Technology

Paper Analytical Devices

Pad Comparison Maybe

 

Find fakes faster with PAD testing!

PADs are robust field screening tests that work for many different medications. The current card design is a complete lab on a piece of paper--the user does not need to add anything other than the medicine to be tested and water. The test card stores the reagents, mixes them in the correct order, and brings them to the drug sample. The user does not need any instruments or supplies, other than the test card itself.

 

Chemistry for detection of falsified drugs

The twelve lanes contain all the reagents needed to carry out tests for different chemicals and functional groups. For example, one lane contains copper(II) and a base; these materials give a characteristic forest-green color with any beta-lactam type antibiotic. That copper lane gives a different, and distinctive, color with metformin, which is a diabetes medication.  Another lane contains a series of reagents that generate a reactive species that can detect phenol groups, found in drugs like acetaminophen or amoxicillin. Other lanes specialize in detecting inert fillers like maize meal, or substitute drugs like acetaminophen that might be added to replace a more expensive medication.  We're always looking for more chemistry to expand the types of drugs we can detect.

The contents of a pharmaceutical generate a color bar code

The 12 lanes produce unique chemical fingerprints for many pharmaceuticals.  Some lanes can give more than one color, or can produce colors in different locations within the lane, depending on the ingredients present in the pill. The colors look a bit like a bar code.  Since computers are good at reading bar codes, we are developing computer software to read the test outputs automatically.

How well do the tests work?

To date, we have recorded unique color bar codes for more than 60 different pharmaceuticals with our current 12-lane PAD.  In some cases, the PAD can identify substandard pharmaceuticals based on differences in chemical composition. Shown below is an example of test outcomes for falsified (left) and authentic (right) Coartem. The fake contains an unexpected ingredient, which is not present in genuine Coartem. 

fake_and_real_coartem_on_pad

Fabrication of the test cards

The paper test cards contain a library of chemical color reactions, each isolated in its own reaction lane by hydrophobic barriers that are printed onto the paper using Whitesides-type wax printing. We start with Ahlstrom 319 chromatography paper, which is a heavy paper made of pure cellulose fibers. We use a color laser printer to print the QR code, color standards, and lane labels, then a Xerox ColorQube wax printer is used to print the lines that will separate the lanes. After a quick bake to make the wax soak into the paper, the test cards are stamped with the reagents and then cut out. We have made over 40,000 test cards.

Research bibliography  (email mlieberm@nd.edu to request a pdf of any publication behind a pay wall)

 

idPAD: Paper Analytical Device for Presumptive Identification of Illicit Drugs,, Lockwood, T.-L. E.; Leong, T. X.; Bliese, S. L.; Helmke, A.; Richard, A.; Merga, G.; Rorabeck, J.; Lieberman, M... Journal of Forensic Sciences. 2020, 65(4):1289-1297

Enzyme-based paper test for detection of lactose in illicit drugs.  Jessica Zinna*, Tracy-Lynn Lockwood*, Marya Lieberman.  Analytical Methods 2020, 12, 1077-1084, https://doi.org/10.1039/C9AY02459J

Paper Millifluidics Lab: Using a Library of Color Tests to Find Adulterated Antibiotics  Sarah L. Bliese*, Deanna O’Donnell, Abigail A. Weaver, Marya Lieberman.  J. Chem. Ed. 2020   http://dx.doi.org/10.1021/10.1021/acs.jchemed.9b00433

Substandard cisplatin found while screening the quality of anti-cancer drugs from Addis Ababa, Ethiopia.  Madeline D. Smith Eberle*,  Ayenew Ashenef,  Heran Gerba, Patrick Loehrer, and Marya Lieberman. Journal of Global Oncology, 2020, accepted manuscript.

Global access to quality-assured medical products: the Oxford Statement and call to action Newton, Paul N et al. The Lancet Global Health, 2019, 7(12), e1609 - e1611.  DOI:  https://doi.org/10.1016/S2214-109X(19)30426-7

Lab on Paper: Assay of Beta-Lactam Pharmaceuticals by Redox Titration.  N. M. Myers, M.W. Maina, P. M. Were, R. Karwa, S. D. Pastakia, J. C. Sharp, J. L. Luther, A. W. Cooper, S. L. Bliese, N. Oberhof, D. Aldulaimi and M. Lieberman, Anal. Methods, 2019, DOI: 10.1039/C9AY01547G.

