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Biotechnology for Global Health: Solutions for the Developing World

Consilience: The Journal of Sustainable Development

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Title Biotechnology for Global Health: Solutions for the Developing World
 
Creator Chin, Curtis; Columbia University
 
Description Identifying and developing emerging biotechnologies is important in improving health in the poorest nations because current health products and practices are not suited for their underdeveloped economies, their inadequate transport and power infrastructures, their largely rural populace, and their rugged, often tropical environments. Advances in biotechnology will more likely be valued and adopted as innovations in developing countries if they meet these challenging criteria. These innovations in health will favor a shift away from a centralized, curative-based framework towards a decentralized, prevention-based paradigm. In this article, advances in microfluidics and in vaccine delivery and storage are highlighted in the context of disease diagnosis and prevention in the developing world. What is the link between scientific discovery, biotechnology, and innovation, and why is biotechnology particularly important for improving health in the world’s poorest nations? One can think of scientific discovery and innovation as being on two opposite sides of a continuum. Scientific discovery deals with acquiring new knowledge and correcting and integrating previous knowledge by formulating testable hypotheses, conducting experiments, collecting data, and interpreting results to form conclusions. Scientific discovery is largely carried out in universities and is often characterized by academic freedom and intellectualism. On the other end of that continuum lies innovation, which introduces a new product or process that is both valuable to adopters and disruptive to the status quo. Unlike scientific discovery, innovation is driven by economic and social pressures, and creates wealth or social welfare to a group of people, an organization, or a society, by improving quality, efficiency, and productivity. In the middle of the continuum lies translational research, where discoveries with the potential of creating value are identified and pursued, and is conducted largely by the private sector. In the context of health products and practices, this middle ground is the domain of biotechnology. Innovations in products (such as drugs, vaccines, medical devices and equipment) start from scientific discoveries in genomics-related sciences (such as molecular biology, cell biology, immunology, genetics, biochemistry, and microbiology) and in applied sciences or engineering (such as bioengineering and biomedical engineering). Advances in biotechnology become innovations if they are considered valuable (in demonstrating clinical efficacy, ease of administration/use, reducing costs, etc.) and are adopted by health workers, health ministries, companies and organizations. Unlike scientific discovery, which is a long-term investment associated with high-risks, advances in biotechnology may directly lead to innovation and therefore contribute value to health sooner rather than later. But more importantly, underdeveloped countries cannot sustain the adoption of conventional medical products (in developed countries). Most conventional products and practices are incompatible with their weak economies, with their underdeveloped transport and power infrastructures, with their largely poor and rural populations, and with their rugged and often tropical environments. Despite these challenges, developing countries are perhaps best positioned to adopt innovations due to developments in biotechnology. Not only do their circumstances pose significant challenges that demand creative and valuable solutions, but also the significant gains over current health products and practices in underdeveloped countries (which may be inadequate or nonexistent) may accentuate an innovation’s value from an advancement in biotechnology. Specifically, this value can range from reducing early mortality and burden of disease (with more effective recombinant vaccines), and to preventing degradation of vaccines (by creating/optimizing techniques for stable formulations that withstand large fluctuations in heat and humidity), to increasing portability and capability of diagnostic devices (with miniaturized lab-on-a-chip technology). In short, the impetus for innovation in health is huge. Already there have been instances of widespread adoption of relevant (non-health) innovations. For example, the adoption of cell phones and wireless internet in sub-Saharan Africa bypassed the historical precedent of developing landlines, thereby allowing quick communication to rugged and remote places without developing significant infrastructure,But mere adoption of technology may not be enough