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Sensory development for heavy metal detection

A review on translation from conventional analysis to field-portable sensor

Mukherjee, Subhankar; Bhattacharyya, Soumyadeb; Ghosh, Koustuv; Pal, Souvik; Halder, Arnab; Naseri,
Maryam; Mohammadniaei, Mohsen; Sarkar, Subrata; Ghosh, Alokesh; Sun, Yi
Total number of authors:
11

Published in:
Trends in Food Science and Technology

Link to article, DOI:

10.1016/j.tifs.2021.01.062

Publication date:
2021

Document Version
Peer reviewed version

Link back to DTU Orbit

Citation (APA):
Mukherjee, S., Bhattacharyya, S., Ghosh, K., Pal, S., Halder, A., Naseri, M., Mohammadniaei, M., Sarkar, S.,
Ghosh, A., Sun, Y., & Bhattacharyya, N. (2021). Sensory development for heavy metal detection: A review on
translation from conventional analysis to field-portable sensor. Trends in Food Science and Technology, 109,
674-689. https://doi.org/10.1016/j.tifs.2021.01.062

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 Sensory Development for Heavy Metal Detection: A Review on Translation

from Conventional Analysis to Field-Portable Sensor

Subhankar Mukherjeea, Soumyadeb Bhattacharyyaa, Koustuv Ghosha, Souvik Pala, Arnab Halderb,c,

Maryam Naserib, Mohsen Mohammadniaeib, Subrata Sarkara, Alokesh Ghosha, Yi Sunb,*, Nabarun

Bhattacharyyaa,*

a
Agri and Environmental Electronics (AEE) Group, Centre for Development of Advanced

Computing (C-DAC), Sector – V, Salt Lake, Kolkata, West Bengal – 700091 (IN)

b
Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs.

Lyngby, Denmark

c
Laboratory of Organic Electronics, Department of Science and Technology, Linköping

University, 60174 Norrköping, Sweden

*Corresponding authors
Yi Sun, Ph.D.
Ph: +45 26673998;
Email: [email protected]

Nabarun Bhattacharyya, Ph.D.

Ph: +91-33-2357 6309, Fax: + 91-32-2357 5141
Email: [email protected]
Abstract:

Background

In recent decades, contaminations with heavy metals ions have adversely affected environment,
food safety and human health. Heavy metals, leaching to water sources from the industrial
effluents, are able to enter into the aquatic and food chains of humans and animals from a variety
of anthropogenic sources.

Scope and Approach

Heavy metal detection has been an intensive area of research today. Both laboratory-based
analytical instruments and innovative sensor devices like electronic nose, electronic tongue and
bio/ chemical sensors have increasingly emerged to meet the demand for legislative actions on
environmental pollution control and early warning. These evolving technology and developments
particularly in the area of nanotechnology and sensors have become key contributing factors in
heavy metal detection.

Key Findings and Conclusions

This endeavor aims at exploring this field in details to understand the key principles behind this
flourishing science and summarize the recent development in heavy metal detection technologies.
This article also gives a brief review of commercially available portable devices that has the
potential to become the next gold standard instruments in heavy metal detection.

Keywords: Heavy metal; Analysis; Nanotechnology; Sensors; Portable devices; Data analytics;

2
 1 1. Introduction

2 Water affects various aspects of the society, such as human/animal healthcare, food chain, tourism

3 industry (Mikhailenko, Ruban, Ermolaev, & van Loon, 2020), etc., therefore improving the water

4 quality can boost the economic growth of a nation, and contribute greatly in poverty reduction.

5 Having access to clean and safe water for daily consumption i.e. drinking, cooking, personal

6 hygiene and sanitation facilities is the fundamental and basic right of human (Samra, Crowley, &

7 Fawzi, 2011). However, according to a report published by World Health Organization (WHO),

8 there are 785 million people who are in lack of even basic drinking-water service, and 144 million

9 people who are dependent on surface water (WHO, 2004d). Globally, at least 2 billion people use

10 drinking water sources that are contaminated (WHO, 2019). Contaminated water can transmit

11 diseases such as diarrhea, cholera, dysentery, typhoid, and polio (WHO, 2004d). In the last few

12 decades, due to the growing increase in industrialization and urbanization, the presence of heavy

13 metals poses a serious concern to human health. The focus on heavy metals and their detection has

14 been much discussed because of the excessive leaching of these non-biodegradable metals.

15 According to the recent report of the Central Water Commission (CWC), for the duration of May

16 2014 to April 2018, two-third of drinking water samples have been found contaminated and

17 polluted by deadly heavy metals (Koshy, 2019). Iron (Fe), lead (Pb), nickel (Ni), chromium (Cr),

18 cadmium (Cd) and copper (Cu) are registered as the major contaminants in the samples. Not only

19 in water, heavy metal toxicity is also very common in food . This is mainly caused by irregular

20 irrigation, sewage, unhygienic food processing and improper storage of the food. There are several

21 instances where measurable amounts of heavy metals are found in various food products.

22 Therefore, detection of heavy metals in food products is a serious issue that is being addressed by

3
23 researchers throughout the world. These toxic metals can be detected though conventional testing

24 methods as well as with the help of modern innovative sensors.

25 Heavy metals are broadly defined as metals having high relative density (>5 g cm-3) with large

26 atomic masses compared to water to cause serious toxicity when present in trace levels in biotic

27 environment. The most toxic heavy metals are mercury (Hg), Cd, arsenic (As), Cr, thallium (Tl)

28 and Pb, since they can cause adverse health effects even at the low level of concentrations.

29 Although, less toxic heavy metals such as Fe, Cu, zinc (Zn), cobalt (Co) and manganese (Mn)

30 which are found in our body and extensively used by various enzymes can only cause serious

31 problems if they present above certain threshold levels.

32 Arsenic in water is mostly present in the more toxic inorganic form (> 99%), and naturally exists

33 at high levels in a number of countries’ groundwater. Arsenic contaminated water used for

34 drinking, food preparation and irrigation of food crops poses the greatest threat to public health.

35 In the 1980s, it was recognized that the As contaminated groundwater in the state of West Bengal

36 in India caused illness and death, and threatened the health of millions of people (UNICEF, 2018;

37 WHO, 2019). As the testing for arsenic was conducted in other countries, it became apparent that

38 As contamination extended around the world including Taiwan, Hungary, Chile and Argentina.

39 Pb, on the other hand, is a cumulative toxicant affecting multiple body systems and is particularly

40 harmful to young children. There is no level of exposure to Pb that is known to be without harmful

41 effects. Another report published by Unites States Environmental Protection Agency (US EPA)

42 states that Cd is highly persistent in water and has potential for bio-accumulation in biotic

43 organisms (EPA, 2016). Cd enters the environment primarily through leaching from landfill and

44 industrial effluents. Moreover, Cr as one of the major toxic heavy metals in water is also more

4
45 dangerous in its hexavalent state. Cr has two forms - trivalent and hexavalent, both of which needs

46 to be considered for proper assessment of associated health risks in drinking water.

47 Until today, the conventional techniques remain the gold standard for quantification and

48 monitoring of heavy metal ions. The main detection techniques include atomic absorption

49 spectroscopy (AAS) (de Almeida Pereira, de Amorim, & da Silva, 2004), flame or furnace

50 spectroscopy (Jianrong Chen & Teo, 2001), inductively coupled plasma mass spectrometry (ICP-

51 MS) (N. Zhang, Suleiman, He, & Hu, 2008), energy dispersive X-ray fluorescence (EDXRF)

52 spectrometry (Menéndez-Alonso, Hill, Foulkes, & Crighton, 1999), etc.. Unfortunately, these

53 conventional analysis systems cannot meet the needs of fast detection (Kawamura & Miyata,

54 2016). Although conventional techniques are highly selective and sensitive to nanogram level of

55 heavy metals, most of them lack field portability and require skilled workforce and time to operate

56 (Luo, Wang, Wang, Huang, & Zhang, 2016). Moreover, their running costs are also high. With

57 the dramatic elevation of heavy metal pollutions due to the industrial development and the fact

58 that these heavy metals, if remain unmonitored properly in the environment, can bio-accumulate

59 in the environment causing toxicity to existent life forms, there is a high demand for the

60 development of a fast, rapid, portable and on-spot automated detection system.

61 In this endeavor, the toxicity limits and associated health risks of the most hazardous heavy metal

62 ions have been discussed and different detection systems have been considered. Though there are

63 a number of review papers focusing on the specific detection techniques or toxicity mechanisms,

64 here, we aim to provide a comprehensive report covering wide ranges of techniques from

65 conventional to newly-developed approaches for the fabrication of ideal devices. Finally, some

66 commercialized field-portable instruments are mentioned and their pros and cons are discussed.

5
67 2. Heavy Metals: Toxicity limits and associated health benefactor/risks

68 In general, heavy metals are naturally occurring in the environment, and due to their increase in

69 biotic flora and fauna in recent years, the regulatory authorities are to decide some essential

70 standards for safe consumption of these heavy metals (Singh, Gautam, Mishra, & Gupta, 2011).

71 Table 1 illustrates a list of different global and national regulatory authorities that determines and

72 regulates these standards for safe consumption in drinking water. This list also highlights the

73 difference in threshold limits due to the geographical variation and consumption limits of different

74 population in drinking water.

