Biosensors in Health Care: The Milestones Achieved in Their Development towards Lab-on-Chip-Analysis

Table 1

Recently developed biosensors along with their principles of working and applications.

Sl. number	Analyte	Biorecognition element	Sample	Technology	Advantages	References
1	Ebola, dengue, and yellow fever virus	Antibody tagged multicolored silver nanoparticles onto small strip of paper	Blood	Paper strip based multiplex disease diagnostics	Detecting down to tens of ng/mL	[43]
2	Ebola virus glycoprotein	Fe3O4 magnetic nanoparticle (nanozyme)	Blood	Nanozyme strip	Lower detection limit: 1 ng/mL	[44]
3	Urinary pathogens like E. coli and Enterococcus faecalis	Glass-polymer hybrid chip forms a centrifugal microfluidic platform that captures bacteria directly	Urine sample	Microfluidics and Raman microscopy	Detection within 70 minutes	[45]
4	Candida infection	Nanoparticles with supermagnetic properties coated with target-specific binding agents	Blood	Miniaturized magnetic resonance that measures water molecules reaction in the presence of magnetic fields	91.1% sensitivity, 99.4% specificity, and 1 CFU/mL (colony forming unit per milliliter)	[46]
5	Circulating tumor cells (CTC): metastatic breast, prostate, and melanoma cancers	The microchip allows microfluidic path in many rows through which the blood is pushed through	Blood	Microfluidic chip called cluster chip. CTC clusters are isolated through specialized bifurcating rows under low pulling forces preserving their integrity	At blood flow rate of 2.5 mL/hr, chip captured 99% of four- or more cell clusters, 70% of three-cell clusters, and 41% of two-cell clusters	[47]
6	Antibiotic sensitivity of bacteria	Series of minute flow-through wells patterned onto a glass chip. Each microwell coated with microbeads to trap the bacteria with the antibiotic and the signal molecule resazurin	Bacterial culture	Electrochemical reduction signal brought by the metabolism of resazurin in resistant bacteria, detected by the electrodes built on the chip	Bacterial resistance profile available within an hour of incubation	[48]
7	Ebola virus: glycoprotein (GP), nucleoprotein (NP), and viral matrix protein (VP40)	3 mouse monoclonal antibodies against each of the proteins	Blood	Chromatographic/lateral flow immunoassay; SD biosensor product used for WHO EUAL Program (Emergency Use Assessment and Listing)	Sensitivity, 84.9% (95% CI ) (78.6–91.2); specificity, 99.7% (95% CI) (99.1–100.0)	[49]
8	Blood glucose (noninvasive)	Nanoengineered silica glass with ions that fluoresce in infrared light when a low power laser light hits them	Skin touch to the glass (no finger prick required)	Low-powered lasers penetrate the skin and measure the length of time the fluorescence remains and calculate the blood glucose	Wearable, noninvasive device	[50]
9	Mycobacterium tuberculosis	Surface modified cadmium-telluride quantum dots, gold nanoparticles, and two specific oligonucleotides against early secretory antigenic target 6	Sputum	Sandwich form FRET based biosensor to detect M. tuberculosis complex and differentiate it from M. bovis bacillus Calmette-Guerin (present in vaccinated individuals)	94.2% sensitivity and 86.6% specificity, 10-fold lower detection limit	[51]
10	Microcystis spp. (MYC)	Sequence-selective DNA probe to MYC and redox surface modified with ionic liquid and pencil graphite electrode	Biological sample	Electrochemical DNA biosensor using differential pulse voltammetry (DPV)	Lower detection limit: 3.72 µg/mL	[52]
11	Human epidermal growth factor receptor 2 (HER2) protein in breast cancer cells	Anti-HER2 immobilized to nanoconducting film tagged to a biconjugate of hydrazine-gold nanoparticle aptamer	Blood and other body fluids	Electrochemical nanobiosensor where hydrazine acts as electrocatalyst and aptamer as reporter molecule	Ultrasensitive detection limit up to 26 cells/mL of human serum sample	[53]
12	Acoustofluidic sputum liquefier	Micromixer using oscillating sharp edges	Sputum	Microfluidic-based on-chip liquefaction device	Liquefying sputum samples at a throughput of 30 µL/min	[54]
13	Pathological biomarkers	The bacterial cell acts as a diagnostic agent by inserting a “transcriptor,” equivalent of a computer program into its DNA. The bacteria act as sensor modules to detect disease signals (molecular signals that control gene expression) in clinical samples	Blood and urine	Whole cell biosensors called “bactosensors.” They are genetically encoded digital amplifying genetic switches that perform signal digitization and amplification, multiplexed signal processing with the use of Boolean logic gates, and data storage	Transcriptor amplification ability could be used to detect very small amount of biomolecules in biological samples; for example, the transcriptor connected to bacterial system that responds to glucose could detect pathological glycosuria in diabetic patients	[55]
14	Urogenital schistosomiasis	Sensor surface modifies with oligonucleotide probes targeting the 16S rRNA of uropathogen. Cells in samples are lysed, tagged with detector probe and layered sensor surface	Urine	Electrochemical biosensor composed of three gold electrodes suitably modified with capture probes. Enzyme tag mediates an amperometric signal output proportional to the quantity of the target	Can detect the presence of pathogen in an hour	[56]
15	Cervical cancer	Microbeads coated with anti-EpCAM (epithelial cell adhesion molecule), anti-CD44, and anti-TACD@/Trop2 (tumor associated calcium signal transducer 2)	Abnormal PAP smear	Smartphone imaging system called D3 (digital diffraction diagnosis). It consists of battery-powered LED light with high resolution imaging data with camera	Capable of imaging 10 megabytes of data in 0.09 secs The D3 system can categorize the biopsy samples as high risk, low risk, or benign comparable to that of conventional histology	[57]
16	Human IgG in early prostate cancer	Citrate ligands-capped gold nanoparticles are mixed with blood sera forming a protein corona around the nanoparticle surface	Blood	Gold nanoparticle enabled dynamic light scattering assay (NanoDLSay)	It shows 90–95% specificity and 50% sensitivity	[58]
17	Molecular markers	Antibody against the specific biomarker	Biological samples	Optical fluorescence spectroscopy (OFS). It consists of microfluidic channel embedded with interdigitated microelectrodes array, analyte manipulation system, and novel amplification strategy for the binding signal and highly sensitive CMOS phototransistor (complementary metal oxide semiconductor)	It is a “multi-labs-on-chip” that shows sensitivity for ultra-low level in attomolar (10–18 M) concentration of biomarkers	[59]