resulting in 
an estimated 300 000 total health victims. Six infants died from kidney stones and other kidney damage, and an estimated 54 000 
babies were hospitalized as a result of this event. The addition of melamine to milk gave the false appearance of higher protein 
content, leading to protein deficiency and contamination of baby formula [14]. An additional incident took place in May of 2011 
regarding the illegal use of the phthalate plasticizer di(2-ethylhexyl) phthalate (DEHP) as a clouding agent in foods and 
beverages produced in Taiwan [15]. Clouding agents are legal food additives, primarily made of gum Arabic, emulsifying agents, 
palm oil, or other food additives. DEHP, however, is categorized as an industrial plasticizer which should not be added to food. 
Upon investigation, it was found that the illegal clouding agents containing DEHP had appeared on the market as early as two 
decades before, and were used because the resulting clouding agent was white in color and esthetically pleasing [15]. A third 
example occurred in August of 2012 (www. japantimes.co.jp/news/2012/08/20/national/e-coli-outbreak-in-hokkaido-kills-seven- 
sickens-over-100-others/#.WCyJ1JN96o8) and involved a major food-poisoning outbreak in Hokkaido that killed seven Japanese 
people, including a 4-year-old child, and sickened more than 100 others who had eaten pickled cabbage tainted with E. coli 
bacteria. It is clear that poor food safety practices were employed in these instances, and we posit that POC testing has the 
potential to remedy such shortcomings in food handling, preparation, and storage by providing a ready tool for analysis. 
POC Detection Devices and Food Safety Monitoring POC detection devices can be used in a variety of instances, including each 
of the following: (i) environmental monitoring of infectious agents, metals, or other adulterants; (ii) self-applied quality control 
by companies within the manufacturing chain of food production; (iii) routine safety inspection by governmental agencies; (iv) 
toxin screening and cluster identification in emergency and urgent care clinical settings; (v) public health and policy support for 
building a 
Trends in Biotechnology, April 2017, Vol. 35, No. 4 
289 
 
Table 1. Selected Food Safety Incidents in Asia over the Past 10 Years. 
Date Geographic 
area 
Adulterant/event Remark Refs 
September 2008 
China Melamine Illegal use of melamine to increase the 
nitrogen content of milk and its apparent protein content. 
[14] 
May 2011 Taiwan DEHPa Illegal use of DEHP in clouding agents 
for use in foods and beverages. 
[15] 
November 2011 
India Methanol A methanol-contaminated batch of 
illegal alcohol killed 143 people in India in November 2011. Victims around the Sangrampur District became sick after drinking 
a home-brewed alcoholic beverage known as chepti. The drinks contained methanol, a highly toxic chemical that, when ingested, 
can lead to blindness or death. 
[61] 
August 2012 Japan E. coli An outbreak of E. coli killed seven and 
infected more than 100 people. 
www.japantimes.co.jp/ news/2012/08/20/ national/e-coli- outbreak-in-hokkaido- kills-seven-sickens- over-100-others/ 
#.WDHI6Feg2CR 
March 2013 Taiwan Maleic 
anhydride 
Illegal use of maleic anhydride in modified starch for use in foods. Began in Taiwan in March of 2013 as investigators discovered 
that chemical suppliers from south Taiwan had sold maleic acid, a well-known nephrotoxin, to the food industry. Maleic acid is 
not an approved food additive, but adding maleic acid to starch can increase the flexibility and viscosity of food, making it more 
palatable. The affected products included flat rice noodles, round meat dumplings, oden, tapioca balls, tofu puddings, rice cake, 
taro, and sweet potato dumplings. 
www.roc-taiwan.org/ uslax_en/post/2209. html 
August 2013 Taiwan Top Pot Bakery 
scandal 
Untrue claim that breads were made with natural ingredients and zero flavoring additives. The upper limit of intake could be 
easily exceeded after daily consumption of only 40 g of tapioca balls or 70 g of oden by a 60 kg man. In August 2013, a famous 
bakery chain in Taiwan that had boasted in its advertisements that its breads were made with natural ingredients and zero 
artificial flavoring, was found to have been adding artificial flavoring to its breads. According to EU Scientific Committee on 
Food (SCF) regulations, the tolerable daily intake (TDI) value for maleic anhydride is set at 0.5 mg/kg per person. The reported 
concentrations of maleic acid in tapioca balls and oden were 779 mg/kg and 496 mg/kg, respectively. 
www.chinapost.com. tw/editorial/ taiwan-issues/2013/08/ 28/387442/p2/ Bakery-scandal.htm 
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Glossary. 