75

76

6
77 Table 1: Maximum permissible limits of various heavy metals according to different regulatory authorities
Sl. Heavy FSSAI WHO CODEX EU FDA Associated Health Risk References
No. Metal (mg L-1) (mg L-1) (mg L-1) (mg L-1) (mg L-1)
• Nausea, Vomiting, Diarrhea (ATSDR,
• Muscle cramps 2012; CODEX;
• Salivation EPA, 2016;
1. Cadmium 0.003 0.003 0.003 0.005 0.005 • Sensory disturbances FSSAI;
• Liver injury Jaishankar,
• Convulsions Tseten,
• Shock and renal failure
Anbalagan,
• Encephalopathy
Mathew, &
• Watery diarrhea that
contains blood Beeregowda,
2. Arsenic 0.05 0.01 0.01 0.01 0.01 • Thickening of the skin 2014; Khan,
• Darker skin, Abdominal pain Khan, Khan,
• Diarrhea, Heart disease Qamar, &
• Numbness, Cancer Waqas, 2015;
• Abdominal pain, Storelli, 2008;
Constipation, Headaches, WHO, 2003a,
Irritability, Memory 2003b, 2004a,
problems
2004b, 2004c,
• Inability to have children,
2004d, 2006,
3. Lead 0.01 0.01 0.01 0.01 0.005 • Tingling in the hands and
feet 2017, 2019)
• Intellectual disability
• Behavioral problems
• Anemia, Seizures
• Coma
• Behavioral or psychiatric
4. Chromium 0.05 0.05 - 0.05 0.100 conditions
• Depression

7
 • Anxiety, Schizophrenia
• Kidney and liver diseases.
• Nausea
• Vomiting
5. Zinc 15 3.00 - 5.00 5.000
• Cramps
• Diarrhea
• Vomiting,
• Hematemesis (vomiting of
blood)
• Hypotension (low blood
pressure)
6. Copper 1.5 2.00 - 2.00 1.000 • Melena (black "tarry" feces)
• Jaundice, Gastrointestinal
distress.
• Hemolytic anemia
• Damage of the liver and
kidneys.
• Stomach pain,
• Nausea and vomiting
7. Iron 0.3 2.00 - 0.2 0.300 • Bloody vomiting may occur.
• Metabolic acidosis,
• Hypovolemic shock
• Harmful effects on central
and peripheral nervous
systems
• Tremors
8. Mercury 0.001 0.006 0.001 - - • Insomnia and memory loss
• Headaches and cognitive and
motor dysfunction
• Effects on the nervous,
digestive and immune

8
 systems, lungs and kidneys,
and may be fatal
• Chronic bronchitis
• Reduced lung function
• Cancer of the lung and nasal
9. Nickel 1.5 0.02 - 0.02 0.1 sinus
• Allergy
• Cardiovascular and kidney
diseases
• Fatness
• Glucose intolerance
• Blood clotting
• Skin problems
10. Manganese - 0.4 - 0.3 0.05
• Lowered cholesterol levels
• Skeleton disorders
• Birth defects
• Neurological symptoms
• Irritation of the eyes, skin
and lungs
• Lungs disease
11. Antimony - 0.02 0.005 0.005 0.006
• Vomiting
• Diarrhea
• Stomach ulcers
• Vomiting and nausea
• Vision problems
12. Cobalt - 0.05 - - - • Heart problems
• Thyroid damage
• pneumonia
78

9
79 FSSAI: Food Safety and Standards Authority of India; WHO: World Health Organization; CODEX: Codex Alimentarius Commission
80 a body under Joint FAO/WHO Food Standards Programme in Rome; EU: European Union; USFDA: United State Food and Drug
81 Administration

10
 82 3. Detection techniques

83 3.1. Conventional detection techniques

84 Some conventional detection techniques for common heavy metals quantification are discussed

85 here. Cd can be conventionally detected by AAS and flame or furnace spectroscopy with detection

86 limits of 5µg L-1 and 0.1µg L-1 (Dadfarnia, Assadollahi, & Shabani, 2007; WHO, 2004a). Shahlaei

87 and Pourhossein used a bio-adsorbent of A.niger to pre-concentrate the analytes to achieve

88 nanogram limit of detection (LOD) using electrothermal atomic absorption (ETAAS). Their

89 experiment showed LOD value for As2O3 and As2O5 was 1ng L-1 and 5ng L-1, respectively

90 (Shahlaei & Pourhossein, 2014).

91 The most commonly used methods for Cr detection in water are laboratory-based methods, such

92 as AAS and MS. Yuan et al. have used sodium diphenylamine sulfonate (DPH) reagents to detect

93 Chromium through spectrophotometric techniques (Yuan, Fu, Wang, & Yuan, 2008). The pre

94 concentration, separation and determination of CrIII and CrVI have been achieved by Alonso et al.

95 (Menéndez-Alonso, et al., 1999). They used a combination of ion exchange media and EDXRF

96 spectrometry (Menéndez-Alonso, et al., 1999). Due to pre-concentration factor of 500, the LODs

97 were obtained as 0.3 mg L-1 for CrVI and 0.4 mg L-1 for CrIII. Luciano et al. also developed

98 methodologies for chromium detection in drinking water by ETAAS using permanent modifiers.

99 The best results obtained for chromium was with the use of rhodium permanent modifier. The

100 detection limit was of 0.2 µg l-1 for chromium (de Almeida Pereira, et al., 2004). Moreover, Zhang

101 et al. have synthesized a new chromium(III)-imprinted 3-(2-aminoethylamino) propyl tri-methoxy

102 silane (AAPTS)-functionalized silica gel sorbent with the help of a surface imprinting technique

103 and employed the same as selective solid-phase extraction material for speciation analysis of

11
104 chromium in environmental water samples prior to its determination by ICP-MS. Under the

105 optimized conditions, the detection limits were calculated to be 4.43 pg mL-1 and 8.30 pg mL-1 for

106 the two Cr species (N. Zhang, et al., 2008). Moreover, Beere et al. have developed an ion

107 chromatography system for the separation and determination of Cr (III) and Cr (VI) species in

108 aqueous samples, and very high sensitivity was achieved using a chemiluminescence post-column

109 reaction detector based on the catalytic oxidation of luminol. Detection limits were 0.05 and 0.1

110 μg l−1 for Cr(III) and Cr(VI) respectively (Beere & Jones, 1994).

111 AAS is the most widely used method for the determination of Zn. The detection limit of the direct

112 air–acetylene flame method is 50 µg L-1(Shabani, Dadfarnia, Moosavinejad, & Ahmadi, 2009).

113 Low concentrations can be measured by chelating Zn with ammonium pyrrolidine dithiocarbamate

114 and extracting it with methyl isobutyl ketone (detection limit 0.5 – 1 µg L-1). Tony et al. has

115 developed a rapid and sensitive flow injection analysis–atomic absorption spectrometric procedure

116 for the determination of Zn based upon on-line pre-concentration on a micro-column packed with

117 C18 material (Tony, Kartikeyan, Vijayalakshmy, Rao, & Iyer, 1999). Zn forms complexes with

118 5,7-dichlorooxine from weakly acidic or neutral solutions in the flow system and adsorbed on the

119 column. The respective detection limit was 0.5 ppb. Matusiewicz et al. has also developed a simple

120 method for the atomic absorption determination of Zn in river and estuarine water using two atom

121 trapping techniques: a water-cooled dual silica tube and a commercially available double-slotted

122 quartz tube mounted in an air-acetylene flame (Matusiewicz, Sturgeon, Luong, & Moffatt, 1991).

123 The detection limit was 0.3 ng ml−1 for Zn using a 2 min in situ pre-concentration time with the

124 dual silica tube atom trap, and 1.2 ng ml−1 for Zn using the double-slotted quartz tube. Cloud point

125 extraction (CPE) has been used by Chen et al. for the simultaneous pre-concentration of Zn after

126 the formation of a complex with 1-(2-thiazolylazo)-2-naphthol (TAN), and later analysis by flame

12
127 atomic absorption spectrometry (FAAS) using octyl-phenoxy-polyethoxy-ethanol (Triton X-114)

128 as surfactant (Jianrong Chen & Teo, 2001). The detection limit was 0.095 ng mL−1 for Zn.

129 The most important analytical methods for the detection of Cu in water are AAS with flame

130 detection, graphite furnace atomic absorption spectroscopy, inductively coupled plasma atomic

131 emission spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS) and stabilized

132 temperature platform graphite furnace atomic absorption (ISO, 1986, 1996; ASTM, 1992, 1994;

133 US EPA, 1994). The ICP-MS technique has the lowest detection limit, and the AAS technique has

134 the highest. LOD for the other three techniques range from 0.7 to 3 μg L-1 (WHO). Wen et

135 al. has proposed a new method based on dispersive liquid–liquid micro-extraction (DLLME) pre-

136 concentration using tetra-chloromethane (CCl4) as extraction solvent for the spectrophotometric

137 determination of Cu in water and food samples. Under the optimal conditions, the limit of detection

138 for Cu was 0.5 μg L-1 (Wen, Yang, Yan, & Deng, 2011). Cloud point extraction employing the

139 new reagent 6-[2′-(6′-methyl-benzothiazolylazo)]-1,2-dihydroxy-3,5-benzenedisulfonic acid as

140 complexing agent and Triton X-114 as the surfactant has been proposed by Lemos et al. for Cu

141 determination. Dilution of the surfactant-rich phase with acidified methanol was performed after

142 phase separation, and the Cu contents were measured by flame atomic absorption spectrometry

143 with a detection limit of 1.5 µg L−1 (Lemos, Santos, dos Santos, Vieira, & Novaes, 2007). Rahil-

144 Khazen et al. has used inductively coupled plasma atomic emission spectrometry (ICP-AES) for

145 the determination of Cu in human serum (Rahil-Khazen, Henriksen, Bolann, & Ulvik, 2000).

