INTRODUCTION:

Pathogenic bacteria and fungi cause severe human health cases, especially in several infectious diseases. The World Health Organization (WHO) states that resistance to antimicrobials and antibiotics is a significant health problem. Antibiotics that are used inappropriately and excessively can lead to bacterial resistance^1,2. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are two of the most common bacteria that exhibit antibiotic resistance effects, such as causing other severe intestinal, skin, and soft tissue infections, including pneumonia, endocarditis, and septicaemia³.

Centers for Disease Control reports that more than 2.8 million bacterial antibiotic resistance occurs yearly, resulting in approximately 35,000 people dying in the United States⁴.

This condition requires media as medical diagnostic support that is more sensitive, fast, and easy to use in detecting bacteria in disease to minimize the risk of irrational use of antibiotics for the patient's condition and reduce mortality due to resistance^5–7.

A previous study designed the detection of bacteria E. coli colorimetrically using cysteine-modified gold nanoparticles (CAuNPs) and synthesizing a nanosensor system based on a combination of gold nanoparticles (AuNPs) with smart pH-responsive acrylic acid polymer. Smart polymers are biocompatible, non-thrombogenic, firm, elastic, flexible, and easy to shape and color, resulting in the increased use of intelligent polymers in biomedical applications in recent decades^8,9.

Most responsive systems are designed for controlled drug delivery and overcoming the drawbacks of systemic drug delivery, while new materials for diagnostics and tissue engineering are developed¹⁰. Then, a review shows that using smart polymers can increase the sensitivity and selectivity of sensor devices¹¹. However, previous study review available sensors, not specifically for colorimetric sensors to detect pathogenic bacteria. Based on this, the literature review aims to determine the sensitivity and selectivity of responsive polymers as colorimetric sensors against pathogenic bacteria.

MATERIALS AND METHODS:

The method used in preparing this narrative review is conducting a literature search through the Pubmed database. The search was carried out using keywords (sensitive polymers OR responsive polymers) AND (colorimetric detection OR colorimetry) AND (bacteria OR pathogen). The literature analyzed all types of research that used responsive polymers as colorimetric sensors against pathogenic bacteria and satisfied the inclusion and exclusion criteria. The inclusion criteria used are primary literature with publication years 2010-2020 which discusses responsive polymers in colorimetric sensors against pathogenic bacteria. The exclusion criteria used are articles that examine responsive polymers in colorimetric sensors against pathogenic bacteria that do not have full text and articles that use colorimetric sensors to detect viruses or chemicals.

RESULT AND DISCUSSION:

Types of responsive polymers:

Responsive polymers have the characteristics to respond to changes caused by small environmental changes. These polymers have rapid and reversible microstructure changes triggered by small environmental stimuli ¹²,so using responsive polymers can provide a better sensor response. Responsive polymers are grouped into three categories: thermoresponsive polymers (responsive to temperature), polymers responsive to pH, and polymers responsive to other stimuli.

Table 1: Categories of polymers responsive to stimuli

Responsive Polymer Category	Polymer Type	Stimulation
Temperature responsive polymers	PNIPAm	25°C
	PDMS	20-25°C
	PDMA	25°C
pH-responsive polymers	PMMA	Not known
	PEI	pH 5.5 – 6
	BPEI	pH 7
	CMCS	Not known
Responsive polymers and other stimuli	3-Phenylthiophene	Lipopolysaccharide
	PGA	Ionic interaction
	PDAs	Chemical molecule cadaverine

Thermoresponsive polymer:

Thermoresponsive polymer will show a response to changes when there is a stimulus in the form of temperature. The temperature-responsive polymers consisted of poly-N-isopropyl acrylamide (PNIPAm), polydimethylsiloxane (PDMS), and poly(-dimethylamino) ethyl methacrylate (PDMA) (Figure 1). The three types of polymers are responsive at 25°C or room temperature. PNIPAm has an LCST value of 30°C and is used in the synthesis of gold nanoparticles (AuNPs), resulting in a fast and efficient color change response^13,14. The colorimetric method based on AuNPs with PNIPAm conjugated with acrylic acid (PNIPAm-co-AAC) successfully responded to the presence of streptavidin protein, indicating bacteria Streptomyces avidin¹⁵.