Food-borne illness: any illness resulting from food-associated spoilage, pathogens, chemical toxins, or natural toxins. Food 
safety: a scientific discipline that describes food handling, preparation, and storage methods designed to prevent food-borne 
illness. These include food labeling, food hygiene, and inspections for unhealthy food additives and pesticide residue. 
Microfluidic paper-based analytical devices (mPADs): analytical, paper-based devices that can be designed in 2D or 3D patterns 
that leverage their intrinsic capillary capacity for wicking microliter-scaled fluids along hydrophilic channels without the need for 
external application of electricity. Point of care (POC): patient care in the emergency room, in primary clinics, at home, or in 
other non- hospital settings where diagnoses can be made and treatment regimens can be considered. 
 
Table 1. (continued) 
Date Geographic 
area 
Adulterant/event Remark Refs 
October 2013 
https://en.wikipedia. org/wiki/2013_ Taiwan_food_scandal 
January 2014 
Taiwan Copper 
Illegal use of copper chlorophyllin in chlorophyllin 
olive oil. In October 2013, a Taiwanese foodstuff company was found to have used copper chlorophyllin, an illegal coloring 
agent for cooking oil, in its olive oil, and to have adulterated its higher- end cooking oil with cheaper cottonseed oil. 
Japan Malathion In January 2014, the Japanese 
www.rt.com/news/ government discovered a serious 
japan-poisoning- outbreak of food poisoning after over 
food-pesticides-331/ 1000 people across the country fell sick from food contaminated with 
malathion pesticide. Many consumers complained about having gastrointestinal symptoms after eating packaged frozen 
croquettes, frozen chicken teriyaki with mayonnaise, or pizza. 
July 2014 China Meat incident In July 2014, a reporter in Shanghai 
captured footage of contaminated meat being processed inside a factory. Upon investigation, the government found that expired 
meat products were being repackaged and processed with new expiration dates, and approximately 3000 cases of contaminated 
beef had already been sold. The company had been supplying their meat products to many big fast- food chains in China. 
www.forbes.com/sites/ greatspeculations/ 2014/09/11/ mcdonalds-faces- declining-sales- in-asia-after- china-food-scandal/ 
#94f117561ebe 
September 2014 
www.nytimes.com/ 2014/09/19/opinion/ taiwans-gutter-oil- scandal.html?_r=0 
December 2014 
Taiwan Gutter oil 
In Taiwan in September 2014, incident 
authorities struggled to control a food scare caused by 645 tons of adulterated gutter oil produced by a company and distributed 
to more than 1200 restaurants, schools, and food processors. The company had been buying ‘gutter oil,' in other words recycled 
oil from restaurant waste and animal byproducts, from an illegal factory and mixing it with lard oil to produce its cooking oil. 
Taiwan Dimethyl yellow In December 2014, Taiwan authorities 
www.ibtimes.com/ ordered countrywide recall of dried 
taiwan-tofu-recall- bean curd after an inspection in Hong 
cancer-scare-marks- Kong discovered that it contained 
latest-taiwanese- traces of a banned industrial dye, 
food-scandal-1761260 dimethyl yellow. According to the 
http://www.inchem. International Agency for Research on 
org/documents/iarc/ Cancer, dimethyl yellow is classified as 
 vol08/p- a possible carcinogen to humans 
dimethylaminobenzene. (group 2B). Dimethyl yellow is 
html carcinogenic and known to produce liver tumors in rats following contact by several 
routes, and to produce bladder tumors in dogs when ingested. 
