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Effective management of diabetes largely benefits from early diagnosis followed by intensive long-term regulation of blood glucose. The levels of glycohemoglobin (HbA1 and HbA1c) have been used as standard biomarkers to assess long-term blood glucose concentrations for diabetes diagnosis and management. Gold standard laboratory methods for HbA1 and HbA1c testing are often costly and not widely available. Moreover, currently available point-of-care (POC) immunoassay-based glycohemoglobin tests may produce inaccurate test results for patient with co-existing diseases such as hemoglobin disorders and anemia. Here, we report a POC platform, HemeChip-GHb, for quantitative HbA1 detection leveraging paper-based affinity electrophoresis.We describe the design and development of the HemeChip-GHb test. Feasibility and accuracy of the HemeChip-GHb system were demonstrated by testing blood samples collected from healthy donors, patients with prediabetes, and patients with diabetes.HbA1 levels measured with HemeChip-GHb show 0.96 correlation to the levels reported from the clinical standard HPLC tests, and with a bias of -0.72% based on Bland-Altman analysis. 99.6% of the HbA1 levels for paired HemeChip-GHb and HPLC fell within A and B zones of no difference in clinical outcome based on error grid analysis.Using HemeChip-GHb we achieved accurate diabetes status detection with sensitivity and specificity of 100%.We presented a novel POC paper-based affinity electrophoresis platform that has the potential for accurately diagnosing diabetes, and addressing an unmet need for accurate and affordable diagnostics in resource-challenged environments.

Hydrogen sensing is important in many industrial, biomedical, environmental, and energy applications. Realizing a practical, reliable, and inexpensive hydrogen sensor, however, is an ongoing challe...

Hydrogen (H2) sensing is crucial in a wide variety of areas, such as industrial, environmental, energy and biomedical applications. However, engineering a practical, reliable, fast, sensitive and cost-effective hydrogen sensor is a persistent challenge. Here we demonstrate hydrogen sensing using aluminumdoped zinc oxide (AZO) metasurfaces based on optical read-out. The proposed sensing system consists of highly ordered AZO nanotubes (hollow pillars) standing on a SiO2 layer deposited on a Si wafer. Upon exposure to hydrogen gas, the AZO nanotube system shows a wavelength shift in the minimum reflectance by ∼13 nm within 10 minutes for a hydrogen concentration of 4%. These AZO nanotubes can also sense the presence of a low concentration (0.7%) of hydrogen gas within 10 minutes. Their rapid response time even for a low concentration, the possibility of large sensing area fabrication with good precision, and high sensitivity at room temperature make these highly ordered nanotube structures a promising miniaturized H2 gas sensor.

Nearly 7% of the world’s population lives with a hemoglobin variant. Hemoglobins S, C, and E are the most common and significant hemoglobin variants worldwide. Sickle cell disease, caused by hemoglobin S, is highly prevalent in sub-Saharan Africa and in tribal populations of Central India. Hemoglobin C is common in West Africa, and hemoglobin E is common in Southeast Asia. Screening for significant hemoglobin disorders is not currently feasible in many low-income countries with the high disease burden. Lack of early diagnosis leads to preventable high morbidity and mortality in children born with hemoglobin variants in low-resource settings. Here, we describe HemeChip, the first miniaturized, paper-based, microchip electrophoresis platform for identifying the most common hemoglobin variants easily and affordably at the point-of-care in low-resource settings. HemeChip test works with a drop of blood. HemeChip system guides the user step-by-step through the test procedure with animated on-screen instructions. Hemoglobin identification and quantification is automatically performed, and hemoglobin types and percentages are displayed in an easily understandable, objective way. We show the feasibility and high accuracy of HemeChip via testing 768 subjects by clinical sites in the United States, Central India, sub-Saharan Africa, and Southeast Asia. Validation studies include hemoglobin E testing in Bangkok, Thailand, and hemoglobin S testing in Chhattisgarh, India, and in Kano, Nigeria, where the sickle cell disease burden is the highest in the world. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. Study design, methods, and results are presented according to the Standards for Reporting Diagnostic Accuracy (STARD). HemeChip correctly identified all subjects with hemoglobin S, C, and E variants with 100% sensitivity, and displayed an overall diagnostic accuracy of 98.4% in comparison to reference standard methods. HemeChip is a versatile, mass-producible microchip electrophoresis platform that addresses a major unmet need of decentralized hemoglobin analysis in resource-limited settings.

We demonstrate optical hydrogen sensing using metasurfaces based on aluminum-doped zinc oxide (AZO) nanotubes. The sensing system shows 2-13 nm of resonance wavelength shift upon exposure to hydrogen gas of concentration 0.7-4.0 % within 10 minutes.

