FirePlex? and miRNA assay publications

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?Researchers around the globe are forging new biomedical frontiers with FirePlex miRNA and immunoassays.  From biotechnology to clinical care, FirePlex profiling technology provides the analytical power to ask new questions, drive new avenues of research and provide the answers that drive medicine forward.

The superior performance of FirePlex assays and their ability to push the bounds of biomedical research is reflected in the publication record and representation in the highest impact journals.

Find out how the FirePlex^? particle technology works to allow multiplexed analysis from 5 to 400 miRNAs simultaneously in a single sample, or up to 70 protein analytes.

Contents

FirePlex immunoassay publications
FirePlex miRNA publications
Meeting abstracts and reports
FirePlex particle technology publications
News and reviews
Publications by the FirePlex team

1. FirePlex^? immunoassay publications

FirePlex immunoassays are new to the scene and are starting to emerge in high-impact publications as a powerful tool for analyte profiling. FirePlex multiplexing data is helping researchers reveal immune defense mechanisms against infectious diseases, as well as pathology behind immunological dysfunction.

• Find out more about FirePlex Immunoassays

Laval K, Vernejoul JB, Van Cleemput J, Koyuncu OO, Enquist LW.(2018) Virulent PRV infection induces a specific and lethal systemic inflammatory response in mice. JVI.01614-18.

• FirePlex immunoassays reveal that mice with pseudorabies virus (PRV) have circulating pro-inflammatory cytokines (IL-6 and G-CSF), chemokines (Gro-1 and MCP-1) and C-reactive protein, which cause systemic neuroinflammatory symptoms and ultimately death. These findings indicate novel pathogenic mechanisms of PRV and closely related viruses such as human herpes and chickenpox viruses, providing new diagnostic and treatment opportunities.

LeFrancais E et al. (2018) Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury. JCI Insight. 3(3).

• The authors use FirePlex immunoassays to quantify pro-inflammatory cytokines (TNF-α, IL-1β, IL-10, IL-12, IFN-γ, MCP-1, and IL-6) directly from bronchoalveolar (BAL) fluid of mice (Mouse Inflammation Multiplex Immunoassay Kit), demonstrating how lung infections induce innate immune responses that damage host tissues, thereby increase susceptibility to pneumonia. Additional confirmation in human patients suggests new preventative strategies against pneumonia.

Yánez DC et al. (2018) IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation. Eur J Immunol.

• The authors examine Th1 and Th2 cytokines in mice with FirePlex immunoassays to show that interferon-inducible transmembrane (Ifitm/Fragilis) genes skew CD4+ T cell differentiation towards Th2 polarization, and thereby cause immunopathology in allergic airway diseases.

2. FirePlex^? miRNA publications

2.1 Clinical-focused studies

Researchers are using FirePlex miRNA assays to define and utilize biomarkers across the medical landscape, from disease diagnosis to treatment selection and patient monitoring. By enabling these precision medicine approaches to clinical care, FirePlex is progressing medical capabilities against the most challenging diseases, from cancer to autoimmune disease and everything in between.

2.1.1 Cancer/Oncology

Elias KM et al. (2017) Diagnostic potential for a serum miRNA neural network for detection of ovarian cancer. Elife. 6.

• Ovarian cancer is a particularly deadly cancer, with 5-year survival rates averaging only 25-30%, due to lack of early detection methods. Most women are diagnosed only after the onset of symptoms, at which point the disease has already metastasized.  Current biomarkers and early screening tests lack sensitivity, have high false positive rates and fail to detect cancers at early enough stages for successful treatment.
• To identify early biomarkers of ovarian cancer, the authors sequenced miRNAs from 179 human serum samples and utilized machine learning to identify signatures of early-stage disease. The resulting predictive algorithm was tested against 454 patients with various diagnoses and demonstrated 100% specificity for ovarian cancer. The model was further validated with FirePlex miRNA analysis of 51 clinical serum samples, demonstrating positive and negative predictive values of 91.3% and 78.6% respectively. Relevant miRNAs were expressed in pre-metastatic lesions from patients, confirming their origin and biological relevance.
• This study demonstrates the importance of FirePlex miRNA analysis as a complementary tool for biomarker identification and validation in a clinical context. The authors ultimately identify a pattern of seven circulating miRNAs that predict stage I and II ovarian cancers prior to metastasis. The highly specific signature which can discriminate between metastatic and non-metastatic forms of disease may be developed into non-invasive early screening tests to vastly improve ovarian cancer survival rates. In addition, these miRNA may reveal important biological process that contribute to early cancer growth, providing targets for more effective treatment.