Trends in Biotechnology, April 2017, Vol. 35, No. 4 
291 
 
Table 1. (continued) 
Date Geographic 
area 
Adulterant/event Remark Refs 
April 2015 Taiwan Industrial grade 
magnesium carbonate 
www.pharmacychoice. com/News/article.cfm? Article_ID=1353194 
April 2015 Taiwan Pesticide 
residues 
In April 2015, police carried out raids in several areas of central Taiwan to assess the penetration of spices and foodstuffs 
produced using industrial grade magnesium carbonate. They discovered that several dozen food products, including flavored rice 
powder, number 6 and number 7, edible red food coloring, and ground pepper, had still not been removed from shelves. 
Moreover, the chemicals had also made their way into several health and medical products. 
In April 2015, Taiwan authorities 
www.chinapost.com. revealed that imported rose tea from a 
tw/taiwan/national/ soft drink chain contained 13 types of 
national-news/2015/ pesticide residues, including four types 
04/15/433659/ of dichlorodiphenyltrichloroethane: 
Local-rose.htm dichlorodiphenyldichloroethylene, carbendazim, dimethoate, and 
cypermethrin. After this discovery, the government launched a nationwide investigation into tea chains. As many tea store chains 
became embroiled in the pesticide residue scare, many food safety specialists urged the public to refrain from drinking tea made 
from a first infusion and demanded that the government step up its monitoring of pesticides in edible products. 
June 2015 India Instant noodles In India in June 2015, artificial additives such as monosodium glutamate were detected in Maggi 
instant noodles (Nestlé), although the company had consistently denied using such additives. After the authorities in India 
discovered high levels of lead in these noodles, the Indian government banned Maggi. Tests in six countries, including Canada, 
Singapore, the UK, and the USA, have determined the product to be safe for consumption, but Nestlé responded by destroying 
more than 35000 tons of products. 
http://thediplomat.com/ 2015/09/ india-and-food-safety/ 
November 2015 
Taiwan Industrial grade 
In November 2015, local authorities 
www.youtube.com/ sodium nitrate 
found that a Taipei-based hot-dog and 
watch?v=fBDwGQNIi7o and nitrite 
ham factory had used industrial grade sodium nitrate and nitrite in their products. The industrial grade additives were used to 
produce hot-dogs, ham, and bacon products that were distributed to many downstream stores. 
aAbbreviation: DEHP, di(2-ethylhexyl) phthalate. 
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food  surveillance  system  or  food  safety  map;  (vi)  individual health protection (e.g., testing for food-borne allergens) for end-use 
consumers;  and  (vii)  improved  monitoring  in  remote  rural  areas  [16–20].  Figure  1  shows  how  rapid  POC  diagnosis  could  be 
incorporated  into  method-  ology  for  enforcing  food  safety  issues  from  a  variety of perspectives. We draw particular attention to 
the  suitability  of  POC  platforms  for  remote  rural  areas  and  the  fact  that  results  can  be  captured using a smartphone camera and 
easily uploaded to a cloud computing system via the internet. 
Early  POC  detection  devices  focused  primarily  on  rapid  on-site  medical  diagnosis,  and  were  not  expanded  to  applications  in 
other  fields,  but they have since been developed for use in conjunction with DNA microarrays, chip-based PCR tests, peptide and 
oligonucleotide  librar-  ies,  drug  screening,  and  cell  culture  methods  [21–23].  The  immense  growth  in  POC  detection  device 
research  has  laid  the  groundwork  for  additional  implementation,  including  their use in ensuring food safety [18,23]. Research to 
date  has  led  to  the  refinement  of techniques that are tailor-made for the demands of food safety monitoring. The ability to handle 
micro-amounts  of  samples,  the  precise  manipulation  of  fluids,  the  capacity  for  highly  sensitive  detection,  and the production of 
easily  read  and  interpreted  diagnostic  outputs  all  underscore  the  clear  capabilities  for  implementing  broad  and  specific  food 
safety  protocols  with  POC  detection  devices  [24–26].  As  with  any  POC  detection  device,  the  judicious  selection  of  suitable 
substrate  materials  for  developing  application-specific  detection  platforms  is  highly  necessary.  Many  platforms  may  be 
well-suited  for  food  safety  monitoring,  but  we  will  examine  three  here:  (i)  paper-based  analytical  devices;  (ii)  hydrophilic 
substrate-based  detection  devices,  using  bamboo  or  cotton  as  materi-  als;  and  (iii)  microfluidic-based detection devices. We are 
keenly  optimistic  about  the  enormous potential for combining platforms, such as paper-based analytical devices and hydrophilic- 
based  detection  devices,  with  smartphone  technology  to  facilitate  rapid  recording  and  analysis  [27].  When  hybridized  with 
smartphone-based  technologies, POC detection devices are capable of superior algorithmic complexity and computational power, 
and  the  arrangement  offers  the  additional  benefits  of  being  both  wireless  and  portable [27,28]. We contend that leveraging such 
combinations could very well lead to a transformative revolution in the practice of food safety monitoring. 