In this work, we demonstrate a novel low-cost, self-powered paper-based biosensor for glucose monitoring. The device operating mechanism is based on a glucose/oxygen enzymatic fuel cell using an electrochemical energy conversion as a transducing element for glucose monitoring. The self-powered glucose biosensor features (i) a 3D origami paper-based structure for easy system integration onto paper, (ii) an air-cathode on paper for low-cost production and easy operation, and (iii) a screen printed chitosan/glucose oxidase anode for stable current generation as an analytical signal for glucose monitoring. The sensor showed a linear range of output current at 1–5 mM glucose (R2=0.996) with a sensitivity of 0.02 µA mM−1. The advantages offered by such a device, including a low cost, lack of external power sources/sophisticated external transducers, and the capacity to rapidly generate reliable results, are well suited for the clinical and social settings of the developing world.

This work describes the development and operation of a microliter-sized microbial fuel cell-based biosensor for monitoring toxic substances in water. The biosensor features the integration of (i) a three-electrode configuration to provide electrochemical sensing functionality for improving sensitivity and reliability in water quality testing and (ii) an air-bubble trap to prevent all unwanted bubbles from entering the sensing surface for maximizing bacterial growth and their subsequent electron transfer. The miniaturization of the biosensor produced favorable conditions for (i) reducing measurement time with high probability of cell attachment/biofilm formation in the micro-sized chamber and (ii) enhancing the reaction sensitivity with large surface area-to-volume ratio and increased reaction kinetics. When formaldehyde was introduced as a toxic component, the rapid and sensitive current responses were obtained over a concentration range from 0.001% to 0.1% in the biosensor with 0.2 V (versus solid-state thin film Ag/AgCl reference electrode) applied on the anode.

HemeChip is the first miniaturized, single-use cartridge-based microchip electrophoresis system for identifying and quantifying hemoglobin (Hb) variants from a drop of blood at the point-of-care (POC). It is estimated that 7% of world's population lives with a hemoglobin variant, and one of the most common and severe one being the recessively transmitted sickle hemoglobin which results in Sickle Cell Disease (SCD). HemeChip (Fig. 1A,C) separates Hb variants on a strip of cellulose acetate (CA) paper that is housed in the HemeChip cartridge. This HemeChip cartridge is a mass-producible, single-use cartridge that maintains a controlled environment and a constant electric field (applied through the electrodes, Fig. 1B) for the Hb separation process. The cartridge also contains an in-chip blotting mechanism and an anti-fogging feature. The anti-fogging feature is essential for real-time imaging and tracking of Hb band(s) during the separation process. HemeChip is integrated with a portable reader (Fig. 1D) to detect the type(s) and fraction of hemoglobin types present in a blood sample. HemeChip technology has been designed and developed to offer a robust, user-friendly platform to detect, identify, and quantify Hb variants (responsible for SCD variants) even in a limited resource settings.

Sickle Cell Disease (SCD) is a genetically inherited hemoglobin disorder, which can be fatal if left undiagnosed and untreated. Geographically, the most SCD-prevalent regions have the lowest gross domestic product (GDP) and are therefore unable to implement costly, centralized SCD screening programs. In these regions, the early mortality is 50%–90% among children born with sickle cell anemia [1]. According to the World Health Organization (WHO), who passed a resolution naming SCD as a global public health problem in 2006 [2], 70% of these early mortality could be prevented by implementing low-cost SCD screening followed by cost-effective treatments [3]. To address this need, we developed HemeChip, a mass-producible, low-cost, microchip version of electrophoresis, able to detect and quantify hemoglobin type(s) from whole blood at the point of care (POC). The process is fast (

In this paper, we report a multianode paper-based microbial fuel cell (MFC) capable of generating a power density of 28.4 μW/cm 2 . This MFC features: 1) flexible multilayered carbon cloth anodes for bacterial attachment and 2) paper reservoirs for holding the anolyte and catholyte for an extended period of time. The hydrophobic barriers in the anodes and paper-based reservoirs were patterned by impregnating and selectively polymerizing photoresist through UV lithography. Upon inoculum/catholyte introduction, a current of 211 μA/cm 2 was immediately generated. By using the multianode MFC, the power and current densities increased by 5× and 3×, respectively, compared with a single anode one. The paper-based MFC is expected to be a simple and easy-to-use power source for single-use diagnostic biosensors because even sewage or soiled water in a puddle can become an excellent source for operating MFCs and harvesting electricity through bacterial metabolism.

Microbial fuel cells (MFCs) are an alternative electricity generating technology and efficient method for removing organic material from wastewater. Their low power densities, however, hinder practical applications. A primary limitation in these systems is the anode. The chemical makeup and surface area of the anode influences bacterial respiration rates and in turn, electricity generation. Some of the highest power densities have been reported using large surface area anodes, but due to variable chemical/physical factors (e.g., solution chemistry, architecture) among these studies, meaningful comparisons are difficult to make. In this work, we compare under identical conditions six micro/nano-structured anodes in micro-sized MFCs (47 μL). The six materials investigated include carbon nanotube (CNT), carbon nanofiber (CNF), gold/poly (ϵ-caprolactone) microfiber (GPM), gold/poly(ϵ-caprolactone) nanofiber (GPN), planar gold (PG), and conventional carbon paper (CP). The MFCs using three dimensional anode structures (CNT, CNF, GPM, and GPN) exhibited lower internal resistances than the macroscopic CP and two-dimensional PG anodes. However, those novel anode materials suffered from major issues such as high activation loss and instability for long-term operation, causing an enduring problem in creating widespread commercial MFC applications. The reported work provides an in-depth understanding of the interplay between micro-/nano-structured anodes and active microbial biofilm, suggesting future directions of those novel anode materials for MFC technologies.

