Drones As Mobile Microbiological Laboratories

Drones as mobile microbiological laboratories

ESCMIDMario PoljakeLibrary Institute of Microbiology and Immunology Faculty of Medicine, University of Ljubljana, Slovenia © by author. I have no conflicts of interest to declare.

ESCMID eLibrary © by author autonomous, or remotely controlled, multiuse aerial vehicles that are driven by aerodynamic forces and are capable of carrying a payload

definition framed the distinction from other aerial systems like: ballistic vehicles, gliders, balloons, and cruise missiles

ESCMID eLibrary © by author autonomous, or remotely controlled, multiuse aerial vehicles that are driven by aerodynamic forces and are capable of carrying a payload

definition framed the distinction from other aerial systems like: ballistic vehicles, gliders, balloons, and cruise missiles

Drone coined in reference to the early remotely-flown target aircraft used for practice firing of a battleship's guns the term first used with the 1920‘s Fairey Queen target aircrafts

UnmannedESCMID aircraft vehicle/system eLibrary (UAV; UAS) adopted by the United States Federal Aviation Administration in 2005 © by author https://en.wikipedia.org/wiki/Drone

- agricultural drone - delivery drone - micro air UAV - miniature UAV - multi-rotor - passenger drone - quadcopter - unmanned combat aerial vehicle ESCMID eLibrary © by author https://en.wikipedia.org/wiki/Drone

- agricultural drone - delivery drone - micro air UAV - miniature UAV - multi-rotor - passenger drone - quadcopter - unmanned combat aerial vehicle ESCMIDmedical drone eLibrary lab-on-a-drone © by author https://en.wikipedia.org/wiki/Drone

- agricultural drone - delivery drone - micro air UAV - miniature UAV - multi-rotor - passenger drone - quadcopter - unmanned combat aerial vehicle ESCMIDmedical drone eLibraryFixed wing aircrafts lab-on-a-drone UAVs resembling helicopters © by author Fixed wing aircrafts

PROS: can reach high altitudes, travel great distances, relatively high speed CONS: require a preexisting runway or a launching platform

ESCMID eLibrary © by author UAVs resembling helicopters

PROS: have vertical take-off and landing capabilities, easier to navigate in dense, urban environments and even inside buildings CONS: shorter flying range, lower speed, relatively smaller payload capacity

ESCMID eLibrary © by author non-medical use of drones

general medical use of drones

ESCMIDuse of drones eLibrary in CM/ID © by author ESCMID eLibrary © by author Drone a male bee, from an unfertilized egg

Drone a fertile male ant ESCMID eLibrary © by author Drone a male bee, from an unfertilized egg

term ”drone” coined because of the similarity of the loud and cadenced sound of old military unmanned target aircraft to that of a male bee

Drone a fertile male ant ESCMID eLibrary © by author 36 eligible papers

ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author Drone perception

ESCMID eLibrary © by author Drones are crucial component of most prominent national militaries

ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author Drone perception

ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author ESCMID eLibrary © by author delivery of non-medical products by drones despite the early predictions that drones would be used to deliver fast food and other goods, the reality is rather different drone delivery service across Elliðárvogu, an inlet that divides Reykjavik from its eastern suburbs; customers can order goods using online apps and, weather permitting, select a drone delivery; drones do not use cameras or radar to navigate, but GPS; start with fixed routes that gradually become more ambitious small aid packages delivered to communities affected by major disasters: - 2010 - earthquake in Haiti - 2012 - Superstorm Sandy hurricane (US, Canada and the Caribbean) - 2015 - category 5 cyclone (Pam, islands of Vanuatu) - 2015ESCMID - earthquake in Nepal eLibrary drone supply of spare parts to ships anchored offshore in Singapore (March 2019) © by author delivery of non-medical products by drones

delivery of blood, medicines, antivenom, vaccines etc. by drones

ESCMID eLibrary © by author Transfusion 2017;57:582-88

six leukoreduced red blood cell (RBC) and six apheresis platelet (PLT) units units placed in a cooler, attached to the drone, and flown for up to 26.5 minutes with temperature logging after flight, the RBC parent units centrifuged and visually checked for hemolysis; PLTs checked for changes in mean PLT volumes (MPVs), pH, and PLT count no evidence of RBC hemolysis; no significant changes in PLT count, pH, or MPVs; and noESCMIDchanges in the FP24 bubbles eLibrary no adverse impact of drone transport on RBC or PLT units © by author Rwanda is the first country that has sought to integrate drones into its health service with drones used to deliver blood