in developing appropriate health products; tuning promising biotechnologies and even developing new ones may be needed. By doing so, developing countries may be able to “leapfrog” over conventional medical technologies which exist in centralized health systems (such as hospitals for healthcare and labs for diagnostic results), to innovations in health which are suited for decentralized health networks (such as point-of-care diagnosis and at-village/home healthcare) and that emphasize cost-effective public health strategies (such as disease prevention and epidemiological surveillance) In identifying and developing promising biotechnologies, it is important to first understand the limitations of conventional health products in meeting the unique challenges in underdeveloped settings. These limitations can be divided into several major categories: (1) power (e.g. lack of ground electricity, lack of refrigeration), (2) ease of use/administration (e.g. lack of skilled workers), (3) efficacy (e.g. sensitivity and specificity for diagnostics, development of immunity for vaccines), (4) portability (e.g. potential for use at rural villages or at point-of-care), (5) cost (e.g. costs associated with the product itself versus those for peripherals), and (6) safety. This article focuses on identifying two active areas of biotechnology research relevant to health in developing countries: vaccines (for building immunity against infectious diseases) and microfluidics (for point-of-care diagnostics). Each section highlights the limitations of current products in the settings of developing countries, and discusses what advantages (and possible disadvantages) emerging biotechnologies have in these areas. Vaccines – Novel storage and delivery strategies Vaccines for childhood illnesses - widely considered as essential in any strategy for disease prevention in developing and developed countries alike - have benefited greatly from recombinant DNA technologies. Not only are recombinant vaccinesalready proving to be cheaper (in testing and scale-up of production) and safer (particularly in immunocompromised individuals) than inactivated or attenuated vaccines, they also may address problems with vaccine storage and delivery. Normally, vaccines require refrigeration, needles, and multiple administrations to fortify or refresh immunity. But in much of the developing world, refrigeration is unavailable - and when available, refrigeration can constitute up to 80% of the total cost of vaccine delivery. Additionally, needles are often misused by inexperienced personnel in unsanitary conditions, leading to transmission of bloodborne pathogens such as HIV, HBV, and HCV. Patient noncompliance is commonplace as well with poor rates of return visits, thereby making multiple vaccine administrations difficult. These issues can be addressed partially by developing novel storage techniques (often by using/optimizing established processes with new formulations) in order to increase vaccine viability, and by researching different ways of administering vaccines (to reduce the need for intravenous immunizations). For example, the Bacillus Calmette-Guérin vaccine (BCG) currently is prepared commercially by freeze-drying, which is known to significantly reduce BCG viability after freezing. Researchers at Harvard University hypothesized that the presence of nonvolatile salts and cryoprotectants during normal droplet drying raised osmotic pressures high enough to damage bacterial membranes which yielded low vaccine viability and stability at room temperature. They discovered that spray drying (another dehydration method) with a special protein matrix without salts and cryprotectants yielded improved viability and stability. This is promising given the potential of spray dried vaccines to be inhaled (instead of delivered intravenously which is invasive) and scaled-up in sterile conditions with lower operating costs as compared to freeze-drying methods,. Already, Medicine in Needplans to develop stable cell dry powder vaccine formulations for efficient and noninvasive inhaled delivery. Furthermore, recent studies have demonstrated the effectiveness of porous particles and nanoparticles in efficiently delivering therapeutic aerosols with the potential for larger dose delivery,,. Besides pulmonary vaccine delivery, other methods of needleless immunizations in development include liquid-jet injection, epidermal powder immunization, and topical application (through cutaneous routes), and oral and nasal immunizations (through mucosal routes) have been proposed as alternatives to intravenous immunizations. Liquid-jet injections use the kinetic energy from a high velocity vaccine jet (typically up to 100 m/s, with a microneedle tip) to penetrate the skin and deliver the vaccine intradermally, subcutaneously, or intramuscularly. Targeting the skin promotes its contact with Langerhans cells, which initiate specific immune