There is an extensively growing interest in using paper or paper-like substrates for batteries and other energy storage devices. Due to their intrinsic characteristics, paper (or paper-like) batteries show outstanding performance while retaining low cost, multifunctionality, versatility, flexibility and disposability. In this overview, we review recent achievements in paper (or paper-like) batteries as well as their applications. Various types of paper power devices are discussed including electrochemical batteries, biofuel cells, lithium-ion batteries, supercapacitors, and nanogenerators. Further scientific and technological challenges in this field are also discussed.

THIS ARTICLE FOCUSES ON a ?microsized microbial solar cell (MSC) that can produce sustainable energy through photosynthetic reactions of cyanobacteria Synechocystis PCC 6803 in the anode. The MSC has 57-?L anode/cathode chambers defined by laser-machined poly(methyl methacrylate) (PMMA) substrates. We obtained a maximum power density of 7.09 nW/cm2, which is 170 times more power than previously reported microelectromechanical system (MEMS) MSCs. The importance of the light intensity was demonstrated by the higher values of generated current during the day than at night, indicating light-dependent photosynthetic processes. Considering that sunlight offers an ?unlimited source of energy, the development of self-sustainable MSCs that rely on light as an energy source will become an increasingly important area of research in the future. In accordance with the MSC, we developed a photosynthetic cathode-based microbial fuel cell (MFC), showing that the use of cyanobacteria can be useful as well as efficient and sustainable catalysts for the cathode since they act as oxygenators.

Introduction: Nearly 24% of the world's population carry hemoglobin (Hb) gene variants, with the large majority of affected births occurring in low-income countries. The most prevalent structural Hb variants are the recessive β-globin gene mutations, βS or S, βC or C, and βE or E1. Hb S mutation is prevalent in sub-Saharan Africa and in Central India. Hb C is common in West Africa, and Hb E is common in Southeast Asia and in India. Homozygotes or compound heterozygotes with βS (e.g., Hb SS or SC) have sickle cell disease (SCD), a chronic sickling disorder associated with pain, chronic multi-organ damage, and high mortality. While Hb EE causes only a mild microcytic anemia, Hb E in combination with β-thalassemia can lead to transfusion dependent thalassemia. Though carriers are typically asymptomatic, they may pass the mutations to their offspring. Screening is needed so that these disorders can be diagnosed early and managed in a timely manner2. For example, in low-income countries, due to lack of nationwide screening and comprehensive care programs, up to 80% of babies born with SCD are undiagnosed and less than half of them survive beyond 5 years of age2. The unmet need for affordable, portable, accurate point-of-care tests to facilitate decentralized hemoglobin testing in resource-constrained countries is well-recognized 2,3. Here, we present international multi-site clinical validation results and high diagnostic accuracy of the 'HemeChip' (Fig. 1), an affordable, 10-minute point-of-care microchip electrophoresis test for identifying common Hb variants S, C, and E. Methods: Institutional Review Board approvals were obtained at each study site, and blood samples were collected as part of the standard clinical care. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. 315 children (6 weeks to 5 years of age) were tested in Kano, Nigeria. Study participants were enrolled at three hospitals, Amino Kano Teaching Hospital, Murtala Mohammed Specialist Hospital, and Hasiya Bayero Pediatric Hospital. 124 subjects (7 weeks to 63 years old) were included in the study at Siriraj Thalassemia Center in Bangkok, Thailand. 298 subjects (8 months to 65 years old) were tested at a referral testing facility of ICMR-National Institute of Research in Tribal Health, located at Late Baliram Kashayap Memorial Medical College, Jagdalpur, Chhattisgarh, India. Blood samples were tested with both HemeChip and the standard reference methods, high performance liquid chromatography or cellulose acetate electrophoresis. Reference test results were not available to the HemeChip users. Similarly, HemeChip test results were not available to the users of the standard reference tests. Clinical validation studies presented here were performed with a fully functional, portable HemeChip prototype developed at Case Western Reserve University (Fig. 1A). A commercial product has been developed based on this technology by Hemex Health Inc. under the product name, GazelleTM(Fig. 1B). Results and Discussion: Among the total 768 tests performed with HemeChip in all test sites, 732 were valid tests, as defined by the Standards for Reporting Diagnostic Accuracy (STARD)4. HemeChip correctly identified all subjects with Hb SS, Hb SC, Hb AS, Hb AE, and Hb EE with 100% accuracy (Table 1). Nine subjects with normal Hb (Hb AA) were identified as HbSS in Nigeria. No subjects with disease were identified as normal or trait by HemeChip. Three subjects with compound heterozygous Hb Sβ-thalassemia (2 subjects with Hb Sβ+-thalassemia, 1 subject with Hb Sβ0-thalassemia) were identified as Hb SS. Sensitivity was 100% for all Hb types tested. Specificity was 98.7% for Hb SS versus other Hb types, and 100% for all other Hb types tested. HemeChip displayed an overall diagnostic accuracy of 98.4% in comparison to standard reference methods for the Hb variants tested in all clinical testing sites (Table 1). HemeChip is a versatile point-of-care system that enables affordable, accurate, decentralized hemoglobin testing in resource-limited settings. References: 1. Weatherall DJ, Clegg JB. Bull World Health Organ. 2001;79(8):704-712. 2. Mburu J, Odame I. International Journal of Laboratory Hematology. 2019;41(S1):82-88. 3. Alapan Y, Fraiwan A, Kucukal E, et al. Expert Review of Medical Devices. 2016;13(12):1073-1093. 4. Bossuyt PM, Reitsma JB, Bruns DE, et al. BMJ : British Medical Journal. 2015;351:h5527. Disclosures Fraiwan: Hemex Health, Inc.: Equity Ownership, Patents & Royalties. Hasan:Hemex Health, Inc.: Equity Ownership, Patents & Royalties. An:Hemex Health, Inc.: Patents & Royalties. Thota:Hemex Health, Inc.: Employment. Piccone:Hemex Health, Inc.: Patents & Royalties. Little:Hemex Health, Inc.: Patents & Royalties; GBT: Research Funding. Gurkan:Hemex Health, Inc.: Consultancy, Employment, Equity Ownership, Patents & Royalties, Research Funding.

