Table 4 New biomarker detection technologies.

From: The Assessment of the Readiness of Molecular Biomarker-Based Mobile Health Technologies for Healthcare Applications

Information about the Biomarker used for Testing the Detection Technology

Information about the Biomarker Detection Technology

Biomarker

Biomarker molecule type

Biomarker Source

Detected Disease Condition (Detection Type)

Biomarker Levels in Patients

Biomarker Levels in Normal Population

Biomarker Detection Technology

Product Cost

Lower Limit of Detection

Upper Limit of Quantification

Minimum Sample Volume

Detection Time

Technology Readiness for Detecting Biomarker in Non-invasive Source from Patients

Reference

Paper-based and mobile-phone enabled technologies

Human epididymis protein 4 (HE4)

Protein

Urine

Ovarian cancer (D)

364.5 ng/mL - 458.8 mg/mL

0.0574 ng/mL - 727.1 ug/mL

Paper-based ELISA + smartphone

N/A

19.5 ng/mL

1250 ng/mL

100 μL

5 h (may be cut to 15 min)

Within range

9

Mycobacterium tuberculosis nucleic acids

DNA

N/A

Tuberculosis (D)

N/A

N/A

Paper-based Au-nanoprobes + smartphone

N/A

10 μg/mL

N/A

5 μL

65 min (2h30min including PCR amplification)

N/A

12

MMP9

Protein

Urine

Colorectal cancer (D)

N/A

N/A

Paper lateral flow assay + smartphone/scanner

$2.60 + cost of cellphone

92 ng/mL

644 ng/mL

5 μL

N/A

N/A

15

Thrombin

Protein

Urine

Thrombosis (D)

N/A

N/A

Paper lateral flow assay + smartphone/scanner

$2.60 + cost of cellphone

72 ng/mL

504 ng/mL

5 μL

N/A

N/A

15

Neuropeptide Y

Peptide

Saliva

Post-traumatic stress disorder (P, T)

∼1.7–5.95 pg/mL(plasma)

0.014–0.065 pg/mL (saliva), ∼0.21–2.42 pg/mL (plasma)

Paper-Based ELISA + camera/smartphone/scanner/printer

Low cost

127.59 ng/mL

21.265 μg/mL

3 μL

<60 min

Out of range

22

Hepatitis B virus plasmid DNA

DNA

N/A

Hepatitis B (D)

N/A

N/A

Convective polymerase chain reaction + smartphone

N/A

30 copies per reaction

N/A

3 μL

20 min

N/A

48

VEGF

Protein

Inner eye aqueous humor

Proliferative diabetic retinopathy, age-related macular degeneration, retinal vein occlusion (D)

740.1 ± 267.7 pg/mL, 383 ± 155.5 pg/mL, 219.4 ± 92.1 pg/mL

14.4 ± 8.5 pg/mL

Paper-based ELISA + Smartphone

Cost of paper-ELISA + cost of cellphone

33.7 fg/mL

10 μg/mL

2 μL

44 min

Within range

24

Paper-based technologies

Chorionic gonadotropin

Protein

Urine

Pregnancy (D)

>2.5 ng/mL

<0.5 ng/mL

Automated paper-based sequential multistep ELISA. + inkjet printing

Low cost

0.81 ng/mL

500 ng/mL

50 μL

15–25 min

Within range

49

HIV-1 envelope antigen gp41

Protein

Serum

HIV infection (P)

N/A

N/A

Paper-based ELISA + scanner

Cost of paper-ELISA + $100 for scanner

N/A

N/A

<20 μL

<60 min

N/A

25

Anti-Leishmania antibodies

Protein

Canine blood

Leishmaniasis (D)

N/A

N/A

Paper-based ELISA + scanner

Cost of paper-ELISA + $100 for scanner

1 mg/mL

N/A

μL range

60 min

N/A

12

Anti-NC16A autoimmune antibodies

Protein

Blister fluid

Bullous pemphigoid (D)

N/A

N/A

Paper-Based ELISA + desktop scanner

Cost of paper-ELISA + $100 for scanner

3 ug/mL

50 μg/mL

2 μL

70 min

N/A

50

Lactoferrin

Protein

Tear

Dry eye syndrome (D)

0.13 ± 0.22 mg/mL

2.05 ± 1.12 mg/mL

An inkjet-printed microfuidic paper-based analytical device + digital camera

$0.0131 per testing sheet + cost of digital camera

5 ng/mL

50 ng/mL

2.5 μL

15 min

Within range after dilution

13, 51

Mobile-phone enabled technologies

Plasmodium falciparum histidine-rich protein 2 (PfHRP2)

Protein

Serum, Saliva

Malaria (D)

17–1167 pg/mL (saliva)

0

A disposable microfluidic chip + smartphone with embedded circuit

N/A

16 ng/mL

1024 ng/mL

0.5 μL

15 min

Out of range

26, 52

Bacterial DNA

DNA

N/A

Bacterial infection (D)

N/A

N/A

A disposable micro?uidic chip with primers + a fluorescence detector + smartphone

$350-$600

760 DNA copies per μL

N/A

30 μL

30 min

N/A

33

Interferon-gamma

Protein

N/A

Latent tuberculosis (D)

48.69 ± 28.78 pg/ml (blood)

12.99 ± 5.70 pg/ml (blood)

