Journal ofPrecisionJournal Medicine | Volume 7 | Issue 2| June 2021 thejournalofprecisionmedicine.com by the device. to the networks of biomolecular measure signals (the Internet, computers, and our phones) cell is to provide ameans to connectnetworks digital transistor’sin the substrate. Cardea Bio’s mission on transistor’s the signal to surface an electrical transistor that bridge binding biology events receptor biomolecules on gate the of agraphene TheCardea’s to key approach is to stabilize eventssurface generated to asignal inasubstrate. class of that devices transduce biological binding Cardea Bio has up taken challenge this with anew accessible for monitoring innear-real time. technologies to make molecular control signals directly toto biology various link read-out An interviewwith @journprecmed MANY EFFORTS IN We contacted Michael Heltzen and Brett Bioelectronics of Precision Medicine – The nextgeneration the past the have made been Michael HeltzenandBrett Goldsmith (lateral flow, surface plasmon resonance (SPR), advantages over traditional measurement platforms A. to competitive systems? differentiate itsperformancerelative In this regard, howdoesCardea Bio of e.g.,sensitivity, selectivity, speed? related measurement platformsinterms brings tothemarketcompared to Q1. and clinic. inthe advance precision development medicine indrug directed to how platform this to used could be on and technology the applications of device the Goldsmith of Cardea Bio to ask afew questions The CardeanThe distinct several Infrastructure has What are thebenefitsthatCardea Bio Journal ofPrecisionJournal Medicine | approximation at Where optics-based best. produce adetectable providing signal, an indirect rely bound tags to on target the secondary to cannot amino directly detect acids; rather, they detection. Additionally, optics-based technologies target to minimum the molecule meet threshold for (e.g. NGS) require mass-amplification the the of example, technologies that measure nucleotides optically. them to observe needed As aresult, for are oftenthanthe wavelengths smaller of light measurement; aim to they detect molecules the contain an inherent limitation it when comes to prep for optics) nearly old. ahalf-century outdated and methods (e.g. sample technology sequencing (NGS), etc.), many of contain which Bio-Layer Interferometry (BLI), next-generation Optics-based technologies (SPR,Optics-based BLI) Volume 7 | Issue 2| June 2021 61 The Journal of Precision Medicine 62 The Journal of Precision Medicine overall transistorproperties. Figure 2:Adiagramdescribing theactionofCardeanbiology gatedtransistorafterexposureto theanalyte.Bindingtocapture chemistrycausesa changeinthe wavelengths of light –allowing us to directly thatcan molecules detect are than visible smaller near real inlive time data streams. system Our quantitate inquestion biological the signal in technologies. Cardea is able to directly read and that can influence results, withas optical studied,being or cause non-specific interference thattags can interfere with biomolecules the Cardea’s direct not detection does rely on any limitations of optics-based technologies. protocols, and extensive training. require cumbersome equipment, complex experiment. Finally, many traditional technologies monitoringtime capability over course the of the interaction, electronic detection provide anear-real technologies provide asnapshot of abiological The graphene isconstructedtobepartofaliquidgatedtransistor. Atthestart,there isnothingboundtothecapture chemistry. Figure 1: AdiagramdescribingtheactionofCardean biologygatedtransistor. Acapture chemistrysuchasanantibodyisconnectedtothegraphenesurface. Journal ofPrecisionJournal Medicine | The CardeanThe Infrastructure overcomes Volume 7 | Issue 2| June 2021 Figures 1and signals 2).These are intofed machine read as be arobustthen (as diagrammed signal in properties of graphene the electrical the that can ofsurface our transistor, binding the event changes binds to capture the mechanism immobilized to the bindmolecules near surface. the When our target environment such caused two when as those It sensitive very to is changes also inits charge directly in salt-solutions, such as biological fluids. goldunlike and silicon it because can operate of our transistor. Graphene biocompatible, is highly detection by usingelectrical graphene at core the and small molecules. genes, single nucleotide polymorphisms (SNPs), activity without amplification, including whole detect biomarkers in minutes, as well as binding We potentiate further capabilities the of direct ordering to BLI. platform that has demonstrated comparable rank validation. This adds another