Leng Q, Wang Y, Jiang F. (2018) A Direct Plasma miRNA Assay for Early Detection and Histological Classification of Lung Cancer. Transl Oncol. 2018 Aug;11(4):883-889.

• Early detection and subclassification of lung cancers is essential to improve patient prognoses and survival rates with personalized and earlier interventions. For example, if detected during Stage IA, the 5-year survival rate is 85%, compared to only 10% if detected in Stage IV. Meanwhile different subtypes of disease have differential response rates, overall survival, and toxicity profiles from certain therapies.
• FirePlex miRNA assays were utilized to quantify 11 tumor-associated miRNAs directly from 20 μL of plasma of 56 lung cancer patients and 28 cancer-free control patients. Two miRNA were identified as diagnostic markers of lung cancer, with the ability to distinguish between squamous cell carcinomas and lung adenocarcinomas. In other studies, these biomarkers are reported to contribute to disease development and progression and regulate tumor cell susceptibility to immune attack and radiation treatments.
• The authors show that FirePlex miRNA assays offer a preferred method to quickly and easily profile low-abundance miRNAs directly from plasma, whereas other miRNA profiling technologies require prohibitively large plasma volumes and complex downstream processing, which can skew results and lead to poor diagnostic performance of chosen biomarkers. The study derives a predictive miRNA signature that is easily assessed by simple blood draw, representing a promising non-invasive diagnostic tool for earlier lung cancer screening and precise subtype classification to personalize treatments and improving patient outcomes.

Our head-to-head comparison of the FirePlex Assay and qRT-PCR demonstrates that the FirePlex can eliminate intra-assay variables and improve reliability of miRNA quantification by directly targeting crude plasma and minimizing the complicated workflow.

Adams BD et al. (2015). miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple Negative Breast Cancer.  Cancer Res. 2321:2015.

Adams BD et al. (2018) Exercise and weight loss interventions and miRNA expression in women with breast cancer. Breast Cancer Res Treat.  170(1):55-67.

Finotti A et al. (2018)  Liquid biopsy and PCR-free ultrasensitive detection systems in oncology (Review) Int J Oncol. 53(4):1395-1434.

Giles ME et al. (2018) Personalized RNA-medicine for pancreatic cancer. Clin Cancer Res.  24(7):1734-1747.

Joerger M et al. (2014) Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05). Lung Cancer 85(2): 306-313

Le MT et al. (2014) miR-200–containing extracellular vesicles promote breast cancer cell metastasis. J Clin Invest. 124(12):5109-28.

Li B. (2017) Clinical Analysis of OncomiR - Therapeutic Targeting of Tumorigenesis and Tumor Disease. IJGPMB 2(2), 28-35.

Pregibon D and Plieskatt J. (2016) Detecting Circulating miRNA Biomarkers: Challenging Biobank Samples are Evaluated in Parasite-Induced Cholangiocarcinoma Study. Genetic Engineering and Biotechnology News 36(21)

Santos, MT et al. (2018) Molecular classification of thyroid nodules with indeterminate cytology: development and validation of a highly sensitive and specific new miRNA-based classifier test using fine-needle aspiration smear slides. Thyroid 0(JA)

Telonis, AG, Rigoutsos, I. (2018) Race Disparities in the Contribution of miRNA Isoforms and tRNA-Derived Fragments to Triple-Negative Breast Cancer. Cancer Res. 78 (5):1140-1154.

Van Roosbroeck K, et al. (2018) miRNAs involvement in the pathogenesis of Richter’s syndrome. Haematologica. Haematologica 103 (11)

Zhang Q et al. (2014). Molecular analyses of 6 different types of uterine smooth muscle tumors: Emphasis in atypical leiomyoma. Cancer 15;120(20):3165-77.

2.1.2 Diabetes/Metabolic Disease

Flowers E et al. (2015). Circulating microRNA-320a and microRNA-486 predict thiazolidinedione response: Moving towards precision health for diabetes prevention. Metabolism S20026-0495(15)00156-0.