146 Detection limits was 0.014± 0.07 mmol L-1 for Cu. Coale et al. has described the process of

147 detection of Cu in sea water using a flow-injection method with chemiluminescence (CL) detection

148 (Coale, Johnson, Stout, & Sakamoto, 1992). The determination was based on the formation of a

149 complex between Cu and 1,10-phenanthroline and the subsequent emission of light during the

13
150 oxidation of the complex by hydrogen peroxide. They constructed a flow-injection manifold which

151 provides for the separation of Cu from the sea water matrix with a column of immobilized 8-

152 hydroxyquinoline. An on-line flow injection solid-phase extraction procedure was developed by

153 Yu et al. for trace Cu separation and pre-concentration with detection by flame atomic

154 spectrometry (H.-M. Yu, Song, & Chen, 2011). A novel adsorbent-silica gel bound dithizone

155 (H2Dz-SG) was prepared and used as solid-phase extraction of Cu from complex matrix. The

156 H2Dz-SG quantitatively adsorbs Cu ions, and the retained Cu is afterwards collected by elution of

157 10% (v/v) nitric acid. The detection limit of Cu was 0.2 μg L−1.

158 Fe in water can be determined by AAS (detection limit 1 μg L-1) or by colorimetric methods

159 (detection limit 5 μg L-1) (H.-M. Yu, et al., 2011). An automated shipboard analytical method for

160 determining Fe (III) in seawater has been developed by Obata et al. (Obata, Karatani, & Nakayama,

161 1993). The method was based on a combination of selective column extraction using chelating

162 resin and improved CL detection in a closed flow through system. In this method, Fe (III) in an

163 acidified sample solution was selectively collected on 8-quinolinol immobilized chelating resin

164 and then eluted with dilute hydrochloric acid. The resulting eluent was mixed with luminol

165 solution, aqueous ammonia, and hydrogen peroxide solution successively, and then the mixture

166 was introduced into the CL cell. The Fe concentration was obtained from the CL intensity. The

167 detection limit of Fe (III) was 0.05 nmol L-1. A long liquid waveguide capillary flow cell has been

168 successfully adapted by Zhang et al., to a gas-segmented continuous flow auto-analyzer for trace

169 analysis of iron in water (J.-Z. Zhang, Kelble, & Millero, 2001). Utilization of the long flow cell

170 significantly enhances the sensitivity of automated colorimetric analysis of Fe by the ferrozine

171 method that allows the accurate determination of nanomolar concentrations of iron in natural

172 waters. The advantages of this technique were low detection limit (0.1 nM), small sample volume

14
173 (2 mL), high precision (1%), and automation for rapid analysis of a large number of samples.

174 Sensitive visual and micro spectrophotometric methods have been developed by Kawakubo et al.

175 for field determination of trace iron in fresh water samples (Kawakubo, Naito, Fujihara, &

176 IWATSUKI, 2004). For the visual method, a water sample (0.45-µm filtrate acidified to 0.1 M

177 HCl) was placed in a glass vial and mixed with a reagent solution containing 1,10-phenanthroline,

178 sodium thiocyanate and 0.1 M HCl. Fe was extracted as pink ferroin thiocyanate with 1 mL of 4-

179 methy-2-pentanone. The sample up to 20 ml was added step-by-step, until the color of the extract

180 was detected visually. Without any special instrument or color standard, iron down to 0.001 mg l-
1
181 (0.025 µg) in a sample can be determined with an error of 20% in the field. Fernández et al. used

182 a suppressor column for calcium removal in the determination of Fe in water samples by collision

183 cell ICP-MS (Fernández, Alonso, & Sanz-Medel, 2004). Natural water samples may contain high

184 levels of calcium, which interfere in Fe measurements by forming CaO+ and CaOH+ polyatomics

185 that are not completely eliminated in the cell. In order to eliminate such calcium interferences on

186 Fe, a conductivity suppressor column from a conventional ion chromatography system was

187 connected between the pump and the ICP-MS nebulizer. Calcium removal by the suppressor

188 column was higher than 99.99% for calcium concentrations up to 1000 ppm (sample pH between

189 2.5 and 7). In order to avoid the simultaneous removal of Fe, water samples were previously spiked

190 with the chelating agent EDTA to form a negatively charged complex which is not destroyed in

191 the suppressor column.

192 Stančić, Z.et al. (2016) has showed the detection of heavy metals in the food samples of Croatian

193 city market, Varaždin through atomic absorption spectroscopic technique. Lettuce, carrot, red and

194 white potato, onion, common bean, and cabbage were analyzed for the presence of heavy metals

195 in them and the scientist had found 9 different heavy metals though analyzing the food samples

15
196 though AAS. Among the 9 heavy metals, Pb and Cd contamination was found to be mostly

197 common in red potato, beans and carrots (Stančić, Vujević, Gomaz, Bogdan, & Vincek, 2016).

198 Byers, H. L. et al. (2019) has also examined dried and wet consumable vegetable tissues for the

199 presence of Pb and other heavy metals through WD-XRF and/or portable ED-XRF spectroscopy.

200 They have analyzed both the dried and wet tissue samples of consumable vegetables and reported

201 the presence of Pb in them. They also have found the measurable concentrations of the Pb found

202 is relevant to the WHO standards (Byers, McHenry, & Grundl, 2019). Nisa, K. U. et al. (2020) has

203 reported the presence of heavy metals in certain food samples like Cabbage, Cucumber,

204 Cauliflower, Tomato and Lady finger, Banana, Water melon, Mango, peach, apple etc. through

205 Flame atomic absorption spectroscopy (FAAS). Deuterium background hollow cathode lamps

206 (double beam) was used for the detection of certain heavy metals like Pb, Cd, Fe, Cu, Co, Mn and

207 Ni etc. They have found the level of Ni to be higher than the toxicity level in cucumber along with

208 elevated level of Pb in several vegetables and fruits (Nisa & Khan, 2020). Erasmus, S. W.et al.

209 (2020) has evaluated the percentage of Pb contamination in turmeric powder by Fourier transform-

210 Raman (FT-Raman) spectroscopy. They analyzed the FT-Raman spectra by both univariate and

211 multivariate statistics. Analyzing the Raman peak at 840 cm−1 and through a correlation study

212 they have proposed a limit of detection (LOD) of 0.6% (Erasmus, van Hasselt, Ebbinge, & van

213 Ruth, 2020). Graphite furnace atomic absorption spectrometry (GFAAS) has been used by

214 GEORGESCU, I. M. et al. (2019) for Pb detection in non-animal food products. They have

215 reported that wine, fruits, cereals, vegetables and mushrooms samples containing a weaker Pb

216 contamination, while high contamination has been reported in fruit juice samples (GEORGESCU,

217 et al.). Not only that, wheat and barley samples were analyzed for the presence of toxic heavy

218 metals like Pb, Cd, As, Co, Hg, Ni etc. though ICP-MS/MS by Thabit, T. M.et al. (2020). The

16
219 samples were digested using microwave acid digestion prior to analysis via ICP-MS/MS. They

220 have reported that Pb and Cd as the most prevalent heavy metals were found in several samples

221 (Thabit, Shokr, Elgeddawy, & El-Naggar, 2020).

222

223

17
224 Table 2: Summary of conventional techniques for major heavy metal detection.

Heavy Sample pretreatment Methods of detection Detection limit References

metal
As3+ UV digestion and preconcentration using ETAAS 1 μg L-1 (Shahlaei & Pourhossein, 2014)
Aspergillus niger-activated charcoal as
biosorbent
Cr3+ pre-concentration using ion exchange media EDXRFS 0.4 mg L-1 (Menéndez-Alonso, et al., 1999)
Pyrolysis and atomization using rhodium ETAAS 0.2 µg L-1 (de Almeida Pereira, et al., 2004)
permanent modifier
Solid-phase extraction ICP-MS 4.43 ng L-1 (N. Zhang, et al., 2008)
Separation on a Dionex AS4A anion exchange CL 0.05 μg L-1 (Beere & Jones, 1994)
column
Zn2+ Preconcentration on a microcolumn of FAAS 0.2 µg L-1 (Shabani, et al., 2009)
immobilized Alizarin Red S on alumina
Chelating with 5,7-dichlorooxine AAS 0.5 μ L-1 (Tony, et al., 1999)
In situ pre-concentration with the dual silica tube AAS 0.3 μg L-1 (Matusiewicz, et al., 1991)
atom trap
CPE pre-concentration FAAS 0.095 μg L-1 (Jianrong Chen & Teo, 2001)
Cu2+ DLLME pre-concentration Spectrophotometric 0.5 μg L-1 (Wen, et al., 2011)
FAAS 1.5 µg L-1 (Lemos, et al., 2007)
CPE pre-concentration
ICP-AES 0.014 mM (Rahil-Khazen, et al., 2000)
Chelating 1,10-phenanthroline CL 0.4 nM (Coale, et al., 1992)
-1
solid-phase extraction FAAS 0.2 μg L (H.-M. Yu, et al., 2011)
3+
Fe selective column extraction CL 0.05 nM (Obata, et al., 1993)
225

18
226 3.2. Modified conventional techniques

227 Some conventional techniques are modified for the in-field sensing of heavy metals. They have

228 similar sensitivity as conventional techniques, but have higher degree of portability and rapidness.