responses by processing and presenting antigen fragments to naïve T cells in the lymph nodes. Vaccines delivered by liquid-jet usually spread over a larger tissue area than vaccines administered with needles, and may allow more contact with antigen-presenting cells before being degraded. While many vaccines (e.g. influenza and hepatitis B) have been successfully delivered using liquid-jets, cross-contamination and cost are major limitations. The development of disposable-cartridge jet injectors and single-use, pre-filled disposable devices have sought to alleviate concerns about contamination. Epidermal powder immunizations facilitate storage of vaccine powders and there is strong clinical evidence for DNA vaccines; however, non-DNA vaccines have enjoyed little commercial success. Topical vaccine application, like liquid-jet and epidermal powder immunizations, naturally target Langerhans cells and are cheaper and easier to use (with high patient compliance); however, simple topical delivery yields an inadequate immune response due to the low permeability of the stratum corenum, the outer layer of the skin. Current research includes using topically applied adjuvants, colloidal carriers, and physical methods (such as microneedles, ultrasound, and electroporation) with topical application,.Oral vaccine delivery has been used for live attenuated pathogens, such as polio and typhoid, and is attractive because of its simplicity and ease of administration. However, vaccines are degraded and deactivated in the acidic gastrointestinal environment and high doses are required for adequate immune responses; improving response variability is an active area of research. Nasal delivery allows easier access to mucosal membranes than does oral delivery, but the short contact time and enzymatic activity (while less relative to that in gastrointestinal tract) poses considerable challenges which have yet to be overcome. A subset of oral vaccine delivery is temperature-stable formulations of vaccines expressed in transgenic organisms such as plants or crops,. Edible vaccines are attractive because they are easy to administer; they are also theoretically cheap to produce because no protein purification steps are needed. Studies on edible plant vaccines have shown to stimulate immunogenic responses against the hepatitis B virus and Norwalk virus (which causes diarrhea). They also have protective capacity against pathogens causing bacterial diarrhea (such as cholera and enterotoxigenic Escherichia coli), and tetanus toxin (produced by bacterium Clostridium tetani). The latter is a common childhood vaccination target along with diptheria and pertussis. Ongoing research aims to (1) understand variations in vaccine stability and immunogenicity in mucosal delivery, (2) express higher levels of antigen, (3) guard against degradation of protein components in the stomach and gut before they can elicit an immune response, and (4) understand the risks of genetic contamination of foodstuffs and the threats to biodiversity. Diagnostics – Microfluidic devices Another promising biotechnology is microfluidics for development of portable and cheap health diagnostics,. Microfluidics deals with the behavior and precise manipulation of small volumes of liquids and gases moving through microchannels embedded in a chip. Also known as “lab-on-a-chip”, microfluidic devices have the potential to automate complex laboratory tasks such as sample preparation, pre-concentration, and analyte detection (i.e. detection of desired biomarkers, such as antibodies against hepatitis B, conserved nucleic acid sequences in malaria parasites, T-cells for monitoring HIV/AIDS, etc.) on a chip. Usually, these laboratory tasks require bulky, mechanically complex, expensive, power-draining instruments, such as centrifuges (e.g. for sample preconcentration), vortexes and spinners (e.g. for mixing liquids), liquid-handling robots (e.g. for quantifying protein in benchtop immunoassays), thermocyclers (e.g. for amplifying nucleic acids), flow cytometers (e.g. for counting and sorting cells), and high-powered microscopes (e.g. for visualizing cells). A true “lab-on-a-chip” would allow health workers in developing countries to run common lab tests with greater accuracy and throughput without significant prior training (Figure 1). Furthermore, miniaturizing onto a battery-powered or even solar-powered handheld device would allow health workers to diagnose at point-of-care, reducing time spent waiting for results and the number of patient visits to the clinic (Figure 1A). The time saved is on the order of days in situations where samples need to be sent to national/regional testing centers for processing. Clinics with poor patient compliance in follow-up visits may particularly benefit because diagnosis and treatment prescriptions can be done on a single visit. Additionally, microfluidic diagnostic devices could be employed in a decentralized health care system where health workers travel to the village or rural home to deliver care.   