Nigeria leads the world in the number of cases of sickle cell disease (SCD). An estimated 150,000 babies are born annually in Nigeria with SCD, a heredity disorder, and 70-90% die before age 5. Only a small portion of affected infants and children in sub Saharan Africa (SSA) reach adolescence. Over 650 children die per day in sub-Saharan Africa from SCD. These dismal statistics are in sharp contrast to outcomes in high-income countries (HICs) where more than 90% of SCD patients reach adulthood. The World Health Organization (WHO) estimates that 70% of deaths could be prevented with a low cost diagnostic and treatment plan. Meaningful preventive care and treatment cannot be implemented without a structured plan for early diagnosis and patient tracking.Early diagnosis requires improved access to parents and guardians of children with SCD, and gaining this access remains a challenge in most of SSA. In 2015, Nigeria's Kano state government, with support from foreign partners, established a community-based program for newborn registration. This platform provides unique access to newborn babies in one of Nigeria's most populous cities, but still lacks a functioning patient testing, tracking, and monitoring system, which we plan to address in our ongoing study. This study will introduce mobile health in a low-income country with low literacy rate and hopefully accustom that segment of the population to more varied mobile health applications that will ultimately improve their health in the long run. Our current operational platform in Kano, Nigeria provides access to a large population with a high prevalence of SCD. We have previously completed pilot testing of 315 subjects for SCD using our microchip electrophoresis test. We are planning to test up to 4,500 additional subjects less than 5 years of age at Murtala Muhammed Specialist Hospital. The hospital staff includes 97 physicians and 415 nurses and outpatient clinics serve about 30,000 patients monthly. The maternity department has a 200-bed capacity and the antenatal clinic performs about 1,000 deliveries and serves an average of 3,000 mothers monthly. Enrollment is planned to start on September 15, 2019 and medical staff are currently being trained to run the tests. Our study is registered in the United States National Library of Medicine's ClinicalTrials.gov (Identifier: NCT03948516). Our technology is uniquely paired with an automatic reader and an Electronic Medical Record (EMR) and patient management solution to record POC test results, register new cases, and track patients for follow-up (Fig. 1). The reader enables automated interpretation of test results, local and remote test data storage, and includes geolocation (Global Positioning System) (Fig. 2). The system will generate reports for all cases of SCD, track hospital visits, appointments, lab tests, and will have mobile and dashboard applications for tracking patients and samples. The application will be installed on mobile devices provided to users. The proposed system will be compliant with the existing privacy standards to handle medical data (e.g., HIPAA in the US and GDPR in the EU). All communications between the parties will be secured via end-to-end encryption as a safeguard. We anticipate that our project will increase the rates of screening, diagnosis and timely treatment of SCD in Kano State of Nigeria. The project's broader impact will likely be the ability to track and monitor screening, disease detection, diagnosis and treatment, which can be scaled up to the whole nation of Nigeria, then to sub-Saharan Africa. The data obtained and analyzed will be the first of their kind and will be used to inform the design of programs to improve access to, and availability of, effective care for this underserved populations. The importance of increased access to diagnosis and treatment should not be underestimated - it is crucial for realizing effective management of people with SCD. The impact can be enhanced by complementing diagnosis and patient tracking with education for the families so they can provide or seek the necessary preventative treatment. Identification of the location of the patients in need would help identify the areas where family, parent, caregiver education should be provided. Disclosures Fraiwan: Hemex Health, Inc.: Equity Ownership, Patents & Royalties. Hasan:Hemex Health, Inc.: Equity Ownership, Patents & Royalties. An:Hemex Health, Inc.: Patents & Royalties. Thota:Hemex Health, Inc.: Employment. Gurkan:Hemex Health, Inc.: Consultancy, Employment, Equity Ownership, Patents & Royalties, Research Funding.

