Far From Any Lab, Paper Bits Find Illness
Todd Heisler/The New York Times
BIG DEAL A nonprofit company produces diagnostic tests the size of a stamp.
By Todd Heisler, Nancy Donaldson, Soo-Jeong Kang, Lisa Iaboni and Nick Harbaugh — Small Fixes: Paper Diagnostics: Donald G. McNeil Jr., a science reporter for The New York Times explains a liver damage test that fits on a postage stamp and could cost less than a penny.
The New York Times, by Donald G. McNeil Jr, September 27, 2011, BOSTON — While other scientists successfully shrank beakers, tubes and centrifuges into diagnostic laboratories that fit into aluminum boxes that cost $50,000, George Whitesides had smaller dreams.
Todd Heisler/The New York Times
The diagnostic tests designed in Dr. Whitesides’s Harvard University chemistry laboratory fit on a postage stamp and cost less than a penny.
His secret? Paper.
His colleagues miniaturized diagnostic tests so they could move into the field with tiny pumps and thread-thin tubes. Dr. Whitesides opted for a more novel approach, reasoning that a drop of blood or urine could wick its way through a square of filter paper without any help.
And if the paper could be etched with tiny channels so that the drop followed a path, and if that path were mined with dried proteins and chemically triggered dyes, the thumbnail-size square could be a mini-laboratory — one that could be run off by the thousands on a Xerox machine.
Diagnostics for All, the private company Dr. Whitesides founded four years ago here in Boston’s Brighton neighborhood to commercialize his inspirations, has already created such a test for liver damage.
It requires a single drop of blood, takes 15 minutes and can be read by an untrained eye: If a round spot the size of a sesame seed on the paper changes to pink from purple, the patient is probably in danger.
Using paper in diagnostic tests is not entirely new. It soaks up urine in home pregnancy kits and blood in home diabetes kits. But Dr. Whitesides has patented ways to control the flow through multiple layers for ever-more-complex diagnoses. His test has proved more than 90 percent accurate on blood samples previously screened by the laboratory of Beth Israel Deaconess Medical Center, a Harvard teaching hospital, said Una S. Ryan, chief executive of Diagnostics for All.
“They should be even more accurate on fresh blood,” added Dr. Ryan, a biologist. Field tests in India are set for later this year.
The initial target audience is AIDS patients with tuberculosis who must take powerful cocktails of seven or more drugs.
Some drugs damage the liver, and deaths from liver failure are 12 times as common among African AIDS patients as among American ones, Dr. Ryan said, because current liver tests are expensive and require tubes of blood.
The paper test was developed with a $10 million grant from the Bill and Melinda Gates Foundation.The foundation and the British government just donated $3 million toward creating three more paper tests to help small farmers. One is for aflatoxin, a poison produced by mold that grows on corn, peanuts and other crops. A large dose can lead to liver cancer, but even small amounts eaten regularly can leave children stunted. Farmers who can prove their crops are mold-free can protect their families and get higher prices. But current tests cost $6 each, far more than farmers can afford. A paper test that works on water washed over the grain could be made for as little as 50 cents, Dr. Ryan estimated. Volume production could drive the cost down to pennies.
The second test checks for milk spoilage caused by bacteria. Many small dairy farmers belong to cooperatives in which they pool their milk, and one sick cow can contaminate a whole batch.
The current test detects just the acidity caused by the bacteria, which is not very specific and can be defeated by adding a base like lime. A cheap enough test would help the cooperative find the offending farmer, and the farmer find the diseased cow.
The third proposed test detects hormones released into the urine when a cow is pregnant. Currently, farmers have to either watch their cows for behavior changes or perform physical exams that can be dangerous because they require reaching deep into the cow’s rectum to palpate the uterus.
“Raising cows is how farmers build wealth,” said Patrick Beattie, head of global health operations at Diagnostics for All. “They need better tests.”
The company’s office here is nothing fancy. The space is sublet from a nanotechnology company in an office park where pride of place belongs to an Acura dealership. Half the lab is piled with high-tech junk abandoned by a previous tenant.
And for all the elegance of the thinking that went into them, the tests themselves are produced in a remarkably low-tech, low-cost fashion. A sheet of filter paper, cut by hand, is fed into an $800 Xerox office printer that uses melted black wax instead of toner. Exactly 132 tests, resembling big shirt buttons, fit on an 8 ½-by-11-inch sheet.