Figure 1: Microfluidics: an emerging technology in portable, low-cost diagnostics. A: Proposed intervention of device in workflow. B: Ability of microfluidics to do multiple tests rapidly. Cells, metabolites, nucleic acids, and proteins can all be analyzed to give a complete diagnosis. Even in situations where the testing center has the capacity to run the desired assay, microfluidic diagnostics still save time by integrating multiple tasks and by processing microliter to nanoliter volumes. At these small volumes, reactions are rarely diffusion-limited, allowing for faster kinetics particularly when catalysts are involved, and thermal mass is minimized, allowing quicker responses to heat changes e.g. in thermocycling for PCR . The ability to process small volumes also allows for less invasive patient sampling procedures such as fingerpricks as compared to more invasive techniques such as intravenous blood draws (Figure 1A). Most studies to date have focused on particular microfluidic procedures such as fluid actuation, mixing, sample preparation, analyte detection, because each poses tremendous scientific and technical challenges and depends on the physical, chemical, and biological makeup of the analyte. With extensive work on new strategies and characterization, researchers are looking to integrate multiple procedures in order to be able to detect multiple analytes on a single chip (as illustrated in Figure 1B). Analytes are divided roughly into four classes: (1) cells, (2) metabolites, (3) nucleic acids, and (4) proteins . Each class of biomarker is described in terms of its importance in diagnosing infections and health conditions, and significant research advances relevant to the advancement of global health are identified. Cells Cell counts are important measures in addressing anemia and hematology via red blood cell and complete blood counts, as well as in monitoring HIV-infected patients for structuring antiretroviral treatment regimens via CD4+ T-cells. One study suggests that differential shear flows on antibody-functionalized surfaces can selectively capture CD4+ T-cells without labeling in a simple microfluidic format . Cell analysis via microscopic examination is important for parasitology (e.g. blood smears for malaria). Additionally, microbiological culture is important for determining drug-resistant strains of bacteria (e.g. tuberculosis, Staph A), because culture is still considered the “gold standard” relative to newer molecular-based techniques detecting nucleic acids. Small Molecules Detection of small molecules is important for monitoring blood chemistries. Common targets include bicarbonate for regulating pH, sodium and potassium for maintaining specific electrolyte levels in nerve and muscle function, oxygen and carbon dioxide for determining respiratory and/or metabolic problems, and glucose for metabolic disorders such as diabetes. Vitamins and minerals are also relevant targets for detection, as they allow for the diagnosis and monitoring of nutritional deficiencies. Popular techniques include electrochemical detection using thin-film patterned electrodes. iSTAT, a current commercial product produced by Abbot Diagnostics, employs this specific technique. Nucleic Acids Conserved DNA or viral RNA sequences are often targets for detecting specific infectious diseases and for determining the stage of a disease (e.g. HIV RNA viral load). Genotyping is also common for distinguishing between pathogen strains (e.g. Hepatitis C). The most popular techniques are PCR and RT-PCR, due to their intrinsic specificity and signal amplification. Certain technical challenges include the need for sample pre-treatment of lysed cells and low-cost methods for portable signal amplification and detection. One study demonstrates that oligonucleotide-conjugated nanoparticle probes coupled with silver reduction amplification can yield a low-cost and sensitive system. Proteins Antibody and antigen markers can indicate infections predominant in developing countries (such as anti-HIV antibodies, gp41 and gp120 antigens for HIV). One study uses a gold-silver sandwich immunoassay for detecting αHIV-1 antibodies in a microfluidic setup. The opacity of the solution due to silver reduction correlated with the amount of antibody in patient serum and was read by a simple, low-cost absorbance reader. Cost-reduction is perhaps the most attractive quality of microfluidic diagnostic devices. Typically, one-time purchases of fixed instruments range from tens to hundreds of thousands of US dollars. For example, the cost of reagents is $5 for immunoassays and $50-300 for nucleic acid tests in a typical in-house hospital laboratory in the developed world. In contrast, microfluidic devices in the developing world would need fixed instrument costs at tens of dollars, and per-assay costs on the