Paper-based devices have recently emerged as simple and low-cost paradigms for fluid manipulation and analytical/clinical testing. However, there are significant challenges in developing paper-based devices at the system level, which contain integrated paper-based power sources. Here, we report a microfabricated paper-based bacteria-powered battery that is capable of generating power from microbial metabolism. The battery on paper showed a very short start-up time relative to conventional microbial fuel cells (MFCs); paper substrates eliminated the time traditional MFCs required to accumulate and acclimate bacteria on the anode. Only four batteries connected in series provided desired values of current and potential to power an LED for more than 30 minutes. The battery featured (i) a low-cost paper-based proton exchange membrane directly patterned on commercially available parchment paper and (ii) paper reservoirs for holding the anolyte and the catholyte for an extended period of time. Based on this concept, we also demonstrate the use of paper-based test platforms for the rapid characterization of electricity-generating bacteria. This paper-based microbial screening tool does not require external pumps/tubings and represents the most rapid test platform (

We present a microfabricated paper-based microbial fuel cell (MFC) generating a maximum power of 5.5 μW/cm(2). The MFC features (1) a paper-based proton exchange membrane by infiltrating sulfonated sodium polystyrene sulfonate and (2) micro-fabricated paper chambers by patterning hydrophobic barriers of photoresist. Once inoculum and catholyte were added to the MFC, a current of 74 μA was generated immediately. This paper-based MFC has the advantages of ease of use, low production cost, and high portability. The voltage produced was increased by 1.9 × when two MFC devices were stacked in series, while operating lifetime was significantly enhanced in parallel.

In this work, a microfabricated anode based on gold coated poly(ϵ-caprolactone) fiber was developed that outperformed gold microelectrode by a factor of 2.65-fold and even carbon paper by 1.39-fold. This is a result of its ability to three-dimensionally interface with bacterial biofilm, the metabolic “engines” of the microbial fuel cell (MFC). We also examined unavoidable issues as the MFC is significantly reduced in size (e.g. to the microscale); (1) bubble production or movement into the microchamber and (2) high sensitivity to flow rate variations. In fact, intentionally induced bubble generation in the anodic chamber reduced the MFC current density by 33% and the MFC required 4 days to recover its initial performance. Under different flow rates in the anode chamber, the current densities were almost constant, however, the current increased up to 38% with increasing flow rate in the cathode.

Sickle Cell Disease (SCD) affects 100,000 Americans and more than 14 million people globally, mostly in economically disadvantaged populations, and requires early diagnosis after birth and constant monitoring throughout the life-span of the patient. Areas covered: Early diagnosis of SCD still remains a challenge in preventing childhood mortality in the developing world due to requirements of skilled personnel and high-cost of currently available modalities. On the other hand, SCD monitoring presents insurmountable challenges due to heterogeneities among patient populations, as well as in the same individual longitudinally. Here, we describe emerging point-of-care micro/nano platform technologies for SCD screening and monitoring, and critically discuss current state of the art, potential challenges associated with these technologies, and future directions. Expert commentary: Recently developed microtechnologies offer simple, rapid, and affordable screening of SCD and have the potential to facilitate universal screening in resource-limited settings and developing countries. On the other hand, monitoring of SCD is more complicated compared to diagnosis and requires comprehensive validation of efficacy. Early use of novel microdevices for patient monitoring might come in especially handy in new clinical trial designs of emerging therapies.

Volatile organic compound (VOC) detection is critical for controlling industrial and commercial emissions, environmental monitoring, and public health. Simple, portable, rapid and low-cost VOC sensing platforms offer the benefits of on-site and real-time monitoring anytime and anywhere. The best and most practically useful approaches to monitoring would include equipment-free and power-free detection by the naked eye. In this work, we created a novel, paper-based cantilever sensor array that allows simple and rapid naked-eye VOC detection without the need for power, electronics or readout interface/equipment. This simple VOC detection method was achieved using (i) low-cost paper materials as a substrate and (ii) swellable thin polymers adhered to the paper. Upon exposure to VOCs, the polymer swelling adhered to the paper-based cantilever, inducing mechanical deflection that generated a distinctive composite pattern of the deflection angles for a specific VOC. The angle is directly measured by the naked eye on a 3-D protractor printed on a paper facing the cantilevers. The generated angle patterns are subjected to statistical algorithms (linear discriminant analysis (LDA)) to classify each VOC sample and selectively detect a VOC. We classified four VOC samples with 100% accuracy using LDA.