The sheet is then placed for a few seconds into a heating box — one executive called it “our $5,000 Easy-Bake oven” — to melt the wax deeper into the paper, creating the channels.
(Originally, Dr. Whitesides used a plastic that hardened in ultraviolet light, but wax is cheaper and faster.)
Reagents are spotted on by hand with a pipette — a tedious job, but the $100,000 machine that can automate it is not in the budget, Dr. Ryan said. Then the paper “buttons” are cut out by a computer-driven scalpel.
Multiple layers are made this way, then glued into a sandwich and laminated.
Finally, each batch is sealed into a foil envelope to keep out moisture and sunlight.
In an interview in his office in Harvard’s main chemistry building, Dr. Whitesides described the origins of his idea.
Because cost was less of an issue for the military, expensive polymers could be used.
“But that was too expensive for the developing world,” he said, “so I was thinking, ‘What’s the minimum-cost way of making patterns, of putting things into test zones?’ And what came to mind was newspapers and comic books. And that led to these paper diagnostics.”
Dr. Whitesides sees many possible advances. The liver-function test uses chemistry. The next generation will use immunology — for example, one design has dried antibodies attached to bits of paint that drift over a surface to which other antibodies are fixed. The paint making it through gives the color reaction.
After that, he plans to build something like the battery-powered glucose meter used by diabetics, but on a disposable chip, employing flexible circuits printed with metal-infused ink and light-emitting diodes less than a millimeter across.
He also envisions a chip that will count how many cells in a drop of blood have malaria parasites inside.
Multiplying DNA, a key part of tests for viruses, is a bigger obstacle, since that usually requires repeated heating and cooling.
“I don’t see us doing sequencing,” he said. “That’s still going to be done in an aluminum box. But we’re still a long way from getting to the end of what’s inventable.”
For now, Dr. Whitesides is eager to see his inventions prove their usefulness in the real world.
“I’m going to breathe a sigh of relief when somebody says, ‘We’ve used up the first 10,000 in our clinic, and we think they’re absolutely terrific. Send us another 50,000.’ ”
Eventually, Dr. Ryan explained, the goal is for Diagnostics for All, which is nonprofit, to wean itself off grant money by licensing its chip technology to commercial companies.
For example, she said, marathon runners might be able to touch a chip to their sweaty foreheads to see if their electrolytes are still in balance before they drink more water. Or Americans with high cholesterol taking statins, which can also cause liver damage, might routinely monitor their liver enzymes with a finger prick.
Markets like those could give the company an income stream that would go a long way toward supporting its research in Africa, Dr. Ryan said.
“Although,” she added, “there will be huge pushback from the lab companies, because that’s their bread and butter.”
‘POSTAGE STAMP’ LIVER TEST
Dr. George Whitesides’s paper diagnostic test assesses the level of aspartate transaminase in the blood. The enzyme, better known as AST, is released when liver cells break down.
1. A drop of blood is touched to the back of the square of paper. It first seeps through a membrane with pores that block the large red and white blood cells, letting through only the clear plasma.
2. The next layer contains two dried chemicals, one of which is cysteine sulfinic acid, which is chemically similar to aspartate, the amino acid that AST normally binds to. (These chemicals are available from lab supply houses.)
3. If AST is present, it binds to the two chemicals, causing a reaction that ultimately releases sulfite ions, SO3.
4. The next layer contains a methyl dye that is normally blue but turns colorless when sulfites attach to it. It is printed over a pink background, so the spot looks purple. If the layer changes to light pink, the blood contains dangerous levels of AST.
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The Global Competitiveness Report 2011-2012
Switzerland tops the overall rankings in The Global Competitiveness Report 2011-2012. Singapore overtakes Sweden for second position. Northern and Western European countries dominate the top 10 with Sweden (3rd), Finland (4th), Germany (6th), the Netherlands (7th), Denmark (8th) and the United Kingdom (10th). Japan remains the second-ranked Asian economy at 9th place, despite falling three places since last year.
The United States continues its decline for the third year in a row, falling one more place to fifth position. In addition to the macroeconomic vulnerabilities that continue to build, some aspects of the United States’ institutional environment continue to raise concern among business leaders, particularly related to low public trust in politicians and concerns about government inefficiency. On a more positive note, banks and financial institutions are rebounding for the first time since the financial crisis and are assessed as somewhat sounder and more efficient.