PDMS is a thermoresponsive polymer with many advantages, including high flexibility, optical transparency, low cost, and biocompatibility. PDMS is widely used for various applications ranging from soft lithography to microfluidics but not much use of PDMS for sensing applications in liquids¹⁶.

PDMA is a thermoresponsive polymer with a value of Lower Critical Solution Temperature (LCST) 40-50°C¹⁴. LCST is the lowest critical temperature point at which the mixture's components are soluble for all compositions. PDMA is also a weak polyelectrolyte; therefore, the effect of solution pH can affect the critical phase transition temperature of PDMA. It is known that pH affects the behavior of the LCST type of PDMA; when under LCST, the polymer generally forms hydrogen bonds with the surrounding water molecules. As the temperature approaches the LCST, the hydrogen bonding interactions between the polymer chains and the water molecules are partially disrupted. The polymer enters a conformational transition from the extended coil to the spherical coil. At pH 8 (25°C), PDMA shows a broader conformation and more binding points, thus increasing the sensor's sensitivity. Because of that, PDMA combined with PEG is used as an ingredient in manufacturing sensors to detect bacteria E. coli and Staphylococcus aureus¹⁷.

Figure 1: Chemical structure of PNIPAm (a), PDMS (b), and PDMA (c)

pH-responsive polymers:

pH-responsive polymers will show a response to changes in certain pH conditions^18,19. The pH-responsive polymers consisted of PMMA, PEI, branched PEI, and CMCS (Figure 2). Previous research proved that polymethyl methacrylate (PMMA), a pH-responsive polymer combined with temperature-responsive polymer PDMS, is used in colorimetric sensors capable of detecting Acinetobacter baumannii (AB). The PMMA is combined with PDMS, which includes polymers thermoresponsive, so its detection ability is more influenced by temperature. PMMA has a UCST value of 25-55°C, which causes the insoluble polymer to become soluble gradually between these temperatures²⁰.

CMCS is combined with an aptamer which also plays a role in detecting bacteria so that the binding of bacteria influences the detection response to the aptamer. While CMCS here plays a role in making the nanocomposite (sensor system) positively charged (because of the amino group of CMCS) so that it can cross cell membranes to detect bacteria S. typhi directly without extracting the DNA. Carboxymethyl chitosan (CMCS) is also used in synthesizing AuNPs as a reducing and stabilizing agent because of its oxygen-rich structure in the hydroxyl and ether groups, so it binds strongly to metals through electrostatic interactions of nanoparticles. AuNPs-based colorimetric sensor method with CMCS can respond to the presence of bacteria S. typhi²¹.

PMMA combined with poly butyl acrylate (PBA) can respond to the presence of S. aureus. The sensor system uses polyvinylpyrrolidone (PVP), a water-soluble, non-ionic, non-toxic surfactant polymer. It is a stabilizer or capping agent to protect nanoparticles from coagulation or precipitation in the synthesis of AuNPs. PVP-coated AuNPs were significantly more stable, likely due to the steric repulsion exerted by the large, uncharged polymer²².

PEI is responsive at pH 5.5–6, with a detection time of 6 minutes. Then the branched PEI was responsive at pH 7 and could detect E. coli. BPEI is a water-soluble and amine-rich cationic polymer. Tertiary amines from BPEI play a central role in pH-responsive behavior, thus having wide applications in biology and metal ion detection. PEI is used in the synthesis of AuNPs as a stabilizing and reducing agent²³.

Figure 2. Chemical structure of PMMA (a), PEI (b), BPEI (c), and CMCS (d).

Polymers responsive to other stimuli

Several polymers responsive to temperature and pH have been used as sensors for pathogen bacteria (Table 2). In addition, some polymers are responsive to other stimuli through specific molecules. Three types of polymers are responsive to other stimuli, namely 3-Phenylthiophene, PEG, and PDA. 3-Phenylthiophene is a conjugated, water-soluble polymer with excellent optoelectronic properties such as adjustable fluorescence property, Fluorescent Resonance Energy Transfer (FRET), and adjustable electrical conductivity. Phenylthiophene is a polymer responsive to stimuli, so its sensitivity is high. The fluorescence properties of polythiophene are appropriate for sensing and developing biological sensors with environmentally friendly processes²⁴. This polymer can recognize the presence of stimulation in the form of lipopolysaccharides in Gram-negative bacteria such as Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa.