order of pennies, which would include both chips and reagents. By scaling down reagent volumes hundred- to thousand-fold and by using cheaper materials, such as injection-moulded plastics instead of glass, quartz, and silicon, and electrical components (Figure 1A), the costs associated to fixed instrument and assay are reasonable for device deployment in limited-resource settings. Implementing an appropriate intervention of microfluidic diagnostics, or of any new technology, in the health networks of developing countries is far from trivial. Figure 1A illustrates some of the considerations for a lab-on-a-chip both in and out of the clinic. For instance, it is necessary to minimize the number of moving parts needed on the chip and in the reader in order to design an easily operated device. Also, a minimal user interface consisting of a few buttons for powering and operation, and signal lights for showing status of test, on the reader itself may make the device easier for an untrained health worker to operate. Considerations downstream of the microfluidic assay include recording, storing, and communicating results (Figure 1A). Typically, most centralized testing sites and practically all rural testing sites rely solely on written records, but digital records could improve quality of care (by assuring evidence-based medicine) and expedite communication, particularly in disease surveillance, where communication of results between clinics is vital . Results that are typed, synced via USB storage key, or uploaded via wireless transmission to a computer can then be collected and stored locally on a clinic-level network database. Periodically, local networks of electronic records can communicate periodically with other clinics through syncing or internet upload. D-Tree International, a non-governmental organization dedicated to improving medical records management in developing countries, plans to train and equip frontline providers with personal digital assistants, smart cards, and back up systems for sending data in real-time. This non-profit organization also develops evidence-based, standardized diagnostic and treatment protocols customized for local cultural conditions such as language, epidemiological patterns, and drug lists, also taking into account resources by calculating drug dosage based on patient statistics. Technology is one part of the solution and must be designed appropriately to its settings (Figure 2). For example, backup batteries and dust covers (Figure 2A) are common in many regional and rural testing centers. This highlights performance and design considerations in alternative power, using backup batteries which may be rechargeable or even solar-powered, and dusty environments. Bench-top units are fine in centralized testing centers but cannot be transported to rural sites. Flow cytometers (Figure 2B) are bulky and expensive, complicated to use, and are often in English instead of native languages. It is also clear that many diagnostic tests require significant training and are inadequate due to their lack of specificity. For instance, malaria blood smears are widely performed, and yet are difficult to read due to the subtle differences in phenotype between erythrocytes infected with different Plasmodium species. One alternative to microscopes and blood smears may be detecting differences in cell deformability, or electrical properties by using microfluidic setups ,.   Figure 2. Design constraints depend on circumstances in the developing world (pictures of labs). A: Lab at Kicukiro (outside Kigali, Rwanda) relies on backup batteries and dust covers. B: Flow cytometer at Gisenyi (regional test center in Rwanda) is bulky, expensive, difficult to easy, and does not read in local language (English instead of French or Kinyarwanda). C: Malaria blood smears are commonplace yet difficult to read, requiring trained personnel. Conclusions There is a need for scientific innovation in global health, and the identification of key emerging technologies in diagnosis and prevention are the first steps. Technologies need to be relevant to local conditions, and developing countries have a unique set of challenges that advances in biotechnology need to address before they become valuable as innovations. The need for biotechnologies that can be compatible to a decentralized, prevention-based health paradigm is evident because a conventional health system is unsustainable and incompatible with a developing nation’s budget, environment, and demographics. Beyond identifying key biotechnologies, their development goes hand in hand with other efforts for improving health infrastructures. Training programs are critical for improving skills of health workers, particularly in rural areas, and new technologies intended to work in these circumstances need to be introduced and involved at an early stage. Faster and reliable communication and data storage systems will improve