• Current limitations in identifying individuals with insulin resistance prevent early interventions to thwart disease progression, limiting preventive measures against downstream diseases including type 2 diabetes, cardiovascular disease, cancers, polycystic ovarian syndrome, and non-alcoholic fatty liver. Meanwhile, thiazolidinediones (TZDs) can improve insulin sensitivity and stave off type 2 diabetes, but also has adverse side effects and variable response rates which limit its clinical use. Tools to select patients likely to respond to TZDs, or to exclude patients at high risk of adverse events, would significantly improve TZD’s clinical utility against the growing epidemic of metabolic syndrome.
• FirePlex miRNA analysis of 25 different miRNAs previously implicated in type 2 diabetes, insulin and glucose metabolism revealed five differentially expressed miRNAs between in the blood of insulin-resistant vs. sensitive patients.  Of insulin resistant patients given TZDs, 6 miRNAs were differentially expressed between responders vs. non-responders.
• These miRNA signatures provide critical tools for early screening and detection of metabolic disease and downstream comorbidities, identifying patients prior to developing serious illness for more effective preventive interventions. In addition, these signatures will improve the success of TMZ intervention by stratifying patient populations into responders and non-responders, while excluding those at risk of drug complications.
• These biomarkers may also point to specific downstream diseases, reflecting disease heterogeneity and unique pathological mechanisms. As such, they might have clinical utility in identifying patients at risk of cardiovascular disease versus fatty liver, etc., thereby guiding individualized disease prevention and monitoring at early Stages. These early disease-specific biomarkers may also reveal molecular pathways of disease progression, identifying novel therapeutic targets for preventative treatments.

Listen to the webinar where Dr Elena Flowers of UCSF discusses how circulating microRNAs are emerging as useful biomarkers for evaluating changing environmental and behavioral risk factors associated with Type 2 Diabetes.

Flowers E, Aouizerat B, Gadgil M, Kanava A. (2015) Circulating MicroRNAs Associated with Glycemic Impairment and Progression in Asian Indians. Biomark Res. 3(22)

Flowers E, et al. (2017) Preliminary evidence supports circulating microRNAs as prognostic biomarkers for type 2 diabetes. Obes Sci Pract. 3(4):446-452.

Kamalden TA et al. (2017) Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress. Antioxidants & Redox Signaling 27(13)

Joshi A, Goetzl L, Pinney S. (2018) Effect of Gestational Diabetes and Maternal Obesity on Fetal Programming—Are miRNAs Key Epigenetic Modifiers or Biomarkers of an Altered Intrauterine Milieu? Diabetes 67(Supplement 1)

2.1.3 Autoimmune Disease

Dudics S, Venkatesha S, Moudgil K. (2018) The Micro-RNA Expression Profiles of Autoimmune Arthritis Reveal Novel Biomarkers of the Disease and Therapeutic Response. Int. J. Mol. Sci. 19(8):2293.

• Current treatments for rheumatoid arthritis have serious side effects and are only effective in about half of patients, necessitating better biomarkers for predicting and monitoring individual patient responses, and understanding of underlying mechanisms of disease pathogenesis and treatment response.
• In this study, FirePlex miRNA profiling of immune cells and serum in a rat model of rheumatoid arthritis reveals 8 novel biomarkers that point to inflammatory disease pathways. Six of these are indicative of molecular response to celastrol, an anti-inflammatory modulator, revealing novel targets of this drug.
• This is the first study to comprehensively analyze miRNA expression profiles in the context of autoimmune arthritis, providing insight into disease pathogenesis, novel therapeutic targets and potential biomarkers of human disease progression and treatment response. These discoveries open new avenues for improving diagnostic, prognostic and therapeutic tools against RA with non-invasive serum biomarker testing.

Bouyssou J et al. (2018) Profiling of circulating exosomal miRNAs in patients with Waldenstr?m Macroglobulinemia. PLoS ONE 13(10): e0204589

Fernández-Ruiz JC et al. (2018) Analysis of miRNA expression in patients with rheumatoid arthritis during remission and relapse after a 5-year trial of tofacitinib treatment. Int Immunopharmacol.  63:35-42.

2.1.4 Neurology

Zampieri S et al. (2019) Cayenne Pepper Cataplasm “Munari” reduces pain and improves mobility in patients with non-specific chronic low back pain. ?Phys Med & Rehab Res. ?4:1-7.

• The cumulative effects of repeated application of capsaicin may offer a low-cost therapy in the treatment of low back pain.
• Specific miRNA biomarkers were identified via FirePlex multiplex assay as modulating the inflammation and pain signaling in this condition.
• The circulating levels of these miRNA biomarkers were associated with pain and inflammation.
• Capsaicin promoted mechanisms that reduced the levels of the miRNA biomarkers assayed using FirePlex technology and this effect was associated with improved pain, mobility and function in patients. 