We report a novel paper-based biobattery which generates power from microorganism-containing liquid derived from renewable and sustainable wastewater which is readily accessible in the local environment. The device fuses the art of origami and the technology of microbial fuel cells (MFCs) and has the potential to shift the paradigm for flexible and stackable paper-based batteries by enabling exceptional electrical characteristics and functionalities. 3D, modular, and retractable battery stack is created from (i) 2D paper sheets through high degrees of folding and (ii) multifunctional layers sandwiched for MFC device configuration. The stack is based on ninja star-shaped origami design formed by eight MFC modular blades, which is retractable from sharp shuriken (closed) to round frisbee (opened). The microorganism-containing wastewater is added into an inlet of the closed battery stack and it is transported into each MFC module through patterned fluidic pathways in the paper layers. During operation, the battery stack is transformed into the round frisbee to connect eight MFC modules in series for improving the power output and simultaneously expose all air-cathodes to the air for their cathodic reactions. The device generates desired values of electrical current and potential for powering an LED for more than 20min.

We developed a stackable and integrable paper-based microbial fuel cell (MFC) for potentially powering on-chip paper-based devices. Four MFCs were prepared on a T-shaped filter paper which was eventually folded three times to connect these MFCs in series. Each MFC was fabricated by sandwiching multifunctional paper layers for two-chambered fuel cell configuration. One drop of bacteria-containing anolyte into the anodic inlet and another drop of potassium ferricyanide for cathodic reaction flowed through patterned fluidic pathways within the paper matrix, both vertically and horizontally, reaching each of the four MFCs and filling the reservoir of each device. Bacterial respiration then transferred electrons to the anode, which traveled across an external load to the cathode where they combined with protons. The MFC stack connected in series generated a high power density (1.2μW/cm(2)), which is two orders of magnitude higher than the previous report on the paper-based MFC stack. This work will represent the fusion of the art of origami and paper-based MFC technology, which could provide a paradigm shift for the architecture and design of paper-based batteries.

In sub-Saharan Africa, nearly a quarter of a million babies are born with sickle cell disease (SCD) each year. An estimated 50-90% of these babies die before age 5 due to lack of early diagnosis and timely treatment. The World Health Organization estimates that more than 70% of SCD related deaths are preventable with simple, cost-effective interventions, such as early screening followed by affordable and widely available treatment regimens. Here, we present the early clinical testing results of HemeChip, which is the first single-use cartridge-based microchip electrophoresis hemoglobin screening platform. HemeChip was developed by Hemex Health, Inc., based on technology licensed from Case Western Reserve University. HemeChip allows affordable, objective, quantitative screening of hemoglobin variants at the point-of-care. HemeChip works with a drop of finger or heel-prick blood and separates hemoglobin variants on a piece of cellulose acetate paper that is housed in an injection molded plastic cartridge with a precisely controlled electric field. HemeChip works with a portable reader to produce easily understandable, objective, and quantitative descriptions of the hemoglobin types and percentages present in a blood sample. The HemeChip reader guides the user step-by-step through the test procedure with animated on-screen instructions to minimize user errors. Hemoglobin identification and quantification is automatically done with a custom software on the reader. HemeChip reader records and analyzes the hemoglobin electrophoresis real-time, and it can wirelessly transmit the test results to a central electronic database, if needed. HemeChip prototype units have been clinically tested and benchmarked against the clinical standard technique in Kano, Nigeria, where the SCD prevalence is the highest in the world. We tested a total of 248 subjects (228 children aged 6 weeks to 5 years in Kano, Nigeria; and 20 adults in Cleveland, Ohio, United States) under institutional review board approval, using both HemeChip and the clinical standard laboratory method, High Performance Liquid Chromatography (HPLC, VARIANT™ II, Bio-Rad Laboratories, Inc., Hercules, California). HemeChip tests were done on eHealth Africa campus in Kano, Nigeria, by trained local healthcare workers using blood samples collected at the nearby Aminu Kano Teaching Hospital. Clinical standard (HPLC) testing was done independently by the International Foundation Against Infectious Disease in Nigeria (IFAIN, Abuja, Nigeria) for the blood samples obtained in Kano or by the University Hospitals Cleveland Medical Center Clinical Laboratories (Cleveland, Ohio) for the blood samples obtained in Cleveland. Test results included the following: homozygous SCD (HbSS), heterozygous sickle hemoglobin C disease (HbSC), heterozygous sickle trait (HbAS), and normal (HbAA). HemeChip identified the subjects with HbSS with 100% accuracy, HbSC with 100% accuracy, HbAS with 98.2% accuracy, and HbAA with 96.4% accuracy in comparison to HPLC (Table 1). Overall accuracy of HemeChip was 97.2% in comparison to HPLC for the subjects tested. HemeChip sensitivity was 100% for all hemoglobin variants tested (Table 2), and specificity was 96.4% for HbSS vs. HbAA, 98.2% for HbSS vs. HbAS, 100% for HbSC vs. HbAS, and 100% for HbAS vs. HbAA. Bland-Altman analysis indicated strong agreement between the quantitative HPLC and HemeChip results for hemoglobin percentages, with a mean bias of -3.2%. HemeChip enables, for the first time, accurate, cost-effective identification and quantification of hemoglobin variants at the point-of-need. HemeChip has been developed based on a versatile, mass-producible microchip electrophoresis platform technology that may address other unmet needs in biology and medicine that require rapid, decentralized hemoglobin or protein analysis, identification, and/or quantification. Disclosures Thota: Hemex Health Inc: Employment. Little:PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; NHLBI: Research Funding; Doris Duke Charitable Foundations: Research Funding.