POC  detection  devices  for  food  safety  monitoring  may  be  used  to  detect  many  hazards  including  (i) food-borne or water-borne 
bacteria, (ii) organophosphate-based pesticides, (iii) metals, and (iv) other chemicals. 
Food-Borne or Water-Borne Bacteria Detection Food-borne bacteria can produce gastrointestinal discomfort, diarrheal diseases, 
and even death. The World Health Organization recently reported that as many as 600 million children in regions including 
Central Africa and Southeast Asia fall ill each year after consuming contami- nated foods 
(http://apps.who.int/iris/bitstream/10665/199350/1/9789241565165_eng.pdf). In regions lacking institutionalized central 
laboratory equipment and trained operators to identify deleterious pathogens and chemicals, locals are unlikely to receive rapid 
diagnosis or appro- priate care. When analyzed on a large scale, food manufacturers and national economies alike are impacted 
negatively by food hazards (http://money.cnn.com/2016/03/15/investing/ chipotle-loss-e-coli/). Among food-borne bacteria, 
Escherichia, Listeria, Salmonella, Shigella, and Vibrio are five of the most common diarrhea-causing pathogens [1,29]. Rapid 
confirmation of these causative bacteria in food-borne disease outbreaks can certainly help to save more lives. However, the 
current methods for detecting food-borne bacterial pathogens still involve both culturing, a time-consuming process that requires 
as many as 5–7 days to acquire results, and PCR methodology, which relies intensively on laboratory personnel and instruments. 
Rapid POC detection devices could diagnose bacterial contaminants and provide similar levels of sensitivity to current methods 
in mere hours [30]. 
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293 
 
 Central laboratory 
Figure  1.  Incorporating  Rapid  Diagnostics  into  Enhanced  Food  Safety.  This  involves  interplay  among  (A)  prospects  on  global 
health  and  goals  for  human  development;  (B)  the  roles  of  governments  and  the  media  as  managers  and  watchdogs  of  political 
will;  (C)  the  breadth  and  array  of  testable  agents;  (D)  the  central  laboratory  through  which  redundant  verification  and  quality 
assurance  can  be  carried  out;  and,  finally,  (E)  the  various  settings  in  which they will be employed and the users operating them. 
(F) The leveraged technologies on which point-of-care (POC) detection devices are based. 
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Trends in Biotechnology, April 2017, Vol. 35, No. 4 
Prevent morbidi es Save lives Relieve economic burdens 
Food -borne bacteria Toxic metals Organophosphate- based pes cides Other chemicals 
Global public health prospects 
(B) 
(A) 
(F) 
(C) 
(E) Se ngs 
(D) and users 
Water W 
and d 
soil monitoring Food-produc on chain Rural areas Health inspec on Clinical se ngs for cluster iden fica on 
End-customer 
il 
i 
i 
Implementa on of regula ons Regular monitoring Surveillance system Food hazard repor ng 
Devices and t echnologies for POC detec on 
Laboratory instruments Specialized operators 
Government and media 
Agents 
 
Organophosphate-Based Pesticides When ingested, organophosphate-based pesticides act as neurotoxic agents in mammals, 
inactivating acetylcholinesterase (AChE) at synaptic junctions and causing neuronal, hepatic, and renal impairments [31]. 