Hoss AG et al.  (2015) miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement. BMC Medical Genomics 8(10)

• Huntington’s disease (HD) is a neurodegenerative disease for which there are few prognostic indicators or effective treatments available. MiRNA dysregulation may impact disease progression and severity, and if so, could provide the opportunity to utilize miRNA biomarkers for disease assessment, prognosis, and development of new treatments.
• FirePlex analysis of postmortem human brain tissue revealed differential expression of 75 miRNAs in HD brains. Nine of these associated with the most severe disease pathology, five of which correlated to age of disease onset, including miR-10b-5p as the strongest indicator.
• Biomarkers of interest point to nervous system development processes and transcriptional regulation thereof, identifying critical disease pathways and novel therapeutic targets. If present in blood, urine or other biofluids, these biomarkers may be utilized for diagnostic and prognostic tests to determine disease stage, rate of progression and other important clinical characteristics of HD.

2.1.5 Psychiatry

Lopez JP et al. (2017) MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nature Communications 8, Article number: 15497

• The antiquated trial-and-error approach to antidepressant selection leaves millions of patients suffering for months to years or longer in the search for effective treatments. For nearly 70% of patients their first drug fails, while 30-40% suffer multiple drug failures before finding a successful treatment. Biomarker indicators of drug response are desperately needed to get the right drugs the right patients, within a reasonable timeframe.
• FirePlex analysis of blood samples from patients treated with duloxetine, a serotonin-norepinephrine reuptake inhibitor, revealed 4 miRNA transcripts that were differentially expressed in patients who responded to this treatment. These biomarkers were confirmed in two independent clinical trials, post-mortem human brains, and animal models of depression. Experiments in human neural progenitor cells indicate that these miRNAs regulate dozens of genes within the MAPK/Wnt signaling pathway, many of which are involved in neurotropic factor signaling and neuronal plasticity, proliferation, survival, differentiation and synaptic function.
• These miRNA biomarkers, which are expressed ubiquitously in brain, blood, and other biofluids, could finally provide the critical tools for targeting specific antidepressant drugs to the right patients.  These miRNAs, and the genes that they regulate could be relevant in duloxetine response, and other antidepressant drugs and classes with similar underlying etiologies. Using these biomarkers for antidepressant selection and monitoring could spare millions of patients the time, cost and negative side effects of ineffective treatments on the often long and frustrating road to recovery.
• These biomarkers also point to underlying disease processes and psychiatrically relevant signaling pathways that will help scientists to better understand the disease and design more effective targeted treatments.

Fiori et al. (2017) Investigation of miR-1202, miR-135a, and miR-16 in Major Depressive Disorder and Antidepressant Response. Int J Neuropsychopharmacol.  20(8):619-623.

Lopez JP, Kos A, Turecki G. (2018) Major depression and its treatment: microRNAs as peripheral biomarkers of diagnosis and treatment response. Current Opinion in Psychiatry 31(1): 7-16

2.1.6 Cardiovascular Disease

Shah R et al. (2018) MicroRNAs Associated With Reverse Left Ventricular Remodeling in Humans Identify Pathways of Heart Failure Progression. Circulation: Heart Failure. 11:e004278

• Circulating plasma miRNAs are important indicators of biological processes central to cardiovascular disease and heart failure, including myocardial fibrosis, atherosclerosis, and arrhythmia, pointing to diverse pathological mechanisms like hypertrophy, inflammation, autophagy, and apoptosis.  Multiplex miRNA profiling is essential to understand these complex and diverse factors, to develop better risk assessment tools and targeted treatments for heart disease.
• FirePlex miRNA profiling of blood samples from patients with chronic heart disease before and after treatment reveals a cluster of miRNA transcripts that correlate with improved echocardiograms—a prognostic measure of heart disease-- and reversal of disease.  These miRNAs, involved in autophagy, metabolism and inflammation processes, are dysregulated within heart tissue in mouse and cell culture models, confirming their functional role in disease.
• This study establishes a novel translational paradigm for pathway discovery in heart disease, uncovered novel miRNA, target genes and pathways involved in cardiac injury that could serve as new therapeutic targets. These biomarkers may alert clinicians to early stages of disease before significant damage occurs, and/or select the highest risk patients for more aggressive prevention and surveillance. Already, the biomarker signature identified here is a better predictor of patient response to treatment than current clinical risk parameter standards.