Detection of Degraded, Adulterated, and Falsified Ceftriaxone Using Paper Analytical Devices, Sarah L. Bliese,  Mercy Wangechi Maina,  Phelix Makoto Were  and  Marya Lieberman, 2019, Analytical Methods, DOI: 10.1039/C9AY01489F

Paper Analytic Device to Detect the Presence of Four Chemotherapy Drugs, Madeline Smith, Ayenew Ashenef, and Marya Lieberman, 2018, Journal of Global Oncology, 4:1-10, DOI: https://doi.org/10.1200/JGO.18.00198, https://www.ncbi.nlm.nih.gov/pubmed/30589597

Identification of substandard and counterfeit antimalarial pharmaceuticals chloroquine, doxycycline, and primaquine using surface-enhanced Raman scattering.  Tackman EC, Trujillo MJ, Lockwood T-L E, Merga G., Lieberman M, and Camden JP. Anal. Methods, 2018,10, 4718-4722

Amoxicillin Quality and Selling Practices in Urban Pharmacies and Drug Stores of Blantyre, Malawi.  Chikowe, Ibrahim; Bliese,  Sarah L.*; Lucas, Samuel…; and Lieberman, Marya.  Am J Trop Med Hyg. 2018 99(1) 233-238. DOI: 10.4269/ajtmh.18-0003

Paper test card for detection of adulterated milk.  Luther, Jamie L. ], Henry deFreyhan, Valentine…, and Lieberman, Marya.  Analytical Methods, 2017, 9, 5674 - 5683.  DOI: 10.1039/c7ay01321c

Green design of a paper test card for urinary iodine analysis, Myers, Nicholas M. ]; Leung, Ivan C. …; McGee, Sean W. …; Eggleson, Kathleen; Lieberman, Marya. PLoS ONE  2017, 12(6) e0179716.  DOI: 10.1371/journal.pone.0179716.

A new analytical tool (saltPAD) for monitoring salt iodization in low resource settings, 2016, N. Myers, E. Strydom, J. Sweet, C. Sweet, M. A. Dhansay,  R. Spohrer, M. Lieberman, NanoBiomedicine  3:5 | doi: 10.5772/62919

Visual Recognition of Paper Analytical Device Images for Detection of Falsified Pharmaceuticals, S. Bannerjee, J. Sweet, M. Lieberman, P. Flynn, and C. Sweet, 2015, accepted for WACV 2016: IEEE Winter Conference on Applications of Computer Vision, March 7-9, Lake Placid NY. 

"Enabling the development and deployment of next generation  point-of-care diagnostics,"  Ratmir Derda, Jesse Gitaka, Catherine M. Klapperich, Charles R. Mace, Ashok A. Kumar, Marya Lieberman, Jacqueline C. Linnes, Joerg Jores, Johnson Nasimolo, Joseph Ndung’u, Evans Taracha, Abigail Weaver*, Douglas B. Weibel, Thomas M. Kariuki, and Paul Yager, 2015, PLOS Neg. Trop. Dis. Published: May 14, 2015 DOI: 10.1371/journal.pntd.0003676

"Part per million quantification of iodate in fortified salt using a paper device," N. M. Myers, Emalee Kernisan…, and M. Lieberman, Anal. Chem. 2015, 87, 3764-3770. DOI: 10.1021/ac504269q, pay wall

"Paper test cards for presumptive detection of very low quality anti-malarial medications," A. Weaver, M. Lieberman, Am J Trop Med Hyg Published online April 20, 2015; doi:10.4269/ajtmh.14-0384

"Incorporating yeast biosensors into paper-based analytical tools for pharmaceutical analysis," Weaver, A.;  Halweg, S. …;  Joyce, M.;  Lieberman, M.;  Goodson, H.,  Anal. Bioanal. Chem 2014, DOI 10.1007/s00216-014-8280-z

"Paper analytical devices for fast field screening of beta lactam antibiotics and anti-tuberculosis pharmaceuticals"  A. Weaver, H. Reiser…, T. Barstis, M. Benvenuti…, D. Ghosh, M. Hunkler…, B. Joy, L. Koenig…, K. Raddell…, M. Lieberman, Analytical Chemistry,  2013, 85 (13), 6453–6460 http://dx.doi.org/10.1021/ac400989p, pay wall

Other publications (conference)

  •  "Lab-on-paper developed to monitor iodized salt," N. Myers, M. Lieberman,  ICCIDD newsletter May 2014

  • "Paper analytical devices for detection of low-quality pharmaceuticals," A. Weaver* and M. Lieberman,  Proceedings of the SPIE - The International Society for Optical Engineering, 2014, Vol. 8976 89760H-1

  • "Catching the counterfeits," E. Bajema, T. Barstis, and M. Lieberman, Chemistry & Industry, 77: 28–30.  2013 doi: 10.1002/cind.7701_6.x

  • “Bounded Crowd Sourcing: A twist on open crowd sourcing offers promise for global health efforts,” M. Lieberman, E. Michael, and J. Bock, Monday Developments (a monthly magazine of in-depth news and commentary on global trends that affect relief, refugee, and development work as a service to U.S. humanitarian organizations), July 2011, 29(9), 27-28.

Video from Kenya's Daily Nation newspaper, Feb. 10, 2016