fast, cost-effective, with to respect “hitscreenings, especially to lead” and primary secondary via discovery to dodrug A. In drugdevelopment? medicine applications: Cardea Bio envisionforprecision Q2. unparalleled sensitivity, selectivity, and speed. of Cardea Infrastructure is already capable of understanding of biology. the current The generation sample-to-answer as times well as letting us gain an learning algorithms that improve and accuracy Cardean transistors are by used our partners What portfolio of assays does What portfolioofassaysdoes 1 thejournalofprecisionmedicine.com @journprecmed Journal ofPrecisionJournal Medicine | Volume 7 | Issue 2| June 2021 Journal ofPrecisionJournal Medicine | Volume 7 | Issue 2| June 2021 thejournalofprecisionmedicine.com multiple sensorsinside thecircularwell. Figure 3:AstandardCardean chipcontaining for our future to partners utilize our for technology A. office foratherapy? an assessmentofapatientindoctor’s companion diagnosticsapplicationfor, say, Q3. “Powered by Cardea” partners. bottlenecks identified and understoodwell by our demand to solve anumber of costly problems and no or low regulatory hurdles and astrong market development.path This offers a combinationof to deploying product our via technology fastestthe moving markets inregard we see applications like www.CRISPRqc.com are A. R&Dlabs instruments and “quality control” In theR&Dlab? diagnostic, or monitoring scenarios. way to understand patient inprognostic, health have ability the to provide atransformational after vaccination or immunotherapies, partners our diagnostics to monitoring of immune responses assays for screening to infectious newborn disease ways not available previously. From enzymatic of rapid point of care (POC)/point of testing in A. In theclinic? trials. clinical to provide acutting to‑edge technology support of presents these an opportunity for our partners inclusion/exclusion criteria, and many more; each biomarker assays, to genetic screening for From real-time pharmaco-kinetics (PK), to range of applications during trials. clinical A. In clinicaltrials? @journprecmed Companion diagnostics represent agreat place We our as enabling technology see field inthe Cardea’s platform for used could be awide Does Cardea Bio plan to develop Does Cardea Bio plantodevelop Cardean transistors. a product compatible with workings the of our pulling “Lego” best the blocks together to create what is already established marketplace, inthe assay requirements. At Cardea, we leverage processing individual to meet specifically designed thatcartridges would enable onboard sample into range awide of off-the shelf microfluidic in integration of our biology-gated transistors processwill and read sample. the We are experts drop of sample the on machine the acartridge; handling. For or blood urine, simply place a require rapid results with to minimal no sample indication.use For example, tests most POC would dependent be on assay the and end- biological fluidsample. The sample preparation rely on optics, platform the can inany function A. of in‑laboratoryapplications? preparation are neededforin-office urine? What typesofsample platform support–blood,sputum, what sampletypesdoestheCardea Q4. InfollowuptoQ2andQ3, to improve patient outcome. condition and actionable can those use insights complete and near instant picture of apatient’s disposable chip. Thus, a physician get a will more to build products that combine it on all asingle third to enzymatic assay, able be our will partners sequencing, another for an immunoassay, and a multi-omics chip. Instead of sending asample to to combine individual tests several into one beautyThe of our system is its imminent ability cellular components like exosomes to metastasize. orsignals, of evidence cancer cells hijacking mutations or abnormalities, active cellular destress most effectivethe context in of identified genetic but to assess also treatment which would be an opportunity not only cancer to diagnose early, (forChip sets gene or SNP mutations), presents (for intercellular communication) or CRISPR- techniques, such as with our InterCell-Chip is agreat example of The this. use of liquid biopsy treatment. The opportunitywith cancer treatments rapid stratification patientsof the to appropriate For more informationaboutCardea BioInc. impact viainnovativeapplications. partners withTech+Bio solutionsthatwillenable to Life,”empowerits“Powered byCardea” Cardea isonalong-termmission,“Linkingup ‘Linking uptoLife’ visit www.cardeabio.com Being an all-electric system that not an does all-electric Being