Originating from agricultural runoff, they may reach food or water supplies, causing significant harm to humans and animals, 
particularly within rural agrarian communities. In contrast to conventional methods for the detection of pesticides, which rely on 
unwieldy liquid chromatography (LC) techniques for the differentiation of chemical components [32,33], POC detection devices 
provide rapid, sensitive, and portable analysis directly to those in the field [34,35]. 
Metals Metallic elements of high atomic weight can bioaccumulate. These metals enter metabolic systems via contaminated 
water and soil, potentially causing health damage even at low concentrations [36–38]. Exposure to particular toxic metals and 
trace elements can cause fetal impairment, acute/chronic organ injury, and eventual carcinogenesis. Arsenic, cadmium, lead, and 
mercury are all toxic metals that arouse public attention; highly sensitive testing to determine their presence in the environment is 
crucial [36–38]. Currently, commercialized testing kits to detect toxic metals do provide qualitative results [39], but POC 
detection devices outlined in recent research have demonstrated increasingly rapid, multiplexed, sensitive, and quantitative 
results [40]. 
Other Chemicals (Nitrite, Nitrate, Aminoglycoside Antibiotic Residues) In addition to the aforementioned categories, other 
chemicals that must be monitored to ensure food safety include nitrites and nitrates, which are potentially carcinogenic, as well as 
oto- and nephrotoxic aminoglycoside antibiotics [41,42], which may find themselves in the food supply of antibiotic-treated beef, 
poultry, fish, and dairy products. POC devices offer great potential for their detection as well [43]. 
Various Detection Approaches in Food Safety Monitoring In this section we have chosen to focus on the newer types of POC 
detection devices because microfluidic-based detection devices (i.e., using polydimethylsiloxane as the substrate material for 
making microfluidic devices) have been extensively documented in the literature [20,24,44,45]. 
Paper-Based Analytical Devices Paper, composed of cellulose, is a substrate material whose features and fabrication methods are 
the most established among POC detection devices. Paper-based analytical devices include dipstick assays, lateral flow assays 
(LFAs), and microfluidic paper-based analytical devices (mPADs). In the past decades, dipstick assays and LFAs have been 
extensively applied for urine and pregnancy tests, respectively. In this Opinion we strongly emphasize mPADs. Microfluidic 
paper-based analytical devices, also called ‘lab on paper’ devices, first demonstrated in 2007 by Martinez et al. [25], include flow 
paths that permit microliter-scale sample manipulation. Such devices can be designed in 2D or 3D patterns, leveraging intrinsic 
capillary capacity for wicking microliter-scale fluids along hydrophilic channels, and without the need for external application of 
electricity [46,47]. Paper, compared to other microfluidic device substrates such as glass, silicon, or plastic, demonstrates several 
advantages for use in food safety applications. Paper is desirable because it is affordable, lightweight, self-powering, 
biodegradable, and easily manufactured; all these characteristics make it convenient for in-field, domestic, or resource-poor usage 
(Figure 2) [18]. Several recent reviews have provided the general background and the specific applications of mPADs 
[17,19,48–50]. 
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295 
 
 Food safety detec on devices 
Figure 2. Some Advantageous Properties of Point-of-Care (POC) Devices for Food Safety Monitoring. Illustration in (A) adapted 
from [62]. 