229 Kunimura et al. has developed a portable total reflection X-ray fluorescence spectrometer for the

230 nano level detection of Cr (Kunimura & Kawai, 2007). The continuum X-rays emitted from the

231 low-power X-ray tube was used without monochromatizing them. The MDL for Cr was a few

232 nanograms or the level of 1013 atoms cm-2. Kumar et al. has designed and developed a cost-

233 effective, simple, sensitive and portable LED based fiber optic evanescent wave sensor for

234 simultaneously detecting trace amounts of chromium (Kumar, Lee, Vallabhan, Nampoori, &

235 Radhakrishnan, 2002).

236 A novel micro-cloud point extraction (MCPE) was developed by Ghasemi et al. as a fast, simple,

237 and economical pre-concentration method for spectrophotometric determination of Zn in water

238 samples (Ghasemi & Kaykhaii, 2017). In contrary to traditional cloud point extraction, this method

239 does not need heating. To achieve the cloud point in room temperature, the MCPE procedure was

240 carried out in brine. Triton X-114 was employed as a non-ionic surfactant and the analytes were

241 chelated by 4-(2-pyridylazo) resorcinol prior to extraction. Under the optimized condition,

242 calibration curve was found to be linear in the concentration range of 0.15-0.60 mgL-1 for Zn with

243 a limit of detection of 51.7 μg L-1. A high sensitive method of quantitative analysis for the

244 determination of Zn in the nutrition supplements has been developed by Weng et al. using a novel

245 water-soluble fluorescent sensor (Ghasemi & Kaykhaii, 2017). Under the optimized condition of

246 67 mM phosphate buffer, pH 7.4, and 5% (v/v) DMSO, the Zn concentration exhibited good linear

247 relationship with fluorescence intensity in the range of 7.5 × 10−8 to 2.5 × 10−5 M with the

19
248 detection limit of 1.5 × 10-8 M. The sensor revealed high selectivity to Zn comparing with other

249 metal ions except for Cd.

250 Quantitation technique of trace amounts of Cu (II) dissolved in natural water has been developed

251 by Gao et al. (Gao, et al., 2007). A novel detection approach named chromophore-decolorizing

252 with free radicals was developed for determination of trace heavy metal. Chen et al. has designed

253 a fluorescence resonance energy transfer (FRET)-mediated sensor, based on fluorescent polymeric

254 nanoparticles synthesized via a combination of a facile one-pot mini emulsion polymerization and

255 subsequently by surface modification technology. The nanoparticle-based dual-ion sensor can be

256 reversibly switched for multi-times by alternative addition of adequate Cu2+ or S2−, and was also

257 applicable in a relatively wide pH range (pH 4 - 10), exhibiting excellent long-term photo-stability

258 for Cu2+ detection (Jian Chen, et al., 2015).

259 Microfluidic paper-based analytical devices (μPADs) were used by Ogawa et al. to detect the iron

260 ion content in the water of a natural hot spring in order to assess the applicability of this process

261 to the environmental analysis of natural water (Ogawa & Kaneta, 2016). The μPADs were

262 fabricated using a wax printer after the addition of hydroxylamine into the detection reservoirs to

263 reduce Fe3+ to Fe2+, 1,10-phenanthroline for the forming of a complex, and poly(acrylic acid) for

264 ion-pair formation with an acetate buffer (pH 4.7). A novel colorimetric chemosensor containing

265 terpyridine was synthesized by Liang et al. that showed high selectivity and sensitivity for Fe(II)

266 and Fe(III) ions in neutral aqueous solution in the presence of other metal ions such as Cd2+, Cr3+,

267 Zn2+, Co2+, Ni2+, Cu2+, Pb2+, Na+, Ca2+, Mg2+, K+ and Ag+ (Liang, et al., 2007). Upon the addition

268 of Fe2+or Fe3+, the sensor displayed a unique new peak around 567 nm in its absorption spectra,

269 and the color of the solution changed from light yellow to light magenta. Zhao et al. developed

270 Polyamine-functionalized carbon nanodots for the detection of Fe (II) (Lixia Zhao, et al., 2014).

20
271 Branched poly(ethylenimine)-functionalized carbon dots (BPEI-CDs) are used as a novel CL

272 probe in alkaline solution for rapid detection of Fe (III) ions with high sensitivity and selectivity.

273 A possible CL mechanism was studied by UV-Vis, fluorescence, CL, FTIR, XPS and EPR

274 spectroscopy. An eco-friendly and simple fluorescent nitrogen-doped carbon quantum dot (N-

275 CQD) biosensor was synthesized by Lv et al. via a hydrothermal method using erhanediamine

276 (EDA) and citric acid (CA) as precursors (Lv, et al., 2017). The surface functionalization of N-

277 CQDs exhibited a bright blue emission under the excitation wavelength of 350 nm. As-prepared

278 N-CQDs were further applied in Fe (III) detection. Spectroscopic data indicated that fluorescent

279 carbon-based nanomaterials displayed a sensitive response to Fe3+ in the range of 0.5–1000 μM as

280 a fluorescence sensor in real environmental samples. A novel rhodamine-based dual probe Rh-2

281 for trivalent ferric ions (Fe3 +) was successfully designed by Luo et al. and synthesized, which

282 exhibited a highly sensitive and selective recognition towards Fe3 + with an enhanced fluorescence

283 emission in methanol-water media (v/v = 7/3, pH = 7.2) (Luo, et al., 2016). The probe Rh-2 could

284 be applied to the determination of Fe3 + with a linear range covering from 3.0 × 10-7 to 1.4 × 10-
5
285 M and a detection limit of 1.24 × 10-8 M.

286 3.3. New age detection techniques

287 In the era of fast growing technology, rapid, high-throughput and field portable sensing

288 instruments are much widely accepted due to their point-of-care application and low cost. To meet

289 the high demands, the on-site portable sensors have been developed much rapidly. Though the

290 technology yet lacks sensitivity and selectivity comparative to conventional methods, they have

291 the potential to become primary pointof-care devices to accumulate data for sorting samples that

292 need further attention.

21
293

294 Figure 1: Block diagram of a biosensor.

295 This section comprises of a brief review of the new advancement in methodologies for the

296 detection of heavy metals with the use of chemical and biosensors. The transducer or the detector

297 transform one signal into another one, and works in a physicochemical way - optical, piezoelectric,

298 electrochemical, electro CL etc. signals resulting from the interaction of the analyte with the

299 chemical or biological element, to easily measure and quantify the target analyte. Chemical or bio-

300 sensory devices fulfill all the criteria that the conventional devices for heavy metal detection lack.

301 Biosensors and chemical sensors are very much rapid, require minimum skill to operate, field

302 portable, cost effective (Ronkainen, Halsall, & Heineman, 2010). On spot rapid detection of

303 analyte is the main criterion that makes the biosensors and chemical sensors more preferable than

304 the time consuming, costly conventional detection techniques.

22
305 There are various types of chemical and biosensors that are being applied to detect heavy metal

306 contamination in water nowadays, which include ion imprinted sensors (Haupt & Mosbach, 2000),

307 DNA aptamers (Patil, Rhodes, & Burgess, 2005), RNA-mediated biosensors (Velasco-Garcia &

308 Missailidis, 2009), enzymatic biosensors (C. Chen, et al., 2013), protein-mediated biosensors

309 (Bistolas, Wollenberger, Jung, & Scheller, 2005) etc.. Among them, use of ion imprinted

310 electrochemical sensors, aptamer biosensors and enzymatic biosensors based on DNAzymes are

311 more frequently seen (Y. Lu, 2002). A large variety of ion imprinted electrochemical sensors are

312 available and can be easily modified to detect analytes with very low cost and minimum amount

313 of time and labor (Yola, Eren, & Atar, 2015). Aptamers being single stranded DNA are to be

314 handled more cautiously, but they are very much selective to the analyte like heavy metals and

315 also modifiable with respect to the detection technique, i.e colorimetry or fluorimetry (Yola, et al.,

316 2015). Moreover, enzymatic biosensors are used widely to detect heavy metals which

317 preferentially use DNAzymes for specificity.

318 3.3.1. Enzyme-immobilized biosensors

319 Enzyme-based biosensors have been exploited for heavy metal ions detection extensively during

320 last few decades. Biosensors use enzymes which are immobilized on the transducer surface and

321 act as a bridge between the analyte and transducer. These type of sensors have an advantage of

322 high sensitivity and selectivity for heavy metals detection. The enzymes are generally inhibited in

323 the presence of heavy metals. This interaction is very specific for particular ions and hence has an

324 enhanced signal generation. The enzyme is chosen based on their ability to transfer electrons.

325 According to Ilangovan et al., sol-gel-immobilized-urease conductometric biosensor on a thick

326 film interdigitated electrode was developed (Ilangovan, Daniel, Krastanov, Zachariah, &

23
327 Elizabeth, 2006). The biosensor can be used for heavy metal ions determination in liquid samples.

328 The biosensor exhibited good response to changes in urea concentration within the range of 1 mM

329 to 15 mM. After standardizing the sensor for Urea, the biosensor has been used to determine the

330 heavy metal ions of different concentrations. The heavy metals ranging from 0.1 mM to 10 mM

331 could be detected. Among the three metals used, the amount of inhibition is found to be more in

332 Cd, followed by Cu and Pb. The sensitivity was 1 mM in the spectrophotometric technique and 5

333 mM in the electrical method. Moyo used horseradish peroxidase (HRP) biosensor to detect Zn ions

334 in aqueous solutions (Moyo, 2014). Maize tassel-multiwalled carbon nanotube (MT-MWCNT)

335 composite has been used as a matrix for physical adsorption of HRP onto the surface of a glassy

336 carbon electrode through electrostatic interactions. The HRP/MT-MWCNT biosensor was applied

337 for the detection of Zn2+in aqueous solution. The biosensor designed was able to determine Zn2+in

338 the range of 0.35 - 12 mg L-1 with a detection limit of 7.5 µg L-1. The inhibition was found to be

339 reversible and uncompetitive when data was modeled using the Dixon and Cornish-Bowden plots.

340 The biosensor was found to have good repeatability, reproducibility and high selectivity. The

341 developed biosensor can be used to detect other HRP inhibiting trace metal ions.

342 Recent advances in this field suggest the use of DNAzyme based technology. DNAzyme based

343 sensing can be applied as fluorometric, colorimetric and conductometric sensitivity. In Lu’s work,

344 nanoparticles were firstly coated with DNAzymes which have specific binding site for heavy

345 metals and also tagged with quencher, then incubated with substrate DNA strands tagged with

346 specific fluorophore (Y. Lu, et al., 2003). The quencher being in close proximity of the fluorophore

347 quenched the fluorescence, but when incubated with heavy metals, the DNAzyme efficiently

348 cleaves the substrate DNA, making the fluorophore free from the quencher, giving measurable

349 fluorescence that is described in Figure 2.