Shah R et al. (2017) Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health: brief report.  Integrative Cardiovascular Physiology and Pathophysiology 313(6): H1162-H1167

2.1.7 Toxicology

Glineur SF et al. (2016) Paving the Route to Plasma miR-208a-3p as an Acute Cardiac Injury Biomarker: Preclinical Rat Data Supports Its Use in Drug Safety Assessment. Toxicological Sciences 149 (1): 89–97    

• Cardiac toxicity is a leading cause of pre-clinical and clinical drug failures and accounts for 45% of drug withdrawals from the market— costing exorbitant amounts of time, money and human lives. This is due to inadequate methods to screen for cardiac injury, with current standards lacking sensitivity and specificity.  Despite significant investments by the pharmaceutical industry, early predictive markers of cardiac safety remain elusive and one of the greatest challenges to drug development success.
• The authors examined a panel of 68 miRNA, all previously reported in human or rodent cardiac injury, in serum from rats treated with the cardiotoxic agents isoproterenol (ISO) or allylamine (AAM). FirePlex analysis revealed 11 potential cardiotoxicity biomarkers, which were all, except one, eliminated as viable candidates for wide fluctuations over time. The remaining candidate, miR-208a-3p, detected cardiac injury severity and magnitude with equivalent or better sensitivity and specificity as the current gold standard.
• miR-208a-3p is a strong candidate for improving drug safety screening with a highly sensitive and cardiac injury specific early biomarker. Encoded by the α-cardiac muscle myosin heavy chain 6 gene, it is exclusively expressed in heart tissue where it plays a vital role in cardiac conduction.  It is also highly conserved between human and rat, providing essential pre-clinical to clinical translational utility.  As a circulating biomarker, it can easily be translated into non-invasive and cost-effective testing in the context of both pre-clinical and clinical trials, ultimately saving extensive amounts of time, money and lives in the quest for new medicines.

Krauskopf J et al. (2017) Serum microRNA signatures as "liquid biopsies" for interrogating hepatotoxic mechanisms and liver pathogenesis in human. PLOS ONE 12(5): e0177928

Glineur SF, et al. (2018) Assessment of a Urinary Kidney MicroRNA Panel as Potential Nephron Segment-Specific Biomarkers of Subacute Renal Toxicity in Preclinical Rat Models. Toxicological Sciences, kfy213   

Gryshkova V et al. (2018) miR-21-5p as a potential biomarker of inflammatory infiltration in the heart upon acute drug-induced cardiac injury in rats. Toxicology Letters 286: 31-38

2.1.8 Others

Liu QY et al. (2018) Inflammation responses in patients with pulmonary tuberculosis in an intensive care unit. Exp Ther Med. 15(3):2719-2726.

Momen-Heravi, Saha B et al. (2015) Increased number of circulating exosomes and their microRNA cargos are potential novel biomarkers in alcoholic hepatitis.  Journal of Translational Medicine 13 (261)

Charles Nelson, Victor Ambros Development 2019 146 

2.2 Molecular publications

Researchers are using FirePlex miRNA profiling technology to discover new molecular and genetic mechanisms of biology.  By providing the tools to expose and examine these new mechanisms in model organisms, FirePlex is helping to open new doors of exploration that could lead to future medical and biotechnology advances.

Edwards et al. (2017) Commercial rodent diets differentially regulate autoimmune glomerulonephritis, epigenetics and microbiota in MRL/lpr mice. Int Immunol.29(6):263-276.

Harden MD, Munger K. (2017) Human papillomavirus 16 E6 and E7 oncoprotein expression alters microRNA expression in extracellular vesicles. Virology 508: 63-69

Hydbring P et al. (2017) Identification of cell cycle-targeting microRNAs through genome-wide screens. Cell Cycle 16(23): 2241–2248. 

Lee H, Zhang D, Zhu Z, Dela Cruz CS, Jin Y. (2016) Epithelial cell-derived microvesicles activate macrophages and promote inflammation via microvesicle-containing microRNAs. Sci Rep 12;6:35250

Nelson C, Ambros V. (2018, preprint) Trans-splicing of the C. elegans let-7 primary transcript developmentally regulates let-7 microRNA biogenesis and let-7 family microRNA activity. bioRxiv

Powell JD, Chen Q, Mason HS. (2016) A cytometry microparticle platform approach for screening tobacco microRNA changes after agrobacterium delivery. Journal of Microbiological Methods 127: 230-235

Ren V et al. (2016). Staufen Negatively Modulates microRNA Activity in Caenorhabditis elegans. G3 (Bethesda) 3;6(5):1227-37.