epidemiological surveillance and allow health workers to better customize diagnoses and treatments based on statistics pertinent to specific patients, as well as the local population as a whole. Health education and awareness programs are important cost-effective interventions for stressing disease prevention and healthy lifestyles, and new technologies need to be understood by the populations they serve, in terms of access, changes in healthcare, and the potential positive and negative health side effects. A multidisciplinary approach with biotechnology is important for sustained and comprehensive improvements in health infrastructures and quality of care in developing countries. Acknowledgement I thank Samuel Sia for his research mentorship, Eileen Sun for helpful comments on manuscript, and the Frank H. Buck Foundation for financial support in graduate studies. Curtis Chin is a PhD student in the Department of Biomedical Engineering at Columbia University. His research interests include microtechnologies for global health diagnostics and tissue engineering. He obtained his BS in Chemical Engineering from the Massachusetts Institute of Technology. Notes UNDP, Human Development Report 2001: Making New Technologies Work for Human Development. 2001, United Nations Development Programme: New York. Chin, C.D., V. Linder, and S.K. Sia, Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip, 2007. 7(1): p. 41-57. Alwan, A. and B. Modell, Recommendations for introducing genetics services in developing countries. Nat Rev Genet, 2003. 4(1): p. 61-8. Recombinant vaccines are created by genetically modifying microorganisms such as bacteria and yeast and stimulating them to produce large quantities of immunogenic proteins. Daar, A.S., et al., Top ten biotechnologies for improving health in developing countries. Nat Genet, 2002. 32(2): p. 229-32. Mitragotri, S., Immunization without needles. Nat Rev Immunol, 2005. 5(12): p. 905-16. BCG vaccine is against tuberculosis which is prepared from a strain of the attenuated live bovine tuberculosis bacillus. Freeze-drying (also known as lyophilization) is a common dehydration process used to preserve a sensitive material and make transport convenient. Freeze-drying involves a two-step process: 1) freezing below the lowest temperature at which solid and liquid phases can coexist (eutectic point), and 2) sublimination of ice crystals to water vapor. Wong, Y.L., et al., Drying a tuberculosis vaccine without freezing. Proc Natl Acad Sci U S A, 2007. 104(8): p. 2591-5. Millqvist-Fureby, A., M. Malmsten, and B. Bergenstahl, An aqueous polymer two-phase system as carrier in the spray-drying of biological material. Journal of Colloid and Interface Science, 2000. 225(1): p. 54-61. Vanbever, R., et al., Formulation and physical characterization of large porous particles for inhalation. Pharm Res, 1999. 16(11): p. 1735-42. Medicine in Need is a non-governmental organization founded by David Edwards, the principal investigator of the aforementioned study. Edwards, D.A., et al., Large porous particles for pulmonary drug delivery. Science, 1997. 276(5320): p. 1868-71. Pulliam, B., J.C. Sung, and D.A. Edwards, Design of nanoparticle-based dry powder pulmonary vaccines. Expert Opin Drug Deliv, 2007. 4(6): p. 651-663. Tsapis, N., et al., Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci U S A, 2002. 99(19): p. 12001-5. An adjuvant is an agent that is mixed with an antigen and increases the immune response to that antigen following immunization6 A colloidal carrier is a stable system of small particles of lipds, polymers or any other material that encapsulate a vaccine6 Guy, B., The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol, 2007. 5(7): p. 505 Acharya, T., A.S. Daar, and P.A. Singer, Biotechnology and the UN’s Millennium Development Goals. Nat Biotechnol, 2003. 21(12): p. 1434-6. Acharya, T., et al., Strengthening the role of genomics in global health. PLoS Med, 2004. 1(3): p. e40. Mason, H.S., et al., Edible plant vaccines: applications for prophylactic and therapeutic molecular medicine. Trends Mol Med, 2002. 8(7): p. 324-9. Daniell, H., S.J. Streatfield, and K. Wycoff, Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci, 2001. 6(5): p. 219-26. Tregoning, J.S., et al., Protection against tetanus toxin using a plant-based vaccine. Eur J Immunol, 2005. 35(4): p. 1320-6. Yager, P., et al., Microfluidic diagnostic technologies for global public health. Nature, 2006. 442(7101): p. 412-8. The quality, conditions, and types of tests performed at health centers usually correlates with degree of urban development2. PCR, or polymerase chain reaction, is a technique used for detection of nucleic acids (PCR for DNA, RT-PCR for RNA), typically for determining infection and pathogen strain or subtype identification. A section of target DNA is marked off with flanking DNA primers and amplified exponentially with repeated heating and cooling patterns (thermocycles). For a more detailed discussion on microfluidic diagnostic technologies for global health, see references 8 and 21. Cheng, X., et al., A microfluidic device for practical label-free CD4(+) T cell counting of HIV-infected subjects. Lab Chip, 2007. 