24
350

351 Figure 2: Schematic pathway for DNAzyme based optical detection of heavy metal ions.

352 A novel fluorescence biosensor based on DNAzyme for rapid, simple, sensitive and selective

353 detection of Pb ions was reported by Li and Lu (J. L. a. Y. Lu, 2000). It was reported that the

354 quantifiable detection range was from 10 nM to 4 µM and the selectivity was greater than 80-fold

355 for Pb divalent ions over other metal ions. Enzyme immobilized biosensors are sensitive and

356 selective but takes more time than aptamer based sensing or ion imprinted polymer based sensing.

357 Some other enzymatic sensors used for detection of heavy metals are listed in Table 3.

25
358 Table 3: Enzymatic sensors for detection of heavy metals.
S. Sensor configuration Transduction Metals Range of LOD References
No principal detected detection
1 GOx entrapped on novel Amperometric Hg2+, Cd2+, Hg2+(2.5-100 Hg2+(2.30nM), (da Silva,
ultra-thin poly(brilliant green) Pb2+, and Cr nM), Cd2+(10 - Cd2+( 1.75 nM), Ghica, &
(PBG) films electrodeposited (VI) 100 nM), Pb2+( 2.70 nM), Brett, 2020)
in ethaline DES on Pb2+(10 -120 Cr (VI) (2.44
multiwalled carbon nanotube nM), Cr (VI) ( nM)
(MWCNT) modified glassy 2.5-60 nM)
carbon electrodes (GCE)

2 Mg2+-dependent DNAzyme Fluorimetry Cu2+ 10 nM to 10μM 2 nM (W. Wu,

subunits, azide or alkaline Yu, Chen,
modified, immobilized on & Yang,
magnetic beads 2019)

3 Pb2+-specific DNAzyme pH metry Pb2+ 1.0–100 nM 0.91 nM (Tang, Xia,

immobilized on magnetic Tang,
beads, coupled to rolling Zhang, &
circle amplification (RCA) Zhou, 2019)

26
4 8–17 DNAzyme (the Electrochemical Pb2+ 10-13 to10-7 1.74 × 10-14 (Z. Yu, et
recognition element) mol·L−1 mol·L−1 al., 2019)
immobilized on carboxyl-
functionalized graphene
modified electrode

5 Pb2+-specific DNAzyme Electrochemical Pb2+ 1 pM –500 nM 0.32 pM (J. Zhao,

containing the capture probe Zheng, Gao,
(NH2-CP) immobilized on & Xu, 2018)
Au nanoparticles (AuNPs)-
loaded Fe3O4 nanocomposites
modified electrodes
6 Peroxidase-mimicking Chemiluminescen Hg(II) 12 - 600 nM 12nM (Gribas &
DNAzyme ce Sakharov,
2018)
7 GR-5 DNAzyme based Pb Colorimetric Pb2+ 0.01 to 100 μM 0.05 nM (H.-B.
ion strip biosensor (S/N = 3) and Wang, Ma,
1 nM (with Fang, Zhao,
naked eyes) & Hu, 2018)
8 Mg2+-specific DNAzyme Impedance Hg(II) 0.1 pM - 10 nM 0.042 pM (Cai, Xie,
(Mg2+-DNAzyme) for target biosensor Zhang,
cycling and hybridization Tang, &
chain reaction (HCR) Tang, 2017)
assembled DNA hydrogel for
signal amplification

27
9 fluorescent Cu2+sensor (PL- Fluorimetry Cu2+ 80 nM to 30 μM 21.1 nM (S. Wang, et
Cu 1.0) based on the al., 2017)
relationship between
glutathione/Cu2+and catalytic
activity of Pistol-like
DNAzyme (PLDz)
10 Cu2+-dependent DNA ligation Detection through Cu2+ 10 nM to10 µM 1 nM (Ming, Fan,
DNAzyme personaliized Jiang,
glucose meter Wang, &
Lv, 2017)
11 Cu2+-specific RNA-cleaving Fluorimetry Cu2+ 5 nM to 200 nM 1.6 nM (Huang &
DNAzymes (PSCu10) Liu, 2016)
12 Pb2+sensor based on Colorimetry Pb2+ 0.05 to 5 nM 20 pM (Yun, et al.,
DNAzyme and molecular 2016)
beacon (MB)
13 Urease and Glucose Oxidase Photoluminescenc Cu2+, Pb2+, 10 nM to 1 mM 10nM (Syshchyk,
based biosensor e Cd2+ Skryshevsk
y, Soldatkin,
&
Soldatkin,
2015)
14 Specifically modified Colorimetry Cu2+ 1 - 100 μM 1 μM (Vopálenská
Saccharomyces cerevisiae , Váchová,
strain immobilized in alginate & Palková,
beads 2015)

28
 15 Ultrathin polypyrrole–glucose Potentiometry Cu2+, Hg2+, Cu2+(0.079– 0.079 μM (Ayenimo &
oxidase (PPy–GOx) Cd2+and Pb2+ 16 μM), forCu2+, Adeloju,
potentiometric biosensor Hg2+(0.025– 0.025 μM for 2015)
5 μM), Hg2+, 0.024 μM
Pb2+(0.10– for Pb2+and
15 μM) and 0.044 μM for
Cd2+(0.04– Cd2+
62 μM)
359

29
360 3.3.2. Aptamers-based biosensors

361 Aptamers are classified as short chain nucleotides or oligos which are synthesized based on the

362 binding capability of the heavy metals. These oligos are generally synthesized by systematic

363 evolution of ligands by exponential enrichment (SELEX) methodology sequentially. The general

364 principle behind aptamer based sensing can be of either two types: one through the immobilization

365 of aptamer on the electrochemical electrode surface for enhanced sensitivity, and the other through

366 aptamer-based substrate such as gold nanoparticles (AuNP) reactions to generate colorimetric

367 response (Y. Wu, Liu, Zhan, Wang, & Zhou, 2012) (Figure 3).

368

369 Figure 3: Schematic representation of aptamer-based AuNP for heavy metal detection.

30
370 Both of which can be applied to determine the specific metals present in a sample. Their sensitivity

371 and LOD are generally not as low as the conventional techniques, but are quite efficient and high

372 through output in detection of contaminated samples. Their rapid and portable nature gives them

373 an advantage of being field portable technology. According to Wang and Si, they have used a

374 novel aptamer biosensor based on multi-walled carbon nanotube (MWCNT) which allows for

375 fluorescent energy transfer on binding with heavy metal such as Pb+2 ions and helps in their rapid

376 detection (Si, 2013). The LOD has been reported to be 20 nM for Pb detection. Similarly, aptamer

377 based technology has also been applied for the detection of cadmium divalent ions. Wu et al.

378 showed that Cd specific aptamer[Cd-4] could be used for the detection of Cd divalent ions by a

379 colorimetric reaction (Y. Wu, Zhan, Wang, & Zhou, 2014). The functionalized AuNP were

380 hybridized with poly (diallyldimethylammonium chloride) (PDDA) resulting in a duplex complex.

381 In presence of Cd divalent ions, the wine red solution of AuNP changed to blue due to no duplex

382 formation and hence no aggregation of AuNPs. The LOD for this was reported to be 4.6 nmol/L.

383 Lastly, electrochemical based aptasensors such as developed by Zhu et al. which is a sensitive

384 electrochemical aptasensor based on the carboxylic acid functionalized multi-walled carbon

385 nanotubes (MWNTs–COOH) and the direct electrodeposited AuNPs was developed for

386 Pb2+detection in water samples (Zhu, 2017). Methylene blue (MB) was selected as the G4-binding

387 indicator and redox probe. The sensor could detect Pb divalent ions in a range from 0.01 to 50

388 pmol L-1 with a detection of 4.3 fmol L-1.

389 Moreover, Zhou et al. has reported a method for the detection of Cu2+ ions by azide-and terminal

390 alkyne-functionalized gold nanoparticles in aqueous solutions using click chemistry (Y. Zhou,

391 Wang, Zhang, & Jiang, 2008). The catalyst, Cu (I), was conveniently derived from the reduction

392 of Cu(II) in the presence of sodium ascorbate. This method allows the naked eye, without the aid

31
393 of any advanced instrument, to visualize the presence of Cu2+ions by the aggregation of AuNPs as

394 a result of the Cu (I)-catalyzed conjugation between the two functional groups. This method for

395 the detection of Cu2+ ions relies on the Cu (I)-catalyzed 1,3-dipolar cyclo-addition of alkynes and

396 azides on the surface of functionalized AuNPs, that results in the aggregation of AuNPs. A simple,

397 rapid, sensitive and field-portable colorimetric technique for the determination of Cr(III) in

398 aqueous solution based on an aggregation-induced color transition (wine-red to blue, discernible

399 by the naked eye, easily measurable in the extinction spectrum of the particles) of

400 dithiocarbamate-modified N-benzyl-4-(pyridin-4-ylmethyl) aniline ligand (BP-DTC)

401 functionalized gold nanoparticles (AuNPs) has been developed (Liang Zhao, Jin, Yan, Liu, & Zhu,

402 2012). The method could be used to determine Cr (III) with a detection limit of 31 ppb and also

403 applied in the indirect determination of Cr(VI) in waste water. Some other aptamer based

404 detections of heavy metals are listed in Table 4.