Polyethylene glycol (PEG) and poly(-dimethylamino) ethyl methacrylate (PDMA) can respond to bacteria E. coli. This response is because PEG is a polymer responsive to stimuli and has high structural flexibility, biocompatibility, amphiphilicity, no steric hindrance, and high solubility. PEG plays a role in ionic exchange reactions in compiling the sensor system.

Polydiacetylenes (PDA) are conjugated polymers with unique optical properties with an LCST value of 55⁰C²⁵. This polymer will change color (usually blue to red) when it recognizes the chemical molecule cadaverine produced by lysine decarboxylase in defense against Salmonella choleraesuis. A color change indicates the presence of Salmonella choleraesuis detected by the sensor device^26,27.

Figure 3: Chemical structure of 3-phenylthiophene (a), PEG (b), and PDA (c)

Table 2: Use of responsive polymers in colorimetric sensors

Polymer Type	Colorimetric Method	LOD	LCST/UCST	Bacteria Type	Superiority	Ref.
3-phenylthiophene	CPT1 soluble in water based 3-Phenylthiophene	10⁸ CFU/mL	-	E. coli, K. pneumoniae, P. aeruginosa	Polymers have the properties the optoelectronic very good, and selective on Gram-Negative	²⁸
PEI	Colorimetric based bioactive paper	< 10 μL = 0,01 mL	-	G. vaginalis, M. hominis, Mobiluncus species, which are gram rods negative anaerobic on woman with BV	Do not need sample preparation steps, sensor system can stored for a minimum of 12 months, easy used, and selective	²⁹
PNIPAm-co-AAC	Gold nanoparticles - PAH-biotin	2,0 x 10⁻⁸ mol	LCST 32⁰C	S. avidinii	Stable, biocompatible and selective	¹⁵
PDA	Colorimetric system vesicle based 10,12-pentacosadyinoic acid (PCDA) / Sphingomyelin (SPH) / Cholesterol (CHO) / Lysine	1 - 100 CFU/mL	LCST 55⁰C	S. choleraesuis	There is SPH/CHO able to lower activation barrier and improve response colorimetric and selective	²⁷
PDMS and PMMA	Microfluidic chip	450 CFU/ reaksi	UCST PMMA (25-55⁰C)	Acinetobacter baumannii (AB)	Able to detect in complex sample on nitrocellulose membrane, easy to use, and selective	³⁰
BPEI	Plasmonic enhanced lateral flow sensor (PLFS) with label biotinylated liposomes-AuNPs	100 CFU/mL	-	E. coli O157: H7	Stable, biocompatible and selective	³¹
CMCS	CMCS-Aptamer-AuNPs	16 CFU/mL	-	S. typh	Stable, biocompatible and selective	²¹
PEG and PDMA	PD-Nanocomposite bcd-MMT / Fe3O4eCsWO3	10¹ - 10⁷CFU/mL	LCST PEG (99-176⁰C) PDMA (40-50⁰C)	E. coli, S. aureus	Polymer with structural flexibility and high solubility, as well as the sensor system can recycle	¹⁷
PMMA and PBA	Gold nanoparticles	10⁶ CFU/mL	UCST PMMA (25-55⁰C)	S. aureus	Unique optical properties, stable, biocompatible and selective	³²

Responsive polymer-based sensor colorimetric method:

Gold nanoparticle colorimetric method:

Based on the analysis of nine articles, several colorimetric methods were obtained, which were used as sensors (Table 2). Four articles used the colorimetric method of gold nanoparticles (AuNPs) and responsive polymers. The results showed that colorimetric-based AuNPs modified with responsive polymers gave better sensor responses than single AuNPs. Gold and silver nanoparticles have excellent physicochemical properties, high surface area, unique optical properties, stability, small-size properties, and non-cytotoxicity. They are proven the safest, so they are widely used for drug applications with various methods and fields, including drug delivery, sensing, and detection³³.

The main advantages of this method lie in the unique optical properties and the apparent color change depending on the environment around the nanoparticles^34,35. AuNPs-based colorimetric assays are promising compared to other sensing methods because the entire test proceeds from the target and probe without any washing steps. The naked eye can directly monitor the color change without sophisticated instruments. Therefore, this approach dramatically simplifies operating procedures, shortens detection time, and significantly reduces testing costs. In addition, the colorimetric test is easily adaptable to -based smartphones, which is a potentially powerful platform for detecting, transducing, and analyzing online sensing information^29,36.

