Emerging technologies for next-generation point-of-care testing

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Emerging technologies for next-generation point-of-care testing

Sandeep Kumar Vashist ^a*, Peter B. Luppa ^a, Leslie Y. Yeo ^b, Aydogan Ozcan ^c,d,e and John H.T. Luong ^f*

^a Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, D-81675 Munich, Germany.

^bMicro/Nanophysics Research Laboratory, RMIT University, Melbourne, VIC 3001, Australia.

^cElectrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

^dBioengineering Department, University of California, Los Angeles, CA 90095, USA.

^eCalifornia NanoSystems Institute (CNSI), University of California, Los Angeles, CA 90095, USA.

^fInnovative Chromatography Group, Irish Separation Science Cluster (ISSC), Department of Chemistry and Analytical, Biological Chemistry Research Facility (ABCRF), University College Cork, Cork, Ireland.
*Corresponding authors. (SKV) E-mail: sandeep.vashist@tum.de; Tel.: +49 89 41404071; Fax: +49 89 41404875. (JHTL) E-mail: j.luong@ucc.ie

Supplementary Table S1. Cell phone-based point-of-care testing (CP-POCT).

Types	Analyte(s) detected	Characteristics	Ref.
Colorimetric detection	Peanut	Detects 1-25 ppm of peanut within 20 min	[1]
	25-hydroxyvitamin D	AuNP-based immunoassay (IA), linear detection range (LDR): 15-110 nM	[2]
	Herpesvirus nucleic acid	DNA sequences [1 mM] from Kaposi’s sarcoma associated herpes virus (KSHV) using a nanoparticle (NP) assay in microfluidic chips	[3]
	CRP	CRP [0.035-0.182 µg mL^-1] with limit of detection (LOD) of 0.026 µg mL^-1	[4]
	CRP	Rapid sandwich IA for CRP [0.3-81 ng mL^-1] with LOD of 0.4 ng mL^-1 using a smartphone-based colorimetric reader	[5]
	Cortisol	Detects cortisol in 10 min with LDR of 0.01-10 ng mL^-1 and LOD of 0.01 ng mL^-1	[6]
	Cholesterol	Detects the total cholesterol level in blood [140-400 mg dL^-1] within 1 min	[7]
	Proteases	A quantum dot (QD) based multiplex assay for the activity of trypsin, chymotrypsin and enterokinase [pM-nM]	[8]
	Cocaine	AuNP and aptamer-based assay for cocaine with LDR of 0.2-0.8 mg mL^-1	[9]
	HE4	Microchip ELISA for HE4 in urine with LDR of 19.5-1250 ng mL^-1 and LOD of 19.5 ng mL^-1	[10]
	Hg²⁺	Plasmonic AuNP and aptamer-based assay for Hg²⁺ with LOD of ~3.5 ppb	[11]
	Albumin	Detects albumin in the LDR of 0-100 mg dL^-1 with LOD of 6 mg dL^-1	[12]
	Glucose	Detects glucose in the LDR of 0-300 mg dL^-1 with LOD of 40 mg dL^-1	[12]
	Triplex detection of infectious diseases	Detects HIV antibody, treponemal specific antibody for syphilis, and non-treponemal antibody for active syphilis infection in 15 min	[13]
	Mumps, measles and herpes simplex virus IgGs	CP-based hand-held micro-plate reader based ELISAs for mumps, measles and herpes simplex virus IgGs	[14]
	Multi-analyte sensing arrays	An image processing algorithm for ascorbic acid, glucose, protein, ketones, urobilinogen, bilirubin and RBC using paper-based urine strips	[15]
	Heavy metals (Cu²⁺, Ni²⁺, Cd²⁺ and Cr⁶⁺)	Detects Cu²⁺, Ni²⁺, Cd²⁺ and Cr⁶⁺ with LODs of 0.29, 0.33, 0.19 and 0.35 ppm, respectively	[16]
	2,2ʹ,4,4ʹ-tetrabromodiphenyl ether (BDE-47)	Detects BDE-47 in the LDR of 10^-3-10⁴ ng mL^-1 using CP-interfaced lab-on-a-chip device based ELISA	[17]
Fluorescent detection	M. tuberculosis	M. tuberculosis bacilli in Auramine O-stained sputum smears.	[18]