Journal ofPrecisionJournal Medicine | strategy to use will be dependent be onstrategy to will the use A. CMS andotheragenciesworldwide? plans toapplyforreimbursement withthe Q7. InfollowtoQ6,doesCardea Biohave products quickly to consumers. partnershipwin-win that delivers safe and effective most effect roadmap foreach product to createa market. We work with our Partners to the identify our Partner’s commercial goals and intended use individualized regulatory strategy by determined with our Innovation Partners would require an and consumers. their product Each we design safe and effective products for partners our markets, and we arebeliever in afirm providing path for us to support our inregulated partners certifications. be acritical thiswill believe We we intend ISO9001and to seek ISO13485 integratedbe into variety of awide products, A. these lines? have aroadmap andstrategyalong the EU,andelsewhere? DoesCardea Bio regulatory compliance intheUS,UK, Q6. Whatare Cardea Bio’s plansfor by Cardea” product. topartners market and distribute “Powered their and application. the Cardea relies then on its a CLIA-waived LDT depending on market the appropriate route, acleared whether IVDkit or regulatory and commercial teams an to devise inregulatedpartners markets, we help their markets, regulated both and unregulated. For our of opportunities for Cardea breadth the runs of disruptive products markets. intheir This universe Partners to to technology create utilize this A. developed testroute? diagnostic kit,orwillitgothelaboratory- to marketanFDA-approved invitro its products? DoesCardea Biointend respect toFDAapproval and marketing Q5. or Cardean Transistors™. Graphene-based Biology-gated Transistors, Chipsets manufactured withproprietary (hardware, software, wetware) andCardean technology consists ofaTech+Bio Infrastructure molecular signalsrunningbiology. Itsmulti-omics Cardea islinking computerstotheLIVE Linking computers The decision which of reimbursement As amanufacturer of biosensors that will Cardea works by enabling our Innovation What are Cardea’s planswith Volume 7 | Issue 2| June 2021 63 The Journal of Precision Medicine 64 The Journal of Precision Medicine in years (aphotograph of astandard chip is shown for under $50,a100+fold reduction incost in8 to produce achip; now we are producing chips in2013,itstarted cost tens of thousand dollars have continued to beat Moore’s law. When we first Sincewith founding scale. the of our company, we massively semiconductor scaled fabs, price falls semi-conductor manufactured technology in screening instruments, and as our chips use way the all up to large multi-well high-throughput anything from asingle sample handheld devices A. clinical laboratories? cost competitionwithdatageneratedin Cardea positionitsdeviceinlightofthe plates toreduce per-sample costs.Howwill samples from manypatientsinamulti-well advantage ofmeasuringstandards and Q8. next-generation precision diagnostics. disruptive technologies to our to partners create companies like Cardea inproviding highly reimbursement pathway.greatly will This assist Medicarenew Coverage of Innovative Technology authorization and lasting up to 4years of as part the to Breakthrough that receive Devices FDA CMS decision to grant Medicare coverage FDA. Additionally, we are encouraged by the unique the meet demands of CMSand both performance studies and to trial clinical concurrently to effectively set up analytical enable communication organizations with both utilizing FDA’s programs review parallel that CMS reimbursement, we recommend highly If our Innovation Partner desires to apply for partner’s commercial and regulatory strategies. Journal ofPrecisionJournal Medicine | linked directly intoelectronics andcomputers. that togetherallowforlivesignalsinbiologytobe and thebiology-gatedTransistors from Cardea, combining thenaturalsearch powerofCRISPR a handhelddevice.TheCRISPR-chipworksby time measurement, anditcanevenbebuiltas a specificgene CRISPR-chip canreport ifagenomicssamplehas Engineering (Nature BME)publications. as demonstratedintwoNature Biomedical DNA workflowstepsthat require aDNAlab, the needforamplificationorothernormal capability tosearch through genomeswithout The Cardea chipsetcalledCRISPR-Chiphasthe need ofaDNAlab DNA detectionwithoutthe CRISPR-Chip –Electronic Figure 3).Future generations and chip new Our biology-gatedOur transistors chips sit in will Clinical laboratory tests take Clinical laboratoryteststake 2 ormutation Volume 7 | 3 in it as a near real initasanearreal Issue 2| 2,3 The The June 2021 Doctors need toolsDoctors need that provide modular, to deliver on promise the of precision medicine. by centurytechniques. 