405

32
406 Table 4: Aptamer-based detection of heavy metals.
S. N. Sensor configuration Transduction Metals Range of LOD References
principal detected detection
1 Pb(II)-aptamer(Apt) (D. Li, Yuan,
0.0005 - 0.46
Fluorimetry Pb2+ 0.25 nmol L-1 Li, Luo, &
μmol L-1
Jiang, 2020)
2 Hg2+specific aptamer with (Shijia Wu,
2.5 to 100
rolling circle amplification Colorimetry Hg2+ 1.6 nM Yu, He, &
nM
Duan, 2020)
3 Aptamer-functionalized gold (Gan, et al.,
nanoparticles (AuNPs) Colorimetry Cd2+ 2–20 μg L-1 1.12 μg L-1
2020)
4 DNA-based specific aptamer
probes labeled with ferrocene (Abu-Ali,
(or methylene blue) and thiol Hg2+and 0.1 to 1000 -1
Electrochemical 0.1 ng mL Nabok, &
groups at their 5′ and 3′ Pb2+ ng mL-1
Smith, 2019)
termini, respectively
5 G-quadruplex DNA aptamer
(S. H. Yu,
and an electrochemically 10−15 M to
Electrochemical Pb2+ 0.51 fM Lee, & Kim,
reduced graphene oxide 10−9 M
2019)
(ERGO) electrode
6 DNA aptamer-programmed
(H. Guo, et
self-assembly of CdTe Fluorimetry Hg2+ 0-100 nM 3.33 nM
al., 2019)
quantum dots
7 A mercury ion aptamer
electrochemical biosensor
0.01 to 500 (Liu, et al.,
based on a Thymine-Hg2+- Electrochemical Hg2+ 0.005 nM
nM 2018)
Thymine (T-Hg2+-T)
structure

33
 8 Triple-helix molecular switch
with 2-amino-5,6,7-trimethyl- (Pan, Li,
3+ 10 ng L-1 to -1
1,8-naphthyridine as the Fluorimetry As 5 ng L Zhou, &
10 mg L-1
signal indicator Chen, 2018)

9 Aptamer-based fluorescence (Sun, et al.,

biosensor Fluorimetry Hg2+ 2 to 160 nM 0.2 nM
2018)
10 Ultrasensitive aptamer
electrochemical biosensor
based on glass carbon 0.001 nM to (Liu, et al.,
Electrochemical Cd2+ 0.04995 pM
electrode (GCE) modified 100 nM 2017)
with chitosan (CS), gold
nanoparticles (AuNPs)
11 Hg2+specific aptamer 0.13 ng mL-1 (Z. Wu, et
Fluorimetry Hg2+ 0.13 ng mL-1
to 4 ng mL-1 al., 2017)
12 Hg2+specific aptamer 1 ng mL-1 to (Xiao, et al.,
Colorimetry Hg2+ 0.28 ng mL-1
32 ng mL-1 2016)
13 Hairpin structure of (Taghdisi,
complementary strand of Danesh,
aptamer, thionine, AuNPs Lavaee,
Electrochemical Pb2+ 0.6-50 nM 312 pM
Ramezani, &
Abnous,
2016)
14 Hg2+specific aptamer (J. Li, Sun,
1x10-14 mol
2+ 5.0×10−15 mol Wei, Zhang,
Electrochemical Hg L-1 to 2x10-12
L-1 & Zhang,
mol L-1
2015)
15 G-quadraplex aptamer (Qian, Shan,
specific to Pb2+ 0 to Chai, Chen,
Fluorimetry Pb2+ 0.6 nM
400.0 nM & Feng,
2015)
407

34
408 3.3.3. Ion Imprinted Sensors

409 Ion imprinted polymers contains specific cavities towards specific ions. Usually, the polymers are

410 synthesized by polymerization of monomer in presence of ions. The ions are sequentially extracted

411 from the polymer producing complementary cavities on the polymer matrix (Biju, Gladis, & Rao,

412 2003). Binding of specific ions in the cavities formed on the polymer matrix gives signals that can

413 be captured and analysed for further study. These ion imprinted polymers can easily be

414 polymerized on to the electrodes for electrochemical detection of analyte molecules. Recently ion

415 imprinted polymers are widely used in various applications like chemical separations (Dam &

416 Kim, 2008), catalysis (Wulff, 2002), or molecular sensors (Takeuchi & Haginaka, 1999) etc. Such

417 process of ion imprinted polymer based detection is illustrated in Figure 4.

418

419 Figure 4: Schematic representation of ion imprinted based sensing.

35
420 The transduction principle may be based on differential pulse voltammetry (DPV), square wave

421 voltammetry (SWV) or impedance spectroscopy, etc.. Owing to the attractive properties like

422 sensitivity, accuracy and selectivity including cost reduction, ion imprinting approach for heavy

423 metal ion detection has become promising alternative of conventional techniques (Sebastian &

424 Mathew, 2018).

425 Poly(diphenylamine-co-2-aminobenzonitrile) (p(DPA-co-2ABN)), a polyaniline derivative, was

426 electrodeposited on the surface of electrode and applied for detection of Cd2+ ions using DPV

427 (Philips, Gopalan, & Lee, 2012). p(DPA-co-2ABN) contains a cyano group which pre-

428 concentrates the Cd divalent ions to form a cyano chelation complex. This pre-concentration helps

429 in electrochemical detection of Cd divalent ions effectively with a LOD of 0.255 mg L-1. The

430 technique uses the principle of simple oxidation of metals due to applied voltage and simultaneous

431 increase in current due to increased electron flow which is proportional to the amount of metal

432 oxidized. This increase in current is seen as distinct peaks in between a constant potential range.

433 Hosseini et al. reported a highly selective and sensitive Zn ion-selective membrane electrode based

434 on N,N′-phenylenebis (salicylideaminato) as a new carrier (Hosseini, Abkenar, Ganjali, &

435 Faridbod, 2011). The membrane is composed of poly (vinyl chloride) (PVC), o-nitrophenyl octyl

436 ether (NPOE) as plasticizer, potassium tetrakis(p-chlorophenyl) borate (KTpClPB) as lipophilic

437 ionic additive, and N,N′-phenylenebis (salicylideaminato) as sensing material. The electrode

438 displays a Nernstian response to Zn2+ ions over a wide concentration range of 5.0 × 10− 7–

439 1.0 × 10− 1 M with the slope of 29.4 ± 0.2 mV per decade and a detection limit of 2.6 × 10− 7 M.

440 The sensor has a fast response time of < 10 s and it can be used in the pH range of 3.0–7.0 for at

441 least 2 months without any significant divergence in potential.

36
442 Gooding et al. has shown an electrochemical sensor for the detection of Cu ions that has a LOD

443 below 1 pM (Gooding, Shein, & Lai, 2009). This extraordinarily low limit of detection is achieved

444 in two ways. The first is to use SAM modified electrodes to give low background current where

445 electron transfer to the underlying polycrystalline electrode is achieved through gold nanoparticles

446 attached to the terminus of the SAM. The gold nanoparticles are modified with cysteine to allow

447 Cu accumulation. In the second way, the low LOD are achieved by the addition of cysteine-

448 modified nanoparticles to the sample solution, as well as the SAM modified electrode. The

449 complexation of Cu with the nanoparticles in solution causes them to aggregate with these

450 aggregates accumulating on the electrode. Thus a higher percentage of Cu in the solution is

451 collected at the electrode, giving the enhanced detection limits. Though this technique has yet to

452 be modified to achieve LOD values comparable to the conventional detection methods and near

453 the standard toxicity limits, the advantage of this technique is its high through output nature, cost

454 effectiveness and rapid screening of samples which can be further developed to make it portable

455 in nature. Some other ion imprinted sensors for detection of heavy metals are listed in Table 5.

456

37
457 Table 5: Ion imprinted sensors for detection of heavy metals.
S. N. Sensor configuration Transduction Metals Range of detection LOD References
principal detected
1 Magnetic ion-imprinted Electrochemical (Dahaghin,
polymer Kilmartin, &
Pb2+ 0.1–80 ng mL-1 0.05 ng mL-1
(Fe3O4@SiO2@IIP) Mousavi,
2020)
2 Fluorescent ZnSe quantum Fluorimetry
for Cd2+: 1 to 70 μg for Cd2+: 0.245 μg
dots (QDs) with ion (J. Zhou, et
Cd2+and Pb2+ L-1 and for Pb2+: 1 L-1 and for
imprinting technology -1 al., 2020)
to 60 μg L Pb =0.335 μg L-1
2+

3 Boronic acid functionalized Fluorimetry (X. Guo,

MoS2 quantum dot 0.005 to Huang, Wei,
Hg2+ 1.8 nmol L-1
41 μmol L−1 Zeng, &
Wang, 2020)
4 Blue and red dual channel Fluorimetry
for Cr3+ = 0.1 to for Cr3+ : 27 nM
dual emission carbon dots (H. Lu, Xu,
Cr3+ and Pb2+ 6.0 μM and for and for Pb2+:34
(DDCDs) as ion imprinted & Liu, 2019)
Pb2+=0.1 to 5.0 μM nM
fluorescence polymers
5 Nanoparticles of the Hg(II)- Electrochemical (Ganjali,
imprinted polymers Rahmani,
Shokoohi,
Hg(II) 0.06 to 25.0 nM 18 pM
Farmany, &
Khazaei,
2019)
6 Ion imprinted polymers Electrochemical
nanoparticles (nanoIIPs)
immobilised on the surface (Di Masi, et
Cu2+ 1.9 and 61 nM 74 pM
of gold screen printed al., 2019)
electrodes (SPAuE)