Hydrophilic Substrate-Based Detection Devices There are other lignocellulose-based detection device materials beyond paper, 
for example thread, cotton, and bamboo, that show potential for use in food safety applications [18]. Lignocellulose-based 
detection devices are constructed using either a single lignocellulose or a hybrid design consisting of multiple types of 
lignocellulose [51]. Lignocellulose – composed of plant cell walls, whose major components are cellulose, hemicelluloses, and 
lignin, which together form microfibril structures –is found in abundance in otherwise resource-poor regions. Because such 
materials are disposable, eco-friendly, inexpensive, and lightweight, they are well-suited platforms for food safety monitoring 
devices. These matrix-based materials are readily manufactured and can use their wicking capacity to control fluid dimensions 
without any added energy or instrumentation, thus facilitating economical and practical real-world usage [52]. While paper-based 
analytical devices have become the de facto platform for low-cost detection, and have been discussed extensively in research and 
employed commercially, other lignocellulose-based detection materials such as cotton, cloth, wood, and bamboo remain under 
development. The use of bamboo is highly promising and readily available on the market in the form of stirrers, which Kuan et 
al. [51] have successfully used to make both single-material 
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Trends in Biotechnology, April 2017, Vol. 35, No. 4 
(B) 
User-friendliness and simple opera on to provide a clear workflow and decrease the costs of operator training 
(C) (A) 
Portability and durability Analy cal capacity to 
provide on-site data analysis, transfer, and storage through 
to facilitate transport through rugged and distant landscapes a wireless network 
(D) (F) 
Integra on of mul ple biomarkers of detec on without addi onal heavy 
Eco-friendliness, to eliminate non-disposable waste 
instrumenta on 
(E) 
Compact volume and weight to facilitate ease of transporta on 
 
(bamboo-only),  and  hybrid  (bamboo  and  wood)  lignocellulose-based  detection  devices  for  the  rapid  bioanalysis  of  food  and 
water  safety  (i.e.,  nitrite  assay  in  hot-pot  soup,  bacterial  detection  in  water,  and  resazurin  assay  in  milk).  Their  results  strongly 
demonstrate the suitability of both bamboo and bamboo–wood hybrid materials for also monitoring meat safety. 
Cotton,  commonly  used  in  everyday  life  for its benefits in liquid absorption, has also not yet been developed into a fully realized 
substrate  platform.  However,  the  absorptive  capacity  of  cotton  has  sparked  attention  from  some  researchers  given  its  potential 
POC  applications.  Lin  et  al.  [53,54]  have  introduced  a  cotton-based  detection  device  with  fluid  paths  for  effective  sample 
delivering.  This  device  uses  a  specific  type  of  cotton  with  a  hydrophobic  exterior  and  hydrophilic  interior,  which  is  capable  of 
delivering semi-quantitative and sensitive results, while also mitigating common risks of contamination. 
Thread,  a  fibrous and porous material, can readily be made into a semi-quantitative or quantitative detection device. As described 
in  the  research  of  Li  and  colleagues  and  of  Reches  and  colleagues  [55,56],  the  wicking  ability  of  thread  can  be combined with 
plasma  oxidation  or  other  specially  selected  materials  (i.e.,  mercerized  cotton,  which  could  attain  satisfactory  wettability)  to 
achieve  adequate  fluid  transportation.  Thread-based  devices  can  be  made  by  applying  sewing  techniques  –  weaving,  twisting, 
encapsulation  of  tape,  knots,  and  incorpo-  ration  of  gel  particles  into  the  thread – to provide microfluidic manipulation capacity 
[49].  Lin  et  al.  demonstrated  a  combination  design  that  employed  cotton  as  a  flow  channel  and  chromatography  paper  as  a 
reaction  zone  to  improve  the  quality  of  colorimetric  results  [53,54].  This  concept  still  requires  further  development,  but 
nonetheless shows promise as a potential platform for valuable detection functions. 
Smartphone-Based Technologies As a rapidly developing, recently emergent field, smartphone-based technologies have found 
success when merged with POC devices; this success has laid the foundation for further exploration, particularly with regards to 
food safety [11,13,24]. The combination of widespread wireless networks, robust computational processors, high-quality optical 
sensors, GPS receivers, wi-fi adaptors, chargeable and energy-efficient batteries, visual and touch-friendly displays, together with 
multiple customized applications, all of which are integrated into a portable, multifunctional, pocket-sized device, makes 
smartphones an exciting and ideal facilitator for POC devices (Figure 2A). Smartphones can be easily integrated with existing 
POC detection devices – in particular, paper-based analytical devices or hydrophilic-based detection devices – to meet the needs 
of both scientific and commercial applications in outbreak control, food chain and regulatory inspection, specific needs services 
for patients, and chemical detection [11,13,24]. In addition, they can be deployed in many places including the commercial 
sector, emergency room/inpatient healthcare settings, and in remote or underdeveloped rural regions. 