7(2): p. 170-8. Taton, T.A., C.A. Mirkin, and R.L. Letsinger, Scanometric DNA array detection with nanoparticle probes. Science, 2000. 289(5485): p. 1757-1760. Sia, S.K., et al., An integrated approach to a portable and low-cost immunoassay for resource-poor settings. Angew Chem Int Ed Engl, 2004. 43(4): p. 498-502. Fixed instrument consists of hardware components for analyte detection, fluid actuation, power, and electronics for signal enhancement, user interfacing, and data tranmission. Assay components include chips (which can be reused depending on the material and application) and reagents. Initiatives such as One Laptop Per Child (headed by John Negroponte, head of MIT’s Media Lab) may also help close the digital divide. Shelby, J.P., et al., A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes. Proc Natl Acad Sci U S A, 2003. 100(25): p. 14618-22. Gascoyne, P., J. Satayavivad, and M. Ruchirawat, Microfluidic approaches to malaria detection. Acta Tropica, 2004. 89(3): p. 357-369. References Acharya, T., et al., Strengthening the role of genomics in global health. PLoS Med, 2004. 1(3): p. e40. Acharya, T., A.S. Daar, and P.A. Singer, Biotechnology and the UN’s Millennium Development Goals. Nat Biotechnol, 2003. 21(12): p. 1434-6. Alwan, A. and B. Modell, Recommendations for introducing genetics services in developing countries. Nat Rev Genet, 2003. 4(1): p. 61-8. Cheng, X., et al., A microfluidic device for practical label-free CD4(+) T cell counting of HIV-infected subjects. Lab Chip, 2007. 7(2): p. 170-8. Chin, C.D., V. Linder, and S.K. Sia, Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip, 2007. 7(1): p. 41-57. Daniell, H., S.J. Streatfield, and K. Wycoff, Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci, 2001. 6(5): p. 219-26. Daar, A.S., et al., Top ten biotechnologies for improving health in developing countries. Nat Genet, 2002. 32(2): p. 229-32. Edwards, D.A., et al., Large porous particles for pulmonary drug delivery. Science, 1997. 276(5320): p. 1868-71. Gascoyne, P., J. Satayavivad, and M. Ruchirawat, Microfluidic approaches to malaria detection. Acta Tropica, 2004. 89(3): p. 357-369. Guy, B., The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol, 2007. 5(7): p. 505 Mason, H.S., et al., Edible plant vaccines: applications for prophylactic and therapeutic molecular medicine. Trends Mol Med, 2002. 8(7): p. 324-9. Millqvist-Fureby, A., M. Malmsten, and B. Bergenstahl, An aqueous polymer two-phase system as carrier in the spray-drying of biological material. Journal of Colloid and Interface Science, 2000. 225(1): p. 54-61. Mitragotri, S., Immunization without needles. Nat Rev Immunol, 2005. 5(12): p. 905-16. Pulliam, B., J.C. Sung, and D.A. Edwards, Design of nanoparticle-based dry powder pulmonary vaccines. Expert Opin Drug Deliv, 2007. 4(6): p. 651-663. Shelby, J.P., et al., A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes. Proc Natl Acad Sci U S A, 2003. 100(25): p. 14618-22. Sia, S.K., et al., An integrated approach to a portable and low-cost immunoassay for resource-poor settings. Angew Chem Int Ed Engl, 2004. 43(4): p. 498-502. Taton, T.A., C.A. Mirkin, and R.L. Letsinger, Scanometric DNA array detection with nanoparticle probes. Science, 2000. 289(5485): p. 1757-1760. Tregoning, J.S., et al., Protection against tetanus toxin using a plant-based vaccine. Eur J Immunol, 2005. 35(4): p. 1320-6. Tsapis, N., et al., Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci U S A, 2002. 99(19): p. 12001-5. UNDP, Human Development Report 2001: Making New Technologies Work for Human Development. 2001, United Nations Development Programme: New York. Vanbever, R., et al., Formulation and physical characterization of large porous particles for inhalation. Pharm Res, 1999. 16(11): p. 1735-42. Wong, Y.L., et al., Drying a tuberculosis vaccine without freezing. Proc Natl Acad Sci U S A, 2007. 104(8): p. 2591-5. Yager, P., et al., Microfluidic diagnostic technologies for global public health. Nature, 2006. 442(7101): p. 412-8. Acknowledgements I thank Samuel Sia for his research mentorship, Eileen Sun for helpful comments on manuscript, and the Frank H. Buck Foundation for financial support in graduate studies.This work is licensed under a CC-BY-NC-ND license.  
 
Publisher Consilience - The Journal of Sustainable Development
 
Date 2009-05-12
 
Type info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
 
Format application/pdf
 
Identifier http://www.consiliencejournal.org/index.php/consilience/article/view/4
 
Source Consilience - The Journal of Sustainable Development; 2009: Issue One
 
Language eng
 
Relation http://www.consiliencejournal.org/index.php/consilience/article/view/4/3