20th these individuals’ unique that biology cannot provided be Precision medicine requires understanding adeep of to solve complex the problems age. of modern the techniques that were invented 30-50years ago to try A. Q10. Finalthoughts? as either an additional feature step. or as aQC adding Cardea to the technology existing devices arepartners already discussing possibility the of actionable insights. For example, we and our algorithms to draw conclusions meaningful and it can integrate easily with other and data types multi-omicOur data is electronic and so digital by asingle data point from asingle molecule. of studied being biology the than provided can be in near real-time provides amuch clearer picture system. This multi-omicdata stream is available DNA, proteins, pH,and more on all same the that can and detect measure pathogens, cytokines, – we provide amultiplex and multi-omic system our allows technology for understanding new this understand it at asystems level. Thecapability of to integrate of all life’s able to signals be to A. medicine analyses? (‘omics, imaging,etc)usedinprecision integrating itsdatawithothertypes Q9. optimized for different markets. upgraded features withcan new be or tests that are multiplexing testing or measurement solution that parameter but instead having modular and atruly assayeach new or amachine for each“-omic” means not needing to buy machine anew for for assay eachnew or class of biomolecule. This and hardware the not reinvented does to need be breadth of biomarkers. The system is modular, continually mutating pathogens and awider to update workflows to, for example, detect reprogrammable to keep up with need the users to operate or analyze data. the handlers and robots that donot require expert automatedfully high-throughput liquid lab-based microfluidic cartridges, to size hugeand industry where assays inside performed can disposable be that can range from ahandheld reader POC are inexpensive and low-powered electronics cost below adollar. Ontop of our this, readers designs hold potential the to drive consumable What we is arevolutionary need technology Additionally, our system is entirely In 21st the century we are continuing to use Thevision of our company be is able to What are Cardea Bio’s plansfor providing everybody with Precisionproviding Medicine. everybody communityglobal to deliver on promise the of people’s and health, that someday may enable the of providing amore complete understanding of tech+bioa modern that infrastructure is capable forward to empower our with partners chipsets and and multiplexing capabilities, we are pushing sensitivity, specificity, modularity, speed, scalability, many differentsolutions. With unparalleled as foundation the for our many differentpartners’ with world the around us. We our technology see understand our own and biology how it interacts forneed asignificantlybetter and fastersolution to technologies.science It global highlighted the limitations of current diagnostic testing and life enable potential the of precision medicine. and monitoring tools available at to bedside the Program to make next the generation of diagnostics companies through our Innovation Partnership with otherpartnering diagnostic and life science to manufactureneeded tools. We these are actively providesOur technology infrastructure the to power bedside the better informed decisions. multiplex, and multi-omic streams of data at 3. 2. 1. References papers in ScienceandNature Nanotechnology. researcher onlandmarkFieldEffect Biosensing Intelligence CommunityFellowandisthelead heading uptheleadershipteamatCardea BioInc. EXO Incubator, NanosensandBlueSEQ before He hasheldleadershippositionsatCLCbio,BGI, The pandemic painfully magnified the pandemic Thethe painfully magnified Nat BiomedEng.2021. Cas9 immobilizedonagraphene field-effect transistor. single-point mutationsin unamplifiedgenomicDNAvia Balderston, S.,Taulbee, J.J.,Celaya,E.etal. Discriminationof 3, 427–437. a graphenefield-effect transistor. NatBiomedEng.2019; unamplified targetgenesviaCRISPR–Cas9immobilized on Hajian, R.,Balderston,S.,Tran, T. etal.Detectionof 2020; 13(12):419. Inhibitors KillGlioblastomaStemCells.Pharmaceuticals. Sandoval JA,Tomilov A,DattaS,etal.Novel mTORC1 graphene labs. Brett was an graphene labs.Brett wasan from oneoftheworld’s leading the UniversityofPennsylvania, lives. Brett wasapost-docat products thatchangepeople’s nanoelectronics technologyto Brett’s passionisapplying Brett Goldsmith and Intercellular communication. Next-Gen Sequencing,Genomics, development inBioinformatics, background intechbusiness Cardea. Michaelhasanextensive Biology leadershipandstrategyat Michael spearheadsDigital Michael Heltzen thejournalofprecisionmedicine.com

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