Several studies have used PEI, PNIPAm conjugated with AAc, CMCS, and PMMA with PBA, which can detect pathogenic bacteria in colorimetric sensors based on gold nanoparticles. These polymers will affect the aggregation of gold nanoparticles to increase the sensor's sensitivity. Responsive polymers have a mechanism for detecting bacteria. PEI and branched PEI have the exact detection mechanism, namely recognizing E. coli through increased sialidase activity, indicating the growth of E. coli during inflammation²⁹.

The detection mechanism in PNIPAm is through the interaction between poly(allylamine hydrochloride) (PAH) and streptavidin protein; when an excess amount of streptavidin is added to a biotin-modified PAH, a streptavidin-biotin-PAH complex will be formed. Then the complex was removed from the solution using biotin-modified magnetic particles, leaving the PAH free and unbound. PAH-free added to etalon-based pNIPAm-co-AAc microgel. As a result, the microgel layer collapses, bringing the etalon mirrors closer to each other, resulting in a blue shift in the peaks of the etalon reflections.

CMCS-Apt-AuNP has a detection mechanism through aptamer interaction with bacteria S. typhi. When S. typhi is inserted into the CMCS-Apt-AuNP composite, it binds specifically to the aptamer, which changes the conformation of the composite so that the AuNPs fall off the composite and are in a free state in solution. When sodium chloride is added, free AuNP will agglomerate; not only will the color of the solution change from red to blue, but the absorbance will also change significantly.

PMMA and PBA have a detection mechanism through changes in pH. S. aureus can ferment glucose which causes the solution to become acidic and decrease in pH from 8 to 4.5. The change in pH was responded to by PMMA and PBA, which was marked by a change in color to red.

Colorimetric method copoly-thiophenes:

The mole ratio is varied in the water-soluble co-poly-thiophenes (CPT1) based on 3-phenylthiophene. For copolymerization, monomers 4 and 2 with different mole ratios (1/1, 1/2.5, and 2.5/1) were used to produce the appropriate copolymerizations (CPT1-A, CPT1-B, and CPT1-C, respectively). Polymerization of monomers 2 and 4 yields the corresponding homo-polythiophene PT1 and PT2. The results show that CPT1-C with a mole ratio of 2.5/1 is very sensitive and selective in detecting Gram-Negative bacteria because it quickly gives a signal response and visually more apparent color changes in 3 samples of Gram-Negative bacteria (Table 2) compared to 2 samples of Gram-Positive bacteria (S. epidermidis and S. aureus)²⁸. The detection mechanism of the sensor system is to recognize Gram-Negative bacteria that contain lipopolysaccharide (LPS) by a 3-Phenylthiophene polymer. This method lacks sensitivity because it shows a general detection response in Gram-negative bacteria, not specific to one type of bacteria.

Bioactive paper colorimetric method:

Bioactive paper-based colorimetric for neuraminidase detection was prepared by introducing PEI microcapsules containing BCIN and NBT into paper pulp. The mechanism of bioactive paper in detection is through BCIN, which is hydrolyzed in the presence of sialidase at pH 5.5-6 to produce indoxyl, and then the indoxyl isomer is oxidized to blue indigo dye at a higher pH (pH> 9); indoxyl (hydrolyzed monomer) was oxidized in the presence of NBT at a higher pH (pH > 9) to form a dark purple precipitate. This paper strip has several advantages, such as increased visibility of color reactions. Due to the presence of PEI microcapsules, it can be stored for a minimum of 12 months, requires no sample preparation step, small sample quantities (< 10 µL) can be directly added to small pieces of bioactive paper, and the response time of BV detection is only 6 minutes, making the test easier. Compared to other methods, it can be used by women directly without needing experts²⁹.

Vesicle colorimetric method PCDA/SPH/CHO/lysine:

PCDA/SPH/CHO/Lysine-based colorimetric vesicles gave a more explicit response when compared to other vesicles, such as PCDA/DMPC/Lysine. This response is due to the presence of SP/CHO, which can reduce activation barriers and increase the colorimetric response of bacteria and color changes visible to the naked eye due to the presence of lysine. Lysine will detect the chemical molecule cadaverine produced by lysine decarboxylase in defense of Salmonella choleraesuis so that the interaction between bacteria and lysine causes a spectrophotometric transition²⁷. The advantage of this method is that it has better sensitivity than other methods because it can respond only with a detection limit of 1 CFU/mL.