The  current  methods  for  ensuring  food  safety  rely  on  routine,  but  highly  resource-intensive,  laboratory-based  examination  of 
chemicals  and/or  pathogens.  In  remote  areas  where  resour-  ces  are  scarce,  sending  specimens to a centralized laboratory, where 
specialists  must  interpret  data,  can  be  difficult.  Smartphones,  by  contrast,  circumvent  these  logistic  challenges  via  on-  site  or 
remote  confirmation  of  detection.  Smartphones  can  double  as  colorimetric  or  fluoro-  metric  readers,  which  are  capable  of 
detecting  various  chemical  compounds,  nucleic  acids,  proteins,  and  metabolites.  In  addition,  they  may  even  be  used  as  visual 
microscopes.  Two  different  groups  [57,58]  demonstrated  the  use  of  hybrid  smartphone–integrated  POC  detection  devices  for 
chemical  detection.  In  a  prototypical  case  using  smartphone-based  devices,  Wei  and  coworkers  [59]  created  and  populated  a 
mercury  contamination  map  that  included  over  50  locations  in  California,  fully  demonstrating  the  light  weight,  flexibility,  and 
portability of 
Trends in Biotechnology, April 2017, Vol. 35, No. 4 
297 
 
smartphone-based  platforms. This approach integrated a small opto-mechanical attachment with an on-board smartphone camera, 
together  with  a  plasmonic  gold  nanoparticle,  to  detect  mercury  (II)  ion  concentration,  by  using  an  aptamer-based  colorimetric 
transmission  assay.  The  image  acquired  from  the  attachment  was  then  processed  through  the  use  of  a  software  application 
installed  on  the  smartphone.  Despite  being  lightweight,  compact,  portable,  and  mobile,  the  device  system  achieved  a  limit  of 
detection  of  <3.5  ppb.  Shen  and  colleagues  [60]  demonstrated  a  method  for  color  quantification  of  a colorimetric assay using a 
smartphone.  To  avoid  any  chance  of  yielding  biased  images  autocorrected  by  the phone, a reference chart with 12 color regions 
was  created  for  reproducible  color  quantification  despite  different  lighting  conditions.  The  color  reference  chart  served  as  a 
stabilizing landmark in a built-in algorithm, and a smartphone software application subsequently integrated the multiple functions 
into  a  straightforward output reading, thus creating an easy-to-use device that did not require complex user training. Current POC 
platforms  have  successfully  detected  pesticide  residue  such  as  paraquat  and  organophosphorus.  Major  challenges  for  POC 
platforms  include  (i)  developing  POC  platforms  capable  of  multiplex  testing;  (ii)  enhancing  specificity;  (iii)  improving  storage 
duration;  (iv)  enhancing  user-friendliness,  and  ease  of  operation  and  learning;  (v)  enhancing  the  signal-to-noise ratio to remedy 
the  influence  of  background  light  on  smartphone  cameras  (one  approach  would  be  for  researchers  to  use  a  box  to  reduce 
background noise during image capture). 
Continued  development  will  require  the  integration  of  further  interface  apparatuses  in  addition  to  detection  devices  and 
smartphones,  but  facilitating  such  integration  may  prove  costly.  Outside  the  laboratory,  test  operation  complexity, 
reproducibility,  and  reliability  all  become  significant  hurdles  to  overcome.  For  example,  further  development  of  sterilization 
methods  for  sampling  interfaces  remains  essential.  In  many  areas that are affected by lack of resources, wireless networks suffer 
from  poor  connectivity  and  signal  quality,  which  diminishes  the  always-  connected,  rapid  storage  and  transfer  advantages  of 
smartphones.  Despite  the  low  cost  of  manufacturing  paper-based  analytical  devices,  complex  sample  preparation  and 
improvement  in  specificity  remain  technical  challenges  that  may  drive  up  costs.  This  concern  is  in  addition  to  add-ons  and 
multiplexing capabilities. 