Germany maintains a strong position within the Eurozone, although it goes down one position to sixth place, while the Netherlands (7th) improves by one position in the rankings, France drops three places to 18th, and Greece continues its downward trend to 90th. Competitiveness-enhancing reforms will play a key role in revitalizing growth in the region and tackling its key challenges, fiscal consolidation and persistent unemployment.
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The New Sustainability Champions
Meet the Technology Pioneers 2012: Innovating to Transform Society
- World Economic Forum selects 25 Technology Pioneers, visionary companies in the fields of information technology and new media, energy/environment and life sciences/health
- Technology Pioneers 2012 includes some of the world’s most innovative young companies whose cutting-edge technologies are transforming business and society
- Read their profiles or download the report at http://www.weforum.org/techpioneers
Geneva, Switzerland, 1 September 2011 – The World Economic Forum today announced its new class of Technology Pioneers, comprised of 25 of the most innovative technology start-ups from around the world. These companies represent the latest generation of innovation and are poised to have a critical impact on how business and society work.
The Technology Pioneers 2012 will be recognized for their work at the Annual Meeting of the New Champions in Dalian, People’s Republic of China, from 14 to 16 September 2011.
The Technology Pioneers 2012 are drawn from the fields of information technology and new media, energy and environment, and life sciences and health where they are active in a variety of areas, illustrating the broad range of impact they have on the world. Among their many diverse activities are drip irrigation on small farms to high-precision greenhouse-gas measurement; providing financial services to underserved, rural populations; and developing photosynthetic biofuels or molecular diagnostics.
“One particular aspect to highlight this year is the large number of companies that are focusing on having a social impact, such as providing health or financial services to underserved populations, while revolutionizing the business paradigms in their industries,” said Olivier Schwab, Director, Head of Technology Pioneers, World Economic Forum. “This year’s companies showcase the diversity in which innovative technology can be deployed to benefit business and society.”
The selected companies are (in alphabetical order): 1366 Technologies, Altobridge, Appirio, Attero Recycling, Biocartis, CloudFlare, Diagnostics For All, DoubleVerify, Driptech, Dropbox, EcoMotors International, Electro Power Systems, Financial Inclusion Network and Operations, First Energy, Joule Unlimited, Kickstarter, Lending Club, Living PlanIT, Mocana, Palantir Technologies, Picarro, Protean Electric, Solazyme, Tabula Digita and Tethys BioScience.
For further information on the Technology Pioneers 2012, please visit http://www.weforum.org/techpioneers.
The identification of the Technology Pioneer companies is the result of a rigorous selection process for which the Forum received hundreds of applications from around the world and that were evaluated by over 50 global technology experts. The selection committee includes leading academics, journalists, technologists and venture capitalists.
Since 2000, the World Economic Forum has recognized the work of young companies who hold the promise of significantly transforming the way business and society operate. More than 400 innovative companies from five continents have been selected as Technology Pioneers. Among them, approximately 60% are still independent and 20% have been acquired by industry leaders. Previous Technology Pioneers include Monitise (2006), Mozilla Corporation (2007), Nanosolar (2007), Gridpoint (2008), Mint.com (2009), BloomEnergy (2010), Takadu (2011) and NetQin (2011).
Technology Pioneers are selected on a yearly basis. Candidate companies are nominated by Members, constituents and collaborators of the World Economic Forum, as well as by the larger public. A selection committee, comprised of top technology and innovation experts from around the world, reviews all candidate companies and makes a recommendation to the World Economic Forum, which then takes the final decision.
Bloomberg TV, Innovators: Medicine. Diagnostics For All explains how we create our patterned-paper liver function tests and how they can be used to improve health in developing countries. Three companies are featured; DFA’s portion can be found here, or the entire episode can be watched here. (The segment on DFA begins at 0:07:08) Play »
March / April 2009
Technology Review, “TR10: Paper Diagnostics: George Whitesides explains how diagnostic paper chips could revolutionize health care in disparate places.” Play »
March / April 2009
Technology Review, “Making Paper Diagnostic Tests: The paper diagnostic chips are made in a few steps, shown here by graduate student Andres Martinez, a member of the Whitesides Research Group.” Play »
December 22, 2008
Charlie Rose, “An hour with Bill Gates” (roughly 26 minutes into the program) Play »
June 20, 2008
NYSE Euronext, “Diagnostics For All visits the NYSE to celebrate its unprecedented win of both the Harvard Business School and MIT Business Plan Competitions.” Play »
© 2011 Diagnostics For All