	Salmonella typhimurium DNA	A fluorescent microscope and paper microfluidics-based assay for detecting S. typhimurium down to 10⁴ CFU mL^-1	[19]
	DNA amplification	Detects the DNA fragment of the Hepatitis B virus plasmid by convective polymerase chain reaction (cPCR)	[20]
	Recombinant bovine somatotropin (rbST) Abs	Detects rbST Abs in milk extracts by an IA using magnetic polystyrene microspheres and QD-labelled detection Ab	[21]
	Salmonella and E.coli O157	Lateral flow IA (LFIA) strips for Salmonella and E. coli O157 with LOD of 10⁵ CFU mL^-1	[22]
	β-D-galactosidase	A paper microfluidics-based IA for β-D-galactosidase, with LDR of 0.7-12 nM and LOD of 0.7 nM	[23]
	Single NPs & viruses	Fluorescent imaging of isolated 100 nM fluorescent NPs and human cytomegaloviruses	[24]
	microRNA	Fluorescent molecular beacon assay to detect microRNA with LOD of 10 pM.	[25]
	Red blood cells (RBCs) White blood cells (WBCs) Haemoglobin (Hb)	Imaging cytometry platform for Hb concentration and the density of RBCs and WBCs	[26]
	E. coli	Detects E.coli O157 by QD-based sandwich IA in glass capillaries with LOD of ~5-10 CFU mL^-1	[27]
	WBCs Giardia lamblia cysts	Imaging labelled WBCs in whole blood and water-borne pathogenic Giardia lamblia cysts [resolution of 10 µm and FOV of 81 mm²]	[28]
	Trypanosoma cruzi	T. cruzi genomic DNA [0.1 to100 fg µL^-1] with LOD of 9.6 ag	[29]
	Collagenase and Trypsin	Detects collagenase and trypsin with LODs of 3.75 µg mL^-1 and 930 pg, respectively, using a simple CP and tablet-based fluorescence detection system	[30]
Luminescent detection	Bile acid	An lateral flow assay (LFA) minicartridge format for total bile acid in serum and oral fluid with LDR and LOD of 0.5-100 µM and 0.5 µM	[31]
	Cholesterol	LFA minicartridge format for total cholesterol in serum with LDR and LOD of 20-386 mg dL^-1 and 20 mg dL^-1	[31]
	Salivary cortisol	LFIA for salivary cortisol [0.3-60 ng mL^-1] with LOD of 0.3 ng mL^-1	[32]
Spectrophotometric detection	microRNA	CP fluorimeter system to detect specific microRNA sequence with LOD of 10 pM using molecular beacon FRET assay	[33]
	Additives in beverages and food	CP-based spectroscopic analysis using CP’s screen for illumination and front camera for imaging.	[34]
SPR detection	β2 microglobulin (β2M)	Angle-resolved SPR detection system for β2M with LOD of 0.1 µg mL^-1	[35]
	Glycerol	Fiber optic SPR sensor to detect glycerol concentrations of 0-20%	[36]
	IgG	Fiber optic SPR sensor to detect various concentrations of IgG binding to protein A-bound sensing element	[37]
Electrochemical detection	Plasmodium falciparum histidine-rich protein 2 (PfHRP2) biomarker for malaria,	Detects PfHRP2 in 15 min with LOD of 16 ng mL^-1 using a compact embedded circuit, disposable microfluidic chip and capillary flow	[38]
	blood glucose and trace heavy metals (Pb²⁺, Cd²⁺, Zn²⁺) in water, Na⁺ in urine, and PfHRP2	Universal low-cost CP-based electrochemical detector for the detection of blood glucose and heavy metals in water, Na⁺ in urine, and PfHRP2 biomarker	[39]
	2,4,6-trinitrotoluene (TNT)	A CP-based electrochemical biosensor, using screen-printed electrodes modified with TNT-specific peptides, to detect TNT with LOD of 1 µM	[40]
	iHealth Wireless Smart Gluco-Monitoring System	Detects pathophysiological blood glucose concentrations using a miniaturized glucometer interfaced with SP via a smart application	[41]