Summary and Future Perspectives Devices intended for POC use can provide rapid and sensitive results in the realm of food 
safety. Presently, POC detection devices have been developed and refined mainly for medical diagnostics in academic research 
and for providing medical services. In the past decade, however, hydrophilic materials (e.g., paper, cotton, and thread), 
plastic-based platforms, and smartphone-integrated technologies have been developed for variable applications and differ- ent 
fields, including animal health, food safety, industrial needs, therapeutic monitoring, and environmental assurance. While these 
substrate materials demonstrate a strong potential for application in environmental monitoring and food safety protection, three 
important needs remain unmet: (i) standardization of a universal protocol, (ii) a mature, commercialized kit with multiplexing 
features, and (iii) the systemic integration of fabrication, results analysis, and recording. While current researchers have 
introduced devices with high sensitivity and low detection limits, real-life implementation remains elusive because of the lack of 
large-scale, in- field data and repetitive quality assessment. To adapt to different measurements for various scenarios, a biomarker 
detection kit should be designed to serve various purposes. Two possible examples include a heavy metal detection kit designated 
for securing water safety that has the capacity to detect multiple toxic metals, and a bacteria kit that could detect food-borne 
diseases including the detection of multiple diarrhea-causing bacteria. Fortunately, smart- phones have become functionally 
robust and capable of running powerful mobile applications that can perform on-site, in-field analysis, while providing swift 
transfer and storage of data to help to facilitate comparisons with both previous and ongoing records (Figure 2A). A primary 
298 
Trends in Biotechnology, April 2017, Vol. 35, No. 4 
 
Outstanding goal for any POC testing device is user-friendliness (Figure 2B). The provision of rapid and easily 
Questions 
read and interpreted results is crucial to the success of any such approach. A clear 'yes-or-no' 
Can food safety be 
monitored without manifestation, or other simple visualization (e.g., distance-based, count-based, semi-quanti- 
reliance on a centralized laboratory? 
tative  colorimetric  manifestation)  can  reduce  the  costs  that  would  otherwise  be  incurred  by  specialized  personnel  training.  The 
subjective  difference  of  interpretation  bias  may  yield  results  that  prompt  doubts  not  only  within  the  academic  field  but  also 
among the industry, regulatory 
How can a universal protocol be imple- mented for POC testing devices for food safety and environmental authorities, and 
individual consumers, thus harming the credibility of measurement and 
monitoring? recording. 
Thus, the most promising trend towards the analysis of POC results includes the use of cameras, camera phones, and smartphones 
to standardize colorimetric parameters, thereby avoiding bias, and ensuring the reliability of the test. Although such devices may 
require a waiting time for approval from authorities, the trend towards combining smartphones with 
Given economic and political limita- tions, can a mature, commercialized kit with full multiplexing features be viably developed 
in the near future? microfluidic paper-based analytical devices is inevitable. With these devices, outbreaks of food- borne hazards 
can be mitigated because infectious agents, toxic chemicals, toxic metals, and 
With the increased 
rapidity of test pesticide residues can be swiftly identified and quantified. The demand for POC devices capable of monitoring 
food safety is an ever-growing and inevitable march that should lead 
results coming from POC testing devi- ces, how can we ensure the systemic integration of fabrication, results anal- to the 
integration and expansion of low-cost, portable, and reliable monitoring that will be 
ysis, and recording? 
available to all. 
What are the real-world limitations on 
Acknowledgments This research is financially supported by Chang Gung Memorial Hospital, Taiwan (G3S0013, G3E0361, 
G3D0072, 
detection limits and sensitivity, given the lack of large-scale, in-field data, and repeated quality assessment? G3F0601), Taichung 
Veterans General Hospital, Taiwan (TCVGH-1056904C, TCVGH-DYU1058302, TCVGH- 1066904C) and the Ministry of 
Science and Technology of Taiwan (104-2628-E-007-001-MY3, 105-2221-E-007- 053-MY3, 105-2221-E-182A-003). We also 
thank Dr Yu-Ping Wang (Department of Radiology, Taichung Veterans General Hospital, Taiwan) for his delicate drawings for 
illustration, and Dr Chun-Yuan Wang (Department of Ophthalmol- ogy, Taichung Veterans General Hospital, Taiwan) for his 
valuable suggestions. 
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