An opto-acoustic immunoassay + mobile phone technologies ( surface acoustic wave transducer, CMOS camera, LED)

low cost

17.15 pg/mL

17.15 ng/mL

N/A

10 min

Within range

27, 53

Adenovirus DNA

DNA

N/A

Viral infection

N/A

N/A

A microfluidic capillary array + an optical signal amplifier (multi-wavelength LEDs) + smartphone

$180 for capillary array + cost of LED and smartphone

0.4 ug/mL

5 μg/mL

10 μL

N/A

N/A

28

Cortisol

Small molecule

Saliva

Stress, anxiety, depression (D)

20.7–37.3 ng/mL

0.4–14.1 ng/mL

Chemiluminescent lateral flow Immunoassay + smartphone with custom-designed 3D printer

Low cost

0.3 ng/mL

60 ng/mL

25 μL

30 min

Within range

54, 55

N-terminal proBNP molecule

Peptide

Blood

Heart failure (D,P)

1076 ± 138 pg/mL

38 ± 4 pg/mL

A disposable biomarker sensing element + HDR image acquisition technique + computer screen photo-assisted technique + smartphone

N/A

60 pg/mL

3000 pg/mL

150 μL

12 min

Within range

30, 56

IL-6

Protein

Serum

Cancer (P)

300- 3500 pg/mL

<300 pg/mL

ELISA + smartphone

N/A

2 pg/mL

N/A

N/A

2 hour 40 min

Within range

57

Albumin

Protein

Urine

Kidney disease (D)

>30–300 ug/mL

<30 ug/mL

Fluorescent assay in disposable test tubes + smartphone

$190 + cost of phone

5–10 μg/mL

200 μg/mL

25 μL

5 min

Within range

26

Other lab-on-a-chip platform technologies

Apolipoprotein A1

Protein

Urine

Bladder cancer (D)

207.3 -3754.7 ng/mL

~ 10 ± 8 ng/mL

A negative-pressure-driven microfluidic chip magnetic bead based ELISA + optical measurment device

lower costs than conventional ELISA

10 ng/mL

2000 ng/ml

14.5 μL

40 min

Within range

31, 32

Minimally invasive finger-prick biomarker technologies

C-reactive protein

Protein

Blood

Prostate cancer, colorectal cancer (P),

>3 ug/mL (blood)

<1 ug/mL (blood)

A microtiterplate based ELISA + smartphone

<$660

0.3 ng/mL

81 ng/mL

N/A

<30 min

Within range after dilution

29, 58

HIV-1 gp41 and HIV-2 gp36

Protein

Blood

HIV infection (P)

N/A

N/A

A low-power, low-cost and compact smartphone dongle of microfluidic ELISA

$34 + + cost of cellphone

10 μg/mL

N/A

2 μL

15 min

N/A

59, 60

N-terminal proBNP molecule

Peptide

Blood

heart failure (D,P)

1076 +_ 138 pg/mL

38 +_ 4 pg/mL

A disposable biomarker sensing element + HDR image acquisition technique + computer screen photo-assisted technique + smartphone

N/A

60 pg/mL

3000 pg/mL

150 uL

12 min

Within range

30, 56

Antibodies against HIV

Protein

Blood

HIV (D)

>0

0

A mobile microfluidic chip for immunoassay

$0.1 per cassette + $0.5 light-emitting diodes+ $6 photodetector + cell phone

N/A

N/A

1 uL

20 min

Within range

39

Antibodies against Treponema pallidum

Protein

Blood

syphilis (D)

>0

0

A mobile microfluidic chip for immunoassay

$0.1 per cassette + $0.5 light-emitting diodes+ $6 photodetector + cell phone

N/A

N/A

1 uL

20 min

Within range

39

Prostate-specific antigen (PSA)

Protein

Blood

Prostate cancer (D)

>4 ng/mL

<4 ng/mL

A microfluidic purification step + label-free nanosensor detection

low cost

1.5 ng/mL

N/A

10 uL

20min

Within range

40

Carbohydrate antigen 15.3 (CA15.3)

Protein

Blood

Breast cancer (D)

>30 U/ml

<30 U/ml

A microfluidic purification step + label-free nanosensor detection

low cost

15 U/mL

N/A

10 uL

20min

Within range

40

Haemoglobin

Protein

Blood

Anaemia (D)

N/A

N/A

       

38

Aspartate aminotransferase (AST)

Protein

Blood

Tuberculosis/HIV (T)

N/A

5−40 U/L

A paper-based, multiplexed microfluidic assay

<$0.10 per test

84 U/L

N/A

15 uL

15 min

Within range

42

Alkaline phosphatase (ALP)

Protein

Blood

Tuberculosis/HIV (T)

N/A

30−120 U/L

A paper-based, multiplexed microfluidic assay

<$0.10 per test

53 U/L

N/A

15 uL

15 min

Within range

42

Aspartate aminotransferase (AST)

Protein

Blood

Hepatitis (D)

Acute : ~400 U/L, Chronic: ~ 160 U/L

5−40 U/L

A micropatterned paper-based microfluidic device + cellphone

low cost

44 U/L

400 U/L

15 uL

15 min

Within range

35

Alkaline phosphatase (ALP)

Protein

Blood

Liver conditions (D)

N/A

30−120 U/L

A micropatterned paper-based microfluidic device + cellphone

low cost

15 U/L

400 U/L

15 uL

15 min

Within range

35