	iHealth Align	Detects pathophysiological blood glucose concentrations using the smallest Food and Drug Administration (FDA) approved blood glucose meter	[42]
	Escherichia coli	CP-based electrochemical biosensor pre-concentrates E.coli and detects it with a LDR and LOD of 10-100 cells mL^-1 and 10 cells mL^-1, respectively	[43]
	Nitrate	Audio jack-based electrochemical sensor that detects nitrate concentration in water with LOD of 0.2 ppm and LDR of 1.4-70 ppm within 1 min	[44]
Cytometry	Optofluidic fluorescent imaging-based flow cytometer	Compact, light-weight and cost-effective CP-based flow cytometer with fluorescent resolution of ~2 µm and capability to analyze samples >0.1 mL	[45]
	RBCs, WBCs and Hb	Determines the density of RBCs, WBCs and Hb in blood from a 10 µL sample	[26]
Other detection techniques	Microscopy and spectroscopy	Stained and unstained blood smears, and transmission and fluorescence spectroscopy of diffuse tissue	[46]
	Unlabelled DNA	Monitoring the electrochemical dissolution of chromium electrode array in a microfluidic system	[47]
	Malaria, TB, HIV	CP-based integrated reader for malaria, TB and HIV	[48]
	RBCs & WBCs	A glass-based tapered fiber-optic array and multi-frame imaging for RBCs and WBCs in transmission mode	[49]
	Salmonella and E.coli	A paper microfluidic device and a Mie scattering-based IA for Salmonella and E. coli (10²-10⁵ CFU mL^-1)	[50]
	P. falciparum-infected and sickle RBCs	CP-based microscope for the bright field imaging of P. falciparum-infected and sickle RBCs in blood smears	[18]
	Thyroid stimulating hormone (TSH)	CP-based Mie scatter optimized LFA for TSH with LOD of 0.4 mIU L^-1	[51]
	Aflatoxin B1 (AFB1)	Reader and LFIA using a competitive binding format for AFB1 with linearity of 5-1000 µg kg^-1 and LOD of 5 µg kg^-1	[52]
	Single molecules	CP-based system using plasmonic substrates to detect surface enhanced Raman signals from solids and liquids	[53]
	Hepatitis B and Human Immunodeficiency Virus (HIV)	Detection of biomarkers for Hepatitis B and HIV in nM range using a CP camera and an optomechanical cradle that monitors the intensity of light reflected by the surface using the CP’s LED for illumination	[54]

Supplementary Figure S1. (A) Schematic of a CP-based device for the colorimetric detection of Hg²⁺ [11]. Reprinted with permission from the American Chemical Society. (B) vitaAID accessory on an iPhone for the colorimetric detection of vitamin D [2]. Reprinted with permission from the Royal Society of Chemistry. (C) CP attachment and minicartridge for biochemiluminescent detection of cholesterol [31]. Reprinted with permission from the American Chemical Society. (D) A CP-based colorimetric reader using screen-based bottom illumination provided by gadgets [5]. Reprinted with permission from the Elsevier B.V. (E) CP attachment for wide-field fluorescent and dark field imaging along with its schematic [28]. Reprinted with permission from the Royal Society of Chemistry. (F) Schematic of a CP-based fluorescence microscope and its ray-tracing diagram [24]. Reprinted with permission from the American Chemical Society (G) A CP-based contact microscopy platform and a schematic of the CP attachment [49]. Reprinted with permission from the Royal Society of Chemistry.

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