Microfluidic chip colorimetric method:

The microfluidic chip-based colorimetric consists of a cover layer, a PDMS top layer, a magnetic composite membrane layer, a valve layer, and a sliding glass substrate. In this sensor system, responsive polymers are used, and aptamers are used to capture AB in complex samples on nitrocellulose membranes. A simple colorimetric test is used to estimate the number of bacteria. This aptamer-based microfluidic system is easy to use and has a sensitivity for on-site diagnostics³⁰. However, this method requires several layers in compiling a sensor system, while the other colorimetric methods are more straightforward.

Colorimetric method of PD-bcd-MMT/Fe. nanocomposite3O4eCsWO3:

PD-bcd-MMT/Fe. nanocomposite₃O₄eCsWO₃ is a fluorescent-based biosensor with antibacterial activity prepared by point insertion of an ALP-sensitive polymer (PD) containing -cyclodextrin (β-CD) into montmorillonite (MMT) as a loading matrix via an ionic exchange reaction, followed by immobilization of magnetic iron oxide (Fe)₃O₄) and cesium tungsten oxide (CsWO₃) which is responsive to NIR. The detection mechanism of the nanocomposite is the suppression by bacterial ALP (0–1000 U/L) due to the hydrolysis of p-nitrophenyl phosphate (NPP) to p-nitrophenol (NP) at the hydrophobic site of -CD, which then the detection response is indicated by strong fluorescence intensity. The nanocomposite sensor system can detect E. coli and S. aureus and has high antibacterial activity against bacteria by producing photothermal. After four cycles, the nanocomposite still showed a stable photothermal effect, hence the reusable material for detection (recyclable) and bacterial killing simultaneously, which is simple, fast, and effective¹⁷. However, compared to the AuNPs-based colorimetric method or other methods, the response of the nanocomposite system is in the form of fluorescence quenching, requiring an instrument to observe it. In contrast, other methods can be observed from the color change without needing an instrument.

Responsive polymer-based sensor sensitivity and selectivity:

The sensor's sensitivity will indicate its sensitivity to the measured quantity. In general, the sensitivity to bacteria can be observed based on the sensor response to the concentration of bacteria in CFU/mL (Table 2). The sensitivity of the polymer is indicated by the LOD or detection limit. The selectivity is seen from the sensor's ability to distinguish specific bacteria. There are differences in sensor responses between Gram-Negative and Gram-Positive bacteria (Table 3 and Table 4) of the nine responsive polymers having sensitivity with a detection limit range of 1-10⁸ CFU/mL. For the lowest LOD value of 1 CFU/mL shown by PDA, PDA has high sensitivity and selectivity to Salmonella choleraesuis^27,37.

PEG and PDMA in Polymer Dot (PD) with a 10 CFU/mL detection limit successfully detected E. coli characterized by fluorescence quenching. Still, the polymer is not selective to E. coli only because it can detect the presence of S. aureus also³¹. CMCS polymer with a detection limit of 16 CFU/mL can detect contaminated samples of S. typhi with reasonable specificity and accuracy and, characterized by a change in the color of the solution from white to green²¹, and a branched PEI with a detection limit of 100 CFU/mL sensitive to bacteria E. coli O157: H7 in a buffer in liquid food systems.

Responsive polymers with high LOD values include PMMA, PBA, and 3-Phenylthiophene. PMMA and PBA can detect S. aureus with a detection limit of 10⁶ CFU/mL, indicated by a color change from red to purple³². Meanwhile, 3-Phenylthiophene has high sensitivity and selectivity to bacteria E. coli, K. pneumonia, and P. aeruginosa (Gram-Negative) with a detection limit of 10⁸ CFU/mL as indicated by a visual color change from yellow to orange and the fluorescence color changing from yellow to pink²⁸.

A total of four responsive polymers showed sensitivity that was not indicated by CFU/mL units, such as PDMS, PMMA, PEI, and PNIPAm-co-AAc. PDMS and PMMA can detect Acinetobacter baumannii (AB) with a detection limit of 450 CFU/reaction, which is characterized by a change in color from white to green and has selectivity towards AB³⁰. PEI with a detection limit of 0.01 mL could recognize the presence of Gram-Negative bacteria Gardnerella vaginalis, Mycoplasma hominis, and species Mobiluncus which are anaerobic bacteria in women with Bacteria Vaginosis (BV). The sensor response is indicated by a color change from white to dark purple within 6 minutes^29,31. Meanwhile, PNIPAm-co-AAc, with a detection limit of 2.0x10⁸ mole, can detect Gram-positive bacteria Streptomyces avidinii marked in blue in the solution^15,38.