38
7 Ion-imprinted chitosan- Electrochemical (Shuping
graphene nanocomposites −9
1.0 × 10 to Wu, Dai,
Cr (VI) 6.4 × 10−10 mol/L
(IIP-S) 1.0 × 10−5 mol/L Cheng, & Li,
2018)
8 Cadmium (II) imprinted Electrochemical
0.008 to 0.05 μM (Dahaghin,
polymer nanoparticles (IIP-
and in the ranges Kilmartin, &
NPs) immobilized Cd2+ 1 × 10−4 μM
from 0.05 to Mousavi,
cadmium(II)-selective
0.80 μM 2018)
electrode
9 Acrylic acid as monomer Electrochemical (Sebastian &
and N,N methylene Zn (II) 1 to 5 ppm 1.32x10-4μM Mathew,
bisacrylamide as crosslinker 2018)
10 Itaconic acid-Pb2+complex Electrochemical
and ethylene glycol (Alizadeh,
dimethacrylate produced 1.0 × 10−11– Hamidi,
Pb2+ 3.8 pmol L−1
nano-structured ion 8.0 × 10−8 mol L−1 Ganjali, &
imprinted polymer Rafiei, 2017)
11 Cadmium (II) IIP particles Electrochemical
(Ivari,
in 2-nitrophenyloctyl ether
Darroudi,
as a plasticizer and 2.0 × 10−7–1.0 ×
Cd2+ 1.0 × 10−7 Zavar,
embedded in a 10−2 mol L−1
Zohuri, &
polyvinylchloride polymeric
Ashraf, 2017)
matrix
12 Ion-imprinted polymer (IIP) Electrochemical (Ghanei-
on the surface of reduced Motlagh,
graphene oxide (RGO) Taher,
Hg2+ 0.07 to 80 μg L− 1 0.02 μg L− 1 Heydari,
Ghanei-
Motlagh, &
Gupta, 2016)

39
 13 Ion imprinted polymer (IIP) Electrochemical
with Pb (II) as a template,
methacrylic acid as a
monomer, 8-
hydoxyquinoline as a (Hu, Xiong,
ligand, ethylene glycol Pb2+ 0.05 – 60 μM 0.01 μM Huang, &
dimethacrylate (EGDMA) Lai, 2016)
as a crosslinker, and
azobisisobutyronitrile as
initiator.
14 Carbon ionic liquid paste Electrochemical (Bahrami,
electrode (CILE) Besharati-
impregnated with novel 0.5 nM–10 nM and Seidani,
Hg2+ 0.1 nM
Hg2+ ion imprinted 0.08 μM–2 μM Abbaspour,
polymeric nanobeads (IIP) & Shamsipur,
based on dithizone 2015)
15 Glassy carbon electrode Electrochemical (Behnia,
(GCE) modified with zinc 5 × 10−10 to Asgari, &
Zn (II) 0.5 nM
ion-imprinted polymers 1 × 10−8 M Feizbakhsh,
(GC/IIP) 2015)
458

40
459 3.3.4 Other types of Sensors

460 Presence of heavy metals in water can be detected through several chemical and electrical sensors

461 that include, electrochemical, impedimetric, electronic tongue (e-tongue), electronic nose (e-nose)

462 mediated detection. This section describes some of the prominent detection evidences of several

463 heavy metals in portable water through the mention techniques.

464 Noble metal based electrodes were used by Wei, J.et al (2015) to detect heavy metals like Cr(IV)

465 in water through voltammetric technique. They used electrochemical impidence spectroscopy to

466 detect trace amount of chromium in drinking water. The strategy was such that the crown ethers

467 bind to HCrO4- specifically to form sandwich complexes. This complex formation inhibits the

468 access of redox probes to the Au electrode. This in turn increases the electron transfer resistance

469 that can be measured. The scientist have reported the range of detection as 1 to 100 ppb and the

470 LOD as 0.0014 ppb at pH 5 (Wei, et al., 2015). Similarly, Canhoto, O. F., & Magan, N. (2003)

471 had showed an indirect measurement of heavy metal concentration in water through e-nose using

472 bacterial culture as an assisted signal transducer. They have shown that the presence of 0.5 ppm

473 concentration of heavy metals can change the volatile production patterns by modifying the

474 activity of microorganisms. Different microbial species like Escherichia coli, Enterobacter

475 aerogenes, Pseudomonas aeruginosa was used to detect low concentrations of different heavy

476 metals Cd, As, Pb and Zn using an electronic nose (Canhoto & Magan, 2003). Teodoro, K. B et

477 al. (2019) has reported a modified electronic tongue based heavy metals detection in water where

478 cellulose nanowhiskers (CNW), nanocomposites based on electrospun nanofibers and silver

479 nanoparticles is used as the sensor material. The mentioned materials are combined to form 6

480 different sensing materials that are used to fabricate an impedimetric e-tongue. They have shown

481 that the sensor array can efficiently detect Pb2+ at concentrations as low as of 10 nmol L−1 in

41
482 drinking water (Teodoro, Shimizu, Scagion, & Correa, 2019). Similarly, an automated electronic

483 tongue was developed by Mimendia et al (2010) for the detection of mixture of heavy metals like

484 Pb2+, Cd2+ and Cu2+ in water. They have used the sequential injection technique to get the best

485 output. They have formed a sensor array that contains four Ion Selective Electrode (ISE) sensors.

486 Among the four sensors, two were based on Cd and Cu while the rest were Pb and Zn sensors. Fast

487 Fourier Transform (FFT) and Artificial Neural Networking (ANN) was implemented to get best

488 results from the sensor array (Mimendia, Legin, Merkoçi, & del Valle, 2010). Electronic tongue

489 based redox water quality sensors were explored by Kuhlman, G. M. et al. (2004) for the detection

490 of heavy metals in water. They have used nine planar electrochemical cells along with a

491 conductivity sensor. Detection of heavy metals was performed by anodic stripping voltammetry

492 (ASV). They have reported a linear calibration curve for Pb, Cu, Zn and Mn cations (Kuhlman,

493 Keymeulen, Buehler, & Kounaves, 2004). A novel electronic tongue coupled with stripping

494 voltammetry was used for environmental contamination detection by Men, H.et al (2005). They

495 have used multiple light-addressable potentiometric sensor (MLAPS) along with two groups of

496 electrochemical sensors for the efficient detection of Cr(VI) and Fe(III) ions. Anodic and cathodic

497 stripping voltammetry was used to detect low concentrations of heavy metals in water along with

498 a prototype development of a field portable handheld electronic tongue (Men, et al., 2005).

499 Moreover, Wilson, D. et al. (2012) has reported an automated flow injection potentiometric system

500 with electronic tongue for the efficient detection of heavy metals in water. The electronic tongue

501 was an array of 5-sensors that includes Cu2+ and Ca2+-selective electrodes. With this sensor array

502 real time monitoring of the heavy metals is possible. They used ANN for better output generation

503 form the sensor array as well (Wilson, Del Valle, Alegret, Valderrama, & Florido, 2012).

42
504 Besides these various modern sensor based detection techniques, scientists also explored

505 nanomaterials to detect trace amount of heavy metals in food. Wenqin Wu, et al., has proposed the

506 use of Fe3O4 nanoparticle coupled multiwall carbon nano tubes and its fluorinated versions towards

507 the detection of Cd2+, Pb2+, Cu2+, and Hg2+ in food. They have reported the LODs of the Fe3O4/F-

508 MWCNTs electrochemical sensor were 0.08, 0.02, 0.05 and 0.05 nM for Pb2+, Cu2+, Hg2+, Cd2+

509 respectively (Wenqin Wu, et al., 2019). Similarly, Pungjunun, K. et al. (2020) has mentioned the

510 use of bismuth nanoparticle modified graphene screen printed electrode for the electrochemical

511 detection of Sn(II) and Pb(II) in canned food samples. They used square-wave anodic stripping

512 voltammetry technique in presence of CTAB and oxalic acid to reduce the interferences. Under

513 optimal conditions, both metals showed a good linear range of 10–250 ng mL−1, and their LODs

514 were calculated as 0.26 ng mL−1 and 0.44 ng mL−1 for Sn (II) and Pb(II), respectively (Pungjunun,

515 et al., 2020). A FET based ion selective sensor was developed by Tatavarthi, S. S. et al. (2020) to

516 detect Arsenite (As(III)) in food and water. The developed sensor showed a high sensitivity

517 towards arsenite with a dynamic range of detection of 10−10 M to 10−4 M. They have reported the

518 LOD of the sensor as 10−10 M that is comparable to the conventional detection through ICP-MS

519 (Tatavarthi, Wang, Wang, & Chen, 2020). Similarly, a fluorinated graphene/gold nanocage

520 nanocomposite was developed by Tan, Z.et al. (2020) towards the detection of heavy metals in

521 agricultural food. The scientists used the developed fluorinated graphene/gold nanocage

522 (FGP/AuNC) electrode for the simultaneous detection of heavy metals like Cd2+, Zn2+, Cu2+, Pb2+

523 and Hg2+ through anodic stripping voltammetry in real samples like tea, peanut, ripe bolt etc. They

524 have reported that the results were highly consistent and very much relatable with the conventional

525 detection techniques like ICP-MS or AAS (Tan, Wu, Feng, Wu, & Zhang, 2020). Moreover,

526 Zhang, W. et al (2020) has reported the use of gold nanoparticles modified electrode based smart

43
527 device towards the detection of heavy metals in cow milk, orange juice and apple juice etc.. They

528 have also developed a solid stage microwave digestion device for the proper digestion of the

529 sample. The electrochemical analysis showed good sensitivity towards detection and a stability up

530 to 72 hours (W. Zhang, et al., 2020). Palisoc et al. (2019) has also reported the use of a graphite

531 based electrode extracted from a Zn battery towards the detection of Cd and Pb in trace amounts

532 in herbal food supplements. The electrodes were modified with bismuth nanoparticles and used in

533 anodic stripping voltammetric technique for trace metal detection. The linear range was found to

534 be 5 ppb to 1000 ppb with LODs of 1.06 ppb for Cd2+ and 0.72 ppb for Pb2+ (Palisoc, Vitto, &

535 Natividad, 2019) .

536 Both sensors and biosensors have their own pros and cons. Attributed to the use of bioreceptors,

537 biosensors possess high specificity and affinity. One the other hand, they are expensive and

538 inherently unstable due to the biological origins. The bioreceptors greatly increase the production

539 cost of biosensor devices. Preserving their activity is another big challenge, as their functions are

540 easily affected by the complex immobilization procedures and harsh environmental conditions,

541 resulting in short shelf-lives. Compared to the enzymes and aptamers, the biomimetic ion

542 imprinted polymers could be a good option to address the cost and stability issues. We envision

543 that the high robustness and stability under a wide range of conditions, easy design of recognition

544 sites for analytes, and low production cost would make ion imprinted polymers more popular in

545 future biosensors for heavy metal detection. Another inherent limitation of biosensors is the low

546 multiplexing capability. Most biosensors are dedicated to specific analytes, therefore not

547 transferable between applications. For multi-analyte analysis, parallel biosensors are needed,

548 which significantly increases the technical expenditure. On the contrary, chemical/physical sensors

549 can easily be adapted for multiplex detection, whereas lack of specific recognition elements makes

44
550 them prone to interferences in the complex sample matrix. Therefore, the selection of appropriate

551 sensing methods is highly depending on the water sample types, the operational environments, the

552 affordability, as well as the requirements on sensitivity, selectivity and the throughput.