This work reports a novel microsystem for the sensing and characterization of electrochemically active bacterial biofilm. A three-electrode configuration integrated in the microsystem provided the unprecedented use of electrochemical analysis including electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) for monitoring bacterial electron transfers. Transparency of the device simultaneously visualized different stages of bacterial biofilm development. This technique allowed for both optical and electrical studies of the microbial biofilm and provides valuable information between the cell growth/biofilm development and the extracellular electron transfer processes associated with microbial energy production. In particular, this microsystem demonstrated the potential synergistic cooperation between cyanobacteria and two archetype exoelectrogenic bacterial species, which can be exploited in developing self-sustainable microbial bioelectricity production.

We demonstrate the use of a paper-based sensing platform for rapid and high-throughput characterization of microbial electricity-generating capabilities. For the first time, a 48-well microbial fuel cell (MFC) array was fabricated on paper substrates, providing 48 high-throughput measurements and highly comparable performance characteristics in a reliable manner. Spatially distinct 48 wells of the sensor array were prepared by patterning 48 hydrophilic reservoirs in paper with hydrophobic wax boundaries. The paper-based platform exploited the ability of paper to quickly wick fluid and promote bacterial attachment to the gold anode pads, resulting in an instant current generation upon loading of bacterial inoculum and catholyte. This paper-based 48-well MFC array does not require external pumps/tubings and represents the most rapid and the highest throughput test platform for electrogenic bacterial screening.

We report a microliter-sized (140 µL) microbial fuel cell (MFC)-based biosensor integrated with a three-electrode configuration and an air-bubble trap, in which microorganisms act as the sensor for toxic substances in water. The small-scale MFC biosensor produced favorable conditions for (i) reducing measurement time by increasing the probability of cell attachment and biofilm formation in the micro-sized chamber and (ii) enhancing sensitivity and reliability by providing a stable anodic potential and preventing air bubbles on the sensing surface. Using formaldehyde as a toxic component, the rapid current responses were obtained over a concentration range from 0.001% to 0.1% in a single chambered MFC biosensor with 0.2 V (versus Ag/AgCl reference electrode) applied on the anode.

We report a nine-well MEMS-based parallel analyses platform for testing electricity generation capacity of eight microbial consortia, which provides high throughput characteristics for bacterial electrogenic screening. The presented device features independent fluidic access to each analysis unit allowing for long term analysis ability without contamination from chamber to chamber during operation. The device contains vertically stacked 57μL anode/cathode chambers separated by a proton exchange membrane (PEM) and each device component is thermally assembled without mechanical supporting frames/bolts/nuts. This device will create a compact screening system individually addressable for identification and characterization of electrochemically active microbes.

We report a microfabricated paper-based bacteria-powered battery generating 10 μW/cm 2 . Only four batteries connected in series provided desired values of current and potential to power an LED for more than 30 minutes without power management interface circuits. The battery features (i) a low-cost paper-based proton exchange membrane directly patterned on commercially available parchment paper with laser treatment and (ii) paper reservoirs for holding the anolyte and the catholyte for extended period of time. Since sewage or soiled water in a puddle can become an excellent source for extracting bioelectricity through bacterial metabolism, this paper-based bacteria-powered battery is expected to be a simple, low-cost, and easy-to-use power source for single-use paper-based diagnostic devices in resource-limited settings.

We report a micro-sized microbial solar cell (MSC) that can produce sustainable energy through photosynthetic reactions of cyanobacteria, Synechocystis PCC 6803 in the anode. The MSC has 57-μL anode/cathode chambers defined by laser-machined poly(methyl methacrylate) (PMMA) substrates. We obtained a maximum power density of 7.09 nW/cm 2 which is one hundred seventy times more power than previously reported MEMS MSCs. The importance of the light intensity was demonstrated by the higher values of generated current during daytimes than those through the nights, indicating light-dependent photosynthetic processes. Considering that sunlight offers an unlimited source of energy, development of self-sustainable MSCs that rely on light as an energy source will become an increasingly important area of research in the future. In accordance with the MSC, we developed a photosynthetic cathode-based microbial fuel cell (MFC) showing that the use of cyanobacteria can be useful as well as efficient and sustainable catalysts for the cathode since they act as oxygenators.