‘Uber for blood’ service launched in 2016 in the presence of the Rwandan President a fleet of small, battery-powered aircraft-like drones designed and built by a Silicon Valley start-up Zipline International drone service activated by local healthcare workers via text-message ordering service

GPS coordinates of the intended delivery site are used to program the drones and guideESCMID them to their destination, significantly eLibrary reducing delivery times 4,100 units of blood delivered in the first year; delivery time 15-45 minutes; 40% of the blood for postpartum hemorrhaging; 40% for treatment of severe malaria © by author Tanzania launched the world's largest drone delivery network in January 2018 more than 1,000 health facilities across the Tanzania connected dlivery of blood, vaccines and malaria and HIV/AIDS drugs modified Zipline International drones flying at 100 km (62 miles) per hour; drones parachuting blood and medicines with biodegradable parachutes ESCMID eLibrary Tanzania has one of the world's worst maternal mortality rates - 556 deaths per 100,000 deliveries © by author Vaccine 2016;34:4062-7

sensitivity analyses to assess the impact of using drones for routine vaccine distribution vs. traditional multi-tiered land transport system (TMLTS) compared to the TMLTS, drones maintained cost savings in all sensitivity analyses, ranging from $0.05 to $0.21 per dose administered implementing a drone delivery could increase vaccine availability and decrease costs in a wide range of settings and circumstances if the drones are used frequently enough to overcome the capital costs of installing and maintaining theESCMIDsystem eLibrary © by author remote island of Erromango - South Pacific nation of Vanuatu about 20 % of Vanuatu’s 35,000 children under age 5 do not get all their shots many villages reachable only by “banana boats” most villages have no electricity

ESCMID eLibrary © by author Drones are delivering contraceptives to hard-to-reach Ghanaian villages in a program jointly funded by the United Nations and the Bill & Melinda Gates Foundation.

Deliveries to rural Ghana that once took two days now take 30 minutes by drone, and each flight costs only $15.

Program expanding to six other African countries. The goal is to revolutionize women’s health and family planning in Africa. Tanzania, Rwanda, Zambia, EthiopiaESCMIDand Mozambique have expressed eLibraryan interest. © by author IEEE J Transl Eng Health Med 2018;6:4000107 six-rotor UAS used to model situations relevant to organ transportation real-time organ status monitoring using a wireless biosensor combined with an organ global positioning system

14 drone organ missions performed; temp. remained stable and low (2.5°C) biopsies of the kidney revealed no damage resulting from drone travel ESCMID eLibrary © by author delivery of non-medical products by drones

delivery of blood, medicines, antivenom, vaccines etc. by drones

ESCMIDdelivery of samples eLibrary to centralised laboratory by drones © by author PLoS One 2015;10:e0134020

three paired samples obtained from 56 adult volunteers; chemistry, hematology, and coagulation testing

168 samples held stationary vs. 168 samples flown in the UAS (6-38 minutes)

33 of the most common chemistry, hematology, and coagulation tests performed a mean difference of 3.2% for glucose and <1% for other analytes onlyESCMIDbicarbonate did not meet the strictest eLibraryperformance criteria. transportation of laboratory specimens via small UASs does not affect accuracy of routine chemistry, hematology, and coagulation tests results © by author ESCMID eLibrary

Amukele et al. © by author PLoS One 2015;10:e0134020 Am J Clin Pathol 2017;148:427-35

stability of biological samples in prolonged drone flights paired chemistry and hematology samples from 21 adult volunteers half of the samples held stationary, other samples flown for 3 hours (258 km) in a custom active cooling box mounted on the drone

17 analytes had small or no bias glucose and potassium in flown samples showed an 8% and 6.2% bias; the changes consistentESCMIDwith the magnitude and duration eLibraryof the temperature difference between the flown and stationary samples © by author Am J Clin Pathol 2017;148:427-35

ESCMID eLibrary © by author Anal Biochem 2018;545:1-3 proper mixing for homogenous dispersion of silica particles, separator gels, clot activators or anti-coagulants is vital for optimal downstream separation of serum or plasma; controlling the level of agitation applied during mixing is important for minimizing hemolysis of red blood cells which could render the sample unsuitable for testing the ability to transport and mix samples using the simple flip maneuver offered in quadcopters demonstrated ESCMID eLibrary © by author J Clin Microbiol 2016;54:2622-5

6 sets of paired aerobic and anaerobic blood culture bottles inoculated with 10 ml of whole blood and spiked with S. aureus, S. pneumoniae, E. coli, or B. fragilis