Table 3: Response of polymer detection responsive to Gram-negative bacteria

Responsive Polymers	Color Transition	Bacteria	Type Molecules	Target Molecule	References
3-phenylthiophene	Visually (yellow to orange) and fluorescence (yellow turn pink)	E. coli, K. pneumoniae, P. aeruginosa	polymer 3-phenylthiophene	Lipopolysaccharide (LPS)	28
PEG and PDMA	Fluorescence quenching	E. coli	β -cyclodextrin (β-CD)	Bacterial ALP (0 –1000 U/L)	17
PEI	White to dark purple	G. vaginalis, M. hominis, species Mobiluncus BV	BCIN and NBT	Sialidase	29
PDA	Blue turns red	S. choleraesuis	Lysine	Cadaverine	27
BPEI	Not known	E. coli O157: H7	Liposomes	Sialidase	31
PDMS and PMMA	White turns green	A.baumannii	Aptamer	DNA from AB	30
CMCS	White turns green	S. typhimurium	Aptamer	DNA from S. typh	21

Table 4: Response of polymer detection responsive to Gram-positive bacteria

Responsive Polymers	Color Transition	Bacteria	Type Molecules	Target Molecule	References
PNIPAm-co-AAC	Blue color in solution	S. avidinii	PAH	Streptavidin	15
PMMA and PBA	Red to purple	S. aureus	PMMA	Fermentation results glucose	32
PEG and PDMA	Fluorescence quenching	S. aureus	β -cyclodextrin (β-CD)	Bacterial ALP (0 – 1000 U/L)	17

CONCLUSION:

Several responsive polymers have shown sensitivity and selectivity as colorimetric sensors against pathogenic bacteria. The results showed that the sensitivity of the responsive polymer was greater in Gram-negative bacteria than in Gram-positive. Still, not all types of responsive polymers had selectivity in detecting bacteria. Various responsive polymer-based colorimetric sensor methods have been used, and the majority utilize gold nanoparticles with responsive polymers to construct the sensor system. The conclusions of this narrative review show that the responsive polymer has a sensitivity with a LOD range of 1-10⁸CFU/mL and high selectivity in colorimetric sensors against pathogenic bacteria. The detection method using responsive polymers is a fast, easy, and sensitive method of choice for detecting the presence of bacteria, so it is expected to facilitate the diagnosis of bacterial diseases and reduce the number of bacterial resistances to antibiotics.

CONFLICT OF INTEREST:

The authors declared that there was no conflict of interest.

ACKNOWLEDGMENTS:

The authors would like to thank the Indonesian Government's Ministry of Technology and Higher Education (RISTEKDIKTI) for sponsoring the research (Grant No. 133.4/A.3-III/LPPM/IV/2020).

REFERENCES:

1. Aljanaby AAJ., Aljanaby IAJ. Profile of Antimicrobial Resistance of Aerobic Pathogenic Bacteria isolated from Different Clinical Infections in Al-Kufa Central Hospital –Iraq During period from 2015 to 2017. Res J Pharm Technol. 2017; 10: 3264–70. https://doi.org/10.5958/0974-360X.2017.00579.0.

2. Khushboo K., Saloni B., Singh RK. A Briefing of a Global Crisis: Antibiotic Resistance. Asian Journal of Research in Pharmaceutical Sciences. 2020; 10: 264–72. https://doi.org/10.5958/2231-5659.2020.00047.8.

3. Sreeja MK., Gowrishankar NL., Adisha S., et al. Antibiotic resistance-reasons and the most common resistant pathogens – A review. Res J Pharm Technol. 2017; 10: 1886–90. https://doi.org/10.5958/0974-360X.2017.00331.6.

4. Centers for Disease Control U. Antibiotic Resistance Threats in the United States, 2019 n.d. https://doi.org/10.15620/cdc:82532.

5. Shukla I., Suneetha V. Biosensors: Growth and Market Scenario. Res J Pharm Technol. 2017; 10: 3573–9. https://doi.org/10.5958/0974-360X.2017.00647.3.