We report a microfabricated transparent microbial fuel cell (MFC) visualizing electrogenic bacteria in situ with realtime and simultaneous measurements of bacterial electron transfer. The MFC features a protruded anode chamber which can be directly placed under an optical microscope for observing live bacterial behavior. The MFC had 140 μL-sized anode and 70 μL-sized cathode chambers separated by a proton exchange membrane (PEM). Using this device, a maximum current density of 2.3 μA/cm2 and power density of 5.29 nW/cm2 were achieved. This technique allows for both optical and electrical studies of the electrogenic bacteria and provides valuable information between the cell growth/biofilm formation and the extracellular electron transfer processes associated with MFC operation.

We report a multi-anode paper-based microbial fuel cell (MFC) capable of generating a power density of 28.4 μW/cm2. This MFC features (i) flexible multilayered carbon anodes for bacterial attachment and (ii) paper reservoirs for holding the anolyte and catholyte for an extended period of time. By using the multi-anode MFC, the power and current densities increased by 5x and 3x, respectively, compared to a single anode one. The paper-based MFC is expected to be a simple and easy-to-use power source for single-use diagnostic biosensors because even sewage or soiled water in a puddle can become an excellent source for operating MFCs and harvesting electricity through bacterial metabolism.

We report a paper-based microbial fuel cell (MFC) generating a maximum power of 5.5 μW/cm2. The MFC features (1) a paper-based proton exchange membrane by infiltrating sulfonated sodium polystyrene sulfonate and (2) micro-fabricated paper chambers by patterning hydrophobic barriers of photoresist. Once a sample was added to the device, a current of 74 μA generated without any startup time. This paper-based MFC has the advantages of ease of use, low production cost, and high portability. The voltage produced was increased by 1.9× when two MFC devices were linked in series while operating lifetime was significantly enhanced in parallel.

Due to an increased concern about the global energy crisis and environmental pollution, microbial fuel cells (MFCs) have been a major focus for renewable energy production. To date, however, a surprisingly small number of bacterial strains and their optimal growth conditions have been investigated for use in MFCs, revealing a crucial lack of fundamental knowledge as to which bacteria species or consortia may be best suited for generating power in MFCs. This lack of knowledge is due to the fact that current screening methods are depending on larger scale two-bottle MFCs that require long start-up times, as well as the inability of conventional MFC arrays to generate electricity in a reliable, robust, and reproducible manner. In particular, the influence of light on the bacterial growth conditions and their power generation has not been fully reported because conventional MFC's opaque device/anode configuration leads to inefficient light penetration. This paper presents a miniaturized high-throughput parallel analyses platform not only for the screening/characterization of the electrochemical activities of electrogenic bacteria but also for investigation of the effect of light on bioelectricity generated from eight different microbial consortia in anode or cathode compartment; wild-type Shewanella oneidensis MR-1, Synechocystis sp. PCC 6803, wild-type Pseudomonas aeruginosa PAO1, and isogenic nirS, lasl, bdlA, and rpoS mutants, respectively. The array consists of nine MFC units with (i) transparent thin gold anode on PMMA layers for efficient light penetration and (ii) independent microfluidic accesses allowing for long term analysis ability without contamination from chamber to chamber during operation. Each MFC unit contains vertically stacked 57 μl anode/cathode chambers separated by a proton exchange membrane. S. oneidensis displayed the highest current generation among all the consortia, 4-fold higher than that of wild-type P. aeruginosa PAO1. However, all the other mutants produced significantly low current outputs. Current production by Synechocystis sp. PCC 6803 demonstrated a positive response upon illumination and a subsequent decrease of output in the dark while other MFC units showed negligible light responses.

Application of micro-scale microbial fuel cells (MFCs) to power electronics is limited due to the high internal resistances associated with membranes. Laminar flow MFCs (LFMFCs) provide an advantage over conventional designs because the anode and the cathode are naturally separated due to the laminar flow regime that develops within the reactor, eliminating the need for membranes. However, our ability to fully harness the potential of LFMFC technology lags from a lack of in-depth understanding of anode/cathode analyte mixing and fundamental factors that maximize LFMFC's power-generating capabilities. We, therefore, investigated the anode colonization and respiration of the known exoelectrogenic bacterium, Geobacter sulfurreducens, in a micro-scale LFMFC. Current production was dependent on the location of the anode relative to the influent in continuous-flow operation, with the highest current density of 6.5 μA/cm2 recorded closest to the influent. Lateral diffusion of anode/cathode analytes, in addition to upstream substrate consumption, likely resulted in the observed differences in current production. As current increased, the number of bacterial cells on the anode measured using simultaneous microscopic observation, also increased. Although the current density obtained here was substantially lower than other micro-sized MFCs, these findings show that micro-scale LFMFCs adapted to microscopic observation can provide a unique tool for better understanding real-time anode colonization and overall reactor performance.