Ren V, Ambros VR (2015). Caenorhabditis elegans microRNAs of the let-7 family act in innate immune response circuits and confer robust developmental timing against pathogen stress. Proc Natl Acad Sci USA 5;112(18).

Sandhu SK, Fassan M, Volinia S, Lovat F, Balatti V, Pekarsky Y, Croce CM (2013) B-cell malignancies in microRNA Eμ-miR-17~92 transgenic mice, PNAS 5, 110(45), 18208.

Shiu PK, Zhuang JJ, Hunter CP (2014). Assays for direct and indirect effects of C. elegans Endo-siRNAs. Methods Mol. Biol. 1173, 71-87.

Telonis AG et al. (2015). Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies. Oncotarget 22;6(28): 24797-822.

Xu J et al. (2018) Circulating Plasma Extracellular Vesicles from Septic Mice Induce Inflammation via MicroRNA- and TLR7-Dependent Mechanisms. J Immunol. 201 (11)

Yeri A, et al. (2018) Evaluation of commercially available small RNASeq library preparation kits using low input RNA. BMC Genomics 19(1):331.

Zinovyeva AY, Bouasker S, Simard MJ, Hammell CM, Ambros V (2014). Mutations in conserved residues of the C. elegans microRNA Argonaute ALG-1 identify separable functions in ALG-1 miRISC loading and target repression. PLoS Genet. 23, 10(4): e1004286.

Zinovyeva AY, et al. (2015) Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal. PNAS  112 (38) E5271-E5280   

Zou L et al. (2016). Splenic RNA and MicroRNA Mimics Promote Complement Factor B Production and Alternative Pathway Activation via Innate Immune Signaling. J Immunol. 15;196(6):2788-98.

3. Meeting abstracts and reports

Cave M et al.  (2018) Mo1431 - Liquid Liver Biopsy is Consistent with Steatohepatitis in a Residential Cohort Suspected Toxicant Associated Steatohepatitis Related to Polychlorinated Biphenyl Exposures. AASLD Abstracts Gastroenterology 154(6) Supplement 1: S-1204

Dola T, Hughes B, Brady C, Wilder J. (2018) Mo1429 - Hepatitis C Infection Knowledge and Awareness Among Women of Childbearing Age. Gastroenterology 154 (6) Supplement 1: S-1204

Elias KM et al. (2015) A prospective phase 0 study on the effects of anesthetic selection on serum miRNA profiles during primary cytoreductive surgery for suspected ovarian cancer. Gynecologic Oncology 137 (Supplement 1):137     

Elias KM, Frendl G. (2017) Erasmos: Effects of regional analgesia on serum microRNA after oncologic surgery. Clinical Nutrition ESPEN 19: 76 OR07

Emily J, Arentson-Lantz EJ, Lamon S, Fry C, English K, Paddon-Jones D. (2017) Expression of skeletal muscle miRNA are unaltered during 14 days of bed rest but decrease following 7 days of reloading in middle-aged adults. FACEB Journal 31 (Supplement 1) Abstract Number:721.1

Flowers E, Bender M, Fukuoka Y. (2018) Changes in Extracellular Circulating MicroRNAs Are Associated With a Weight Loss Intervention in Filipinos. Circulation 134 (Supplement 1): Abstract 16173.

Gadbil M, Kanava A, Flowers E. (2018) Dietary Patterns and Circulating miRNA Expression in South Asians at Risk for Type 2 Diabetes. Circulation 131(1S) Abstract P301

Hamed A, Brown MS, Szabela M, Slim J. (2018) Mo1428 - Regression of Liver Fibrosis after SVR from Direct-Acting Antivirals (DAAS) in Hepatitis C HIV Co-Infected Patients. Gastroenterology: AASLD Abstracts 154(6) Supplement 1: S-1203-S-1204

Magrey M, Haseeb A, Haqqi T. AB0121 Differentially Expressed MicroRNAs as Candidate Biomarkers for Disease Activity in Ankylosing Spondylitis. Annals of the Rheumatic Diseases 75:938.

Minsart C et al. (2018) Mo1430 - Hepatocyte Release of HMGB1 During Acetaminophen-Induced Liver Injury and Deleterious Feed-Forward Process: Implication of Necroptosis Through TRIF/RIPK3 Axis. AASLD Abstracts Gastroenterology 154(6) Supplement 1:S-1204

Narla A et al. (2015) Unique Circulating MicroRNA Profiles and Endothelial Function in HIV Infection. Journal of the American College of