6. Rakesh P., Pramod P., Sujit P. Biosensors: Current tool for Medication and Diagnosis. Asian Journal of Pharmaceutical Research. 2019; 9: 27–34. https://doi.org/10.5958/2231-5691.2019.00006.6.

7. Patil LB., Patil SS., Nitalikar MM., et al. A Review on-Novel Approaches in Nanorobotics. Asian Journal of Pharmaceutical Research. 2016; 6: 217–24. https://doi.org/10.5958/2231-5691.2016.00030.7.

8. Raj V., Vijayan AN., Joseph K. Cysteine capped gold nanoparticles for naked eye detection of E. coli bacteria in UTI patients. Sens Biosensing Res. 2015; 5: 33–6. https://doi.org/10.1016/j.sbsr.2015.05.004.

9. Wikantyasning ER., Mutmainnah M., Cholisoh Z., et al. Preparation of hydrogel nanocomposite containing gold nanoparticles with unique swelling/deswelling properties. Rasayan Journal of Chemistry. 2019; 12: 1857–63. https://doi.org/10.31788/RJC.2019.1245209.

10. Gupta NP., Damodharan N. pH - responsive polymers and its application in drug delivery system and pharmaceutical field. Res J Pharm Technol. 2019;12:944–58. https://doi.org/10.5958/0974-360X.2019.00159.8.

11. Reglero Ruiz J., Sanjuán A., Vallejos S., et al. Smart Polymers in Micro and Nano Sensory Devices. Chemosensors. 2018; 6: 12. https://doi.org/10.3390/chemosensors6020012.

12. Pattanashetti NA., Heggannavar GB., Kariduraganavar MY. Smart Biopolymers and their Biomedical Applications. Procedia Manuf. 2017; 12:263–79. https://doi.org/10.1016/j.promfg.2017.08.030.

13. Choe A., Yeom J., Shanker R., et al. Stretchable and wearable colorimetric patches based on thermoresponsive plasmonic microgels embedded in a hydrogel film. NPG Asia Mater 2018;10:912–22. https://doi.org/10.1038/s41427-018-0086-6.

14. Xu J., Luo S., Shi W., et al. Two-stage collapse of unimolecular micelles with double thermoresponsive coronas. Langmuir. 2006; 22: 989–97. https://doi.org/10.1021/la0522707.

15. Islam MR., Serpe MJ. Label-free detection of low protein concentration in solution using a novel colorimetric assay. Biosens Bioelectron. 2013; 49: 133–8. https://doi.org/10.1016/j.bios.2013.05.011.

16. Tang N., Mu L., Qu H., et al. Smartphone-Enabled Colorimetric Trinitrotoluene Detection Using Amine-Trapped Polydimethylsiloxane Membranes. ACS Appl Mater Interfaces. 2017; 9: 14445–52. https://doi.org/10.1021/acsami.7b03314.

17. Robby AI., Park SY. Recyclable metal nanoparticle-immobilized polymer dot on montmorillonite for alkaline phosphatase-based colorimetric sensor with photothermal ablation of Bacteria. Anal Chim Acta 2019;1082:152–64. https://doi.org/10.1016/j.aca.2019.07.053.

18. Gupta NP., Damodharan N. pH - Responsive Polymers and its Application in Drug Delivery System and Pharmaceutical Field. Res J Pharm Technol. 2019;12:944–58. https://doi.org/10.5958/0974-360X.2019.00159.8.

19. Mutalabisin MF., Chatterjee B., Jaffri JM. pH Responsive Polymers in Drug Delivery. Res J Pharm Technol. 2018;11:5115–22. https://doi.org/10.5958/0974-360X.2018.00934.4.

20. Pietsch C., Hoogenboom R., Schubert US. PMMA based soluble polymeric temperature sensors based on UCST transition and solvatochromic dyes. Polym Chem. 2010;1:1005–8. https://doi.org/10.1039/c0py00162g.

21. Yi J., Wu P., Li G., et al. A composite prepared from carboxymethyl chitosan and aptamer-modified gold nanoparticles for the colorimetric determination of Salmonella typhimurium. Microchimica Acta. 2019;186. https://doi.org/10.1007/s00604-019-3827-5.