2 ml of pooled sputum inoculated with 50 µl of S. aureus or S. pneumoniae from initial concentrations of 1 McFarland, 1/10 McFarland, and 1/100 McFarland standards blood and sputum specimens flown in a drone for 30±2 min ESCMIDtimes to recovery, colony counts, morphologies, eLibrary MALDI-TOF MS-based identifications of the flown and stationary samples similar for all microbes © by authorstudied South Afr Med J 2017;97:1215-8 e-Juba (electronic pigeon) project to address pre-analytical phase of the laboratory logistic loop in remote areas of South Africa centralised laboratories serve approximately 20 clinics each, which are located approximately 10 - 30 km distant mini drone designed to transport a payload of up to 500 g over a distance of up to 40 km via GPS the cargo bay for medical samples in the fuselage directly below the wing basicESCMIDGPS pilot (excluding antenna), barometric eLibrarysensors and flight stability systems weighs in at only 28 g © by author DHL used a Wingcopter to fly medical supplies from Mwanza, on the shores of Lake Victoria, some 60km to a clinic on Ukerewe Island; blood and other samples from the clinic‘s patients were then flown back to Mwanza for laboratory analysis; the drone transport 40 minutes vs. six hours by road and ferry

MSF evaluated a drone-based system for delivering laboratory samples to hospitals for tuberculosis testing in partnership with the logistics company Matternet in 2014; a battery-powered, prototype multirotor quadcopter that had been tested in Haiti in 2012 was modified for collecting and transporting packaged sputum samples and operated by mobile phone in Malawi, MSF drones are being tested by Unicef and Matternet for the delivery of pediatric blood samples for HIV testing; blood samples from rural HIV clinics are currentlyESCMIDtransported by motorbike, whicheLibraryrequires a large batch of samples to make the journey cost-effective © by author ESCMID eLibrary © by author delivery of general medical equipment by drones

ESCMID eLibrary © by author J Spec Oper Med 2018;18:34-35.

rotary-wing drone simulated delivery of a customizable 4.5 kg load of medical equipment, including tourniquets, dressings, analgesics, and blood products to a remote environment where vehicle or foot traffic is impossible or impractical medical supplies delivered successfully within 1 mile of the target; time from launch to delivery was 20.7 min; resupply by foot would take 5.1 hours the drone successfully returned to the starting point every flight

ESCMID eLibrary © by author Circulation 2017;135:2454-65 Boutilier J. J., Brooks S. C., Byers A. J. A., Buick E. J., Zhan C., Schoellig A. P., Cheskes S., Morrison L. J., Chan T. C. Y.

public access defibrillation programs can improve survival after out-of-hospital cardiac arrest, but automated external defibrillators (AEDs) are rarely available for bystander use at the scene mathematical model; 53,702 out-of-hospital cardiac arrests that occurred in the 8 regions of the Toronto Regional RescuNET between 2006-2014 the region-specific analysis determined that 81 bases and 100 drones would be required to deliver an AED ahead of median 911 response times by 3 minutes in the most urban region, the 90th percentile of the AED arrival time was reducedESCMIDby 6.5 min relative to historical 911eLibraryresponse times in the region in the most rural region, the 90th percentile was reduced by 10.5 minutes © by author Circulation 2017;135:2454-65 Boutilier J. J., Brooks S. C., Byers A. J. A., Buick E. J., Zhan C., Schoellig A. P., Cheskes S., Morrison L. J., Chan T. C. Y.

ESCMID eLibrary © by author Circulation 2017;135:2454-65 Boutilier J. J., Brooks S. C., Byers A. J. A., Buick E. J., Zhan C., Schoellig A. P., Cheskes S., Morrison L. J., Chan T. C. Y.

ESCMID eLibrary © by author Characteristics of drone flights vs. EMS in Stockholm, Sweden, October 2016

ESCMID eLibrary © by authorClaesson et al. JAMA 2017;317:2332-34 delivery of general medical equipment by drones

delivery of standard POC microbiological instruments and reagents by drones

ESCMID eLibrary © by author Rent-a-POC concept

H H H POC POC POC

ESCMIDPOC storage, maintenance, eLibrary calibration and QC clin micro lab © by author POC = point-of-care Selected compact “sample in-results out“ molecular diagnostic devices

Cepheid GeneXpert GenMark Dx eSensor Roche cobas Liat System Veredus VereChip Alere iSystem Great Basin Portrait Luminex ARIES Focus Dx Simplexa/3M Cycler Atlas Genetics QuidelSavanna & Solana Enigma Diagnostics Meridian Illumigene Micronics BD Max System Cirrus Dx T-COR 8 ELITe InGenius Systems BioFire FilmArray Biomeme Nanosphere Verigene SP Fluoresentric, Inc. QuantuMDxESCMIDGeneWEAVE eLibrary VivoDx Janssen Diagnostics Rheonix Encompass Optimum © by author Circulation 2017;135:2454-65 Boutilier J. J., Brooks S. C., Byers A. J. A., Buick E. J., Zhan C., Schoellig A. P., Cheskes S., Morrison L. J., Chan T. C. Y.