553 4. Field-portable commercialized instruments

554 This section explicitly gives a brief review of the market available portable instruments which are

555 widely used and distributed. Integration of different units of target recognition, signal generation,

556 signal transduction or amplification, signal reception and signal processing element result in a

557 production-worthy heavy metal ions detection system to replace traditional signal detectors and

558 workstations. Various materials and devices have been explored towards miniaturization of such

559 units (Mehrotra, 2016). Analogue to digital conversions has been applied to demonstrate

560 quantitative analysis of heavy metal ions. The goal of miniaturization has become more real owing

561 to high-end computation like Big Data, cloud computing and neural network with the help of

562 intelligent processors (Dash, Shakyawar, Sharma, & Kaushik, 2019). Introduction of light-

563 emitting diodes (LEDs), complementary metal oxide semiconductor (CMOS) or charge-coupled

564 device (CCD) based camera and smart phones and miniaturized electronic components (two, three

565 or four layer PCB) enable the designing of portable sensor devices towards processing optical or

566 electrochemical signals. This generates a new strategy to replace classical bulky and expensive

567 components by combining the smartphone or camera or imaging system to realize a portable, rapid,

568 and cost-effective quantitative detection. Table 6 lists some market available devices for detection

569 of heavy metals.

570 As shown in the table, majority of the commercial devices are based on either electrochemical

571 detection or optical detection. Both of them are powerful and convenient analytical tools for the

45
572 rapid and on-site detection of heavy metals. However, compared to the laboratory-based

573 instruments, the analytical parameters of these portable devices are inevitably comprised due to

574 the miniaturization. Therefore, the design and development of new sensors and biosensors with

575 improved characteristics are required to overcome these limitations. One promising strategy is to

576 combine the advanced nanomaterials with the sensors and biosensors to enhance their

577 performance. For optical sensors and biosensors, colorimetric and fluorescence assays are the most

578 popular signal transduction methods. New types of nanomaterial-based optical labels, such as

579 quantum dots, upconversion nanoparticles provide lower background and sharper emission

580 bandwidths, thereby leading to higher sensitivity. For electrochemical sensors and biosensors, the

581 efficiency is largely dependent on the appropriate selection of the transducer surface. Modification

582 of electrodes with different nanomaterials such as carbon nanostructures or metal/polymer

583 nanomaterials can offer higher conductivity and catalytic activity to accelerate signal transduction,

584 resulting in increased signals. We believe more excellent platforms that harness the synergistic

585 effects of nanomaterials and sensors/biosensors will appear on market for heavy metal detection.

586

46
587 Table 6: Market available devices for detection of heavy metals
S.N. Handheld Targeted Principle of Detection Image Specifications Reference
Device Heavy Metals
1. uMED Cadmium, Sqare wave anodic LOD = 4µg/L (Nemiroski,
Zinc, Lead stripping voltammetry • Rapid Detection and et al., 2014)
screening
• Best for analysis in
resource limited
condition.

2. ANDalyze Lead, Copper, Fluorescence based LOD = 2 µg/L(Pb), 0.6 (ANDalyze)

Zinc, Cadmium sensing µg/L(Cu), 1 µg/L(Zn),
0.1 µg/L(Cd)
• User friendly
detection procedure
without any user
training
• Rapid detection
(Less than 2
minutes)
• Highly sensitive and
selective
• Computer based
result monitoring
• re-sampling time is
minute
• No harmful reagents,
environmentally
friendly.

47
3. DEP-Chip Cadmium, Differential pulse LOD = 2.6 µg/L (Cd), (Biyani, et
Lead, Arsenic, voltammetry 4.0 µg/L (Pb), 5.0 µg/L al., 2017)
Copper, Zinc (As), 15.5 µg/L (Cu),
14.4 µg/L (Zn).

• Disposable electrode
printed (DEP)-On-
Go

4. AppliTrace Cadmium, Anodic stripping LOD = 1µg/L (AppliTrace

Lead, Copper, voltammetry • Hot acid Digestion. )
Arsenic, Zinc, (decompose organic
Iron matters to reduce
noise)
• Pre concentration
methods for better
detection.

48
 5. Portable Cadmium in Anodic stripping • Cost: Low cost than (MRC)
heavy rice and voltammetry atomic absorption
metal ion heavy metals spectrophotometry.
detector (as zinc, • With glassy carbon
INE-SJB- cadmium, electrode system,
801 arsenic, this is accurate, low
mercury, etc.) detection limit,
analysis in suitable for precise
drinking measurement.
water. • With screen-printed
electrode test
system, plug and
play, suitable for
rapid detection on
the spot
588

589

49
590 5. Pros and cons of current devices

591 Over the recent years, advances in system integration and automation have accompanied with the

592 fabrication of many analytical instruments for the detection of heavy metal ions. Most of the

593 reported methods have presented the privileges of high accuracy and design simplicity,

594 nevertheless, there are some deficiencies regarding the development of an ideal sensing device for

595 heavy metal detection.

596 Reproducibility and signal stability is still a big challenge in the development of sensors when

597 operating within low concentrations of analytes. Although advances in nanotechnology and

598 integration with sensors/biosensors have enabled fabrication of highly sensitive platforms, yet to

599 overcome the issue due to the difficulties in controlling the size distribution and homogeneity of

600 nanostructures in large scales. Another challenge would be the multiplexing and selectivity of

601 current devices. The commercialized systems mainly lack the bio-recognition elements to make

602 them less selective and hamper their multiple quantification ability. Onsite monitoring of water

603 pollutants is also another issue, as there is a dramatic variation between the water quality and pH

604 in different sampling areas to make it difficult to use the same device in e.g. Asia and Europe and

605 expect to observe similar results. In addition, there is still a high demand for the fabrication of an

606 affordable and fully-automated field-portable device for the real-time monitoring of various heavy

607 metal ions on a single platform.

608 6. Conclusion

609 This endeavor states about various conventional development along with recent trends like sensor

610 based development towards field portability. The conventional systems will always be sensitive

611 approach. In parallel to the conventional analysis, field-portable sensors are very much promising

50
612 wherein rapid screening is concern. Previously, the column sensitivity in conventional systems

613 was the concern for the scientists. Thus, researchers developed new column materials which could

614 be able to reach at the limits set by various regulatory authorities. In later stage, it has been found

615 that these conventional detection systems are lagging for rapid screening and field-portability.

616 Sensors or biosensors are integrated with receptors and decision support system (DSS) which

617 enable the features like pace and portability. These sensory systems come with receptors,

618 transducers and DSS along with digital display as a package. New age receptors like aptamers

619 (synthetic receptors) and ion-imprinted receptors have been exhibited the forte in the

620 transformation from classical receptors like enzymes, antibodies etc. to smart receptors. A

621 significant numbers of studies have been based on developing stable receptors, immobilization of

622 receptors and resulted in a solid background and experience in this field. Earlier, receptors were

623 mainly used for the detection of trace heavy metals in various types of water bodies, because the

624 principal condition for conducting a signal (either optical or electrochemical) was the presence of

625 a label marker. Thus, it was difficult to extract heavy metal ions from soil, plants, or other solid

626 objects. The recent progress on the efficient extraction of heavy metal ions from solid media allows

627 working on fruits, vegetables and soils etc. However, numbers of other ions, orientation of

628 receptors are the areas where a considerable attention should be waged to reduce interference and

629 noise. In view of work done towards development of field-portable sensory for heavy metal

630 detection, optical and electrochemical based sensors are evolving as cheaper and simpler approach

631 than some other methods. However, there are need in terms of increased reproducibility and anti-

632 interference ability among these sensor devices. Therefore, future research on optical and

633 electrochemical fields may build upon these aspects.

51
634 Declaration of competing interest

635 The authors declare that they have no known competing financial interests or personal

636 relationships that could have appeared to influence the work reported in this paper.

637 Acknowledgments

638 This endeavor has been performed in the Indo-Danish Research and Innovation Cooperation in the

639 Area of Water. Authors acknowledge the joint funding by Department of Biotechnology (DBT),

640 Government of India [Grant ID: BT/IN/DENMARK/62/NB/2018-19 (PFMS), dated 23/03/2019]

641 and Innovation Fund Denmark [8127-00021B]. The authors also thankful to Ministry of

642 Electronics and Information Technology (MeitY), Government of India for their continuous

643 support.

644

52
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