22. Ye Y., Lv M., Zhang X., et al. Colorimetric determination of copper(ii) ions using gold nanoparticles as a probe. RSC Adv. 2015;5:102311–7. https://doi.org/10.1039/c5ra20381c.

23. Qu F., Li NB., Luo HQ. Highly sensitive fluorescent and colorimetric pH sensor based on polyethylenimine-capped silver nanoclusters. Langmuir. 2013;29:1199–205. https://doi.org/10.1021/la304558r.

24. Das S., Chatterjee DP., Ghosh R., et al. Water soluble polythiophenes: Preparation and applications. RSC Adv. 2015:20160–77. https://doi.org/10.1039/c4ra16496b.

25. Cao Y., Wang Z., Zhang S., et al. Synergetic regulation of CO2 and light for controllable inversion of Pickering emulsions. Mater Chem Front. 2017;1:2136–42. https://doi.org/10.1039/c7qm00275k.

26. Park DH., Hong J., Park IS., et al. A Colorimetric hydrocarbon sensor employing a swelling-induced mechanochromic polydiacetylene. Adv Funct Mater. 2014; 24: 5186–93. https://doi.org/10.1002/adfm.201400779.

27. De Oliveira T V., Soares NDFF., De Andrade NJ., et al. Application of PCDA/SPH/CHO/Lysine vesicles to detect pathogenic bacteria in chicken. Food Chem. 2015;172:428–32. https://doi.org/10.1016/j.foodchem.2014.09.055.

28. Lan M., Wu J., Liu W., et al. Copolythiophene-derived colorimetric and fluorometric sensor for visually supersensitive determination of lipopolysaccharide. J Am Chem Soc. 2012; 134: 6685–94. https://doi.org/10.1021/ja211570a.

29. Zhang Y., Rochefort D. Fast and effective paper based sensor for self-diagnosis of bacterial vaginosis. Anal Chim Acta. 2013; 800: 87–94. https://doi.org/10.1016/j.aca.2013.09.032.

30. Wu JH., Wang CH., Ma YD., et al. A nitrocellulose membrane-based integrated microfluidic system for bacterial detection utilizing magnetic-composite membrane microdevices and bacteria-specific aptamers. Lab Chip. 2018; 18:1633–40. https://doi.org/10.1039/c8lc00251g.

31. Ren W., Ballou DR., FitzGerald R., et al. Plasmonic enhancement in lateral flow sensors for improved sensing of E. coli O157:H7. Biosens Bioelectron. 2019; 126: 324–31. https://doi.org/10.1016/j.bios.2018.10.066.

32. Burel C., Teolis A., Alsayed A., et al. Plasmonic Elastic Capsules as Colorimetric Reversible pH-Microsensors. Small. 2020;16:1–9. https://doi.org/10.1002/smll.201903897.

33. Alaqad K., Saleh TA. Gold and Silver Nanoparticles: Synthesis Methods, Characterization Routes and Applications towards Drugs. J Environ Anal Toxicol. 2016; 6. https://doi.org/10.4172/2161-0525.1000384.

34. Ahmed S., Bui MPN., Abbas A. Paper-based chemical and biological sensors: Engineering aspects. Biosens Bioelectron. 2016; 77: 249–63. https://doi.org/10.1016/j.bios.2015.09.038.

35. Saudagar RB., Mandlik KT. A Review on Gold Nanoparticles. Asian Journal of Pharmaceutical Research. 2016; 6: 45–8. https://doi.org/10.5958/2231-5691.2016.00008.3.

36. Arora AK. Metal/ Mixed Metal Oxides and Their Applications as Sensors: A Review. Asian Journal of Research in Chemistry. 2018; 11: 497–504. https://doi.org/10.5958/0974-4150.2018.00089.5.

37. Chen X., Zhou G., Peng X., et al. Biosensors and chemosensors based on the optical responses of polydiacetylenes. Chem Soc Rev. 2012; 41:4610–30. https://doi.org/10.1039/c2cs35055f.

38. Chaiet L., Wolf FJ. The properties of streptavidin, a biotin-binding protein produced by Streptomycetes. Arch Biochem Biophys. 1964; 106: 1–5. https://doi.org/10.1016/0003-9861(64)90150-X.

Received on 09.12.2022 Modified on 17.02.2023

Research J. Pharm. and Tech 2023; 16(10):4663-4670.

DOI: 10.52711/0974-360X.2023.00758