delivery of standard POC microbiological instruments and reagents by drones

portable biochemical analysis using consumer-class quadcopter drones isothermally perform PCR (convective thermocycling) with a single heater; system operated using standard 5 V USB sources that power mobile devices (via battery, solar, or hand crank action) time-resolved fluorescence detection and quantification achieved using a smartphoneESCMIDcamera and integrated image analysiseLibraryapp standard sample preparation enabled by leveraging the drone’s motors as centrifuges via©3D printed bysnap- onauthorattachments successful in-flight PCR amplification using convective thermocycling Lab-on-a-drone of two different DNA targets (16 min in-flight reaction time)

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PCR product yields are insensitive to the reactor’s orientation with respect to the vertical direction up to tilt angles of at least 60°

ESCMID eLibrary © by author Anal Chem 2016; 88: 4651−4660 Lab-on-a-drone time-resolved fluorescence detection and quantification using a smartphone camera and integrated image analysis app

Drone-based centrifugation benchtop centrifugation processes are challenging to miniaturize by removing the quadcopter propellers and replacing them with 3D printed centrifuge rotors designed to fit the motor shaft threading

Drone-based sample preparation standard centrifuge-based workflows allowed in lab-on-a-drone 3D printed attachments transform the quadcopter into a centrifuge capable of rotationESCMID speeds up to 10,000 rpm eLibrary standard column-based extraction of Dengue viral RNA from human serum yielded results on par with those obtained from samples processed using a benchtop centrifuge © by author Drones

infectious diseases surveillance ESCMIDand epidemiology eLibrary © by author equipped with sensor and artificial intelligence capacities, drones are able to read the environment, providing georeferenced data on temperature, water, salinity, and vegetation

Monkeybar, launched in 2013, is a multidisciplinary collaboration using drones as active data-collection devices to map the ecological conditions and changes that are driving the spread of zoonotic malaria into human populations fixed-wing eBee drones (senseFly, Switzerland) deployed to better understand the epidemiology of the simian malaria by mapping interrelationships between people, the macaques that harbour the vector, and wildlife reservoirs

ESCMID eLibrary multicopter drones equipped with thermal cameras employed to track the movement of macaques via their ‘heat signature’ © by authorPeckham and Sinha, Glob Public Health 2018:1-16 Parasit Vectors 2017;10:29

low-cost (<$1,000) drone (DJI Phantom) for mapping water bodies in seven sites across Zanzibar including natural water bodies, irrigated and non-irrigated rice paddies, periurban and urban locations low-cost and flexible solution to mapping water bodies for operational dissemination of larval source management initiatives in mosquito vector-borne disease elimination campaignsESCMID eLibrary © by author PLoS Negl Trop Dis 2019;13:e0007105

use of drones for identifying Nyssorhynchus darlingi breeding sites with high- resolution imagery (~0.02m/pixel) and their multispectral profile in Amazonia high resolution multispectral imagery can discriminate a profile of water bodies where Ny. darlingi is most likely to breed (overall accuracy 86.73% - 96.98%)

ESCMID eLibrary © by author PLoS One 2014;9:e115608 spatial pattern of hosts’ distribution and abundance is crucial for modelling the determinants of disease transmission and persistence on a fine spatial scale. spatial epidemiology of tuberculosis in the ungulate community of Doñana National Park (South-western Spain) by modelling species host (red deer, fallow deer and cattle) abundance at fine spatial scale

virome diversity in aquatic mammals unknown due to difficulties in sampling virome of the exhaled breath (or blow) of the Eastern Australian humpback whale characterised using samples collected from 9 whales via a purpose-built drone approximately 3 km off the coast of Sydney, Australia during the 2017 winter annual northward migration from Antarctica to northern Australia

the potential drone applications in medicine are extensive and may be transferrable worldwide and revolutionise some fields of medicine the potential for drone technology in infectious diseases, clinical microbiology and epidemiology is vast, and hopefully the technology will be able to fill niches where our performance needs improvement widespread use of drones face challenges such as national legislations, climate zones and topography, medicolegal and licensure issues, finance and reimbursement, as well as community attitudes and acceptance in different culturesESCMID and nations eLibrary © by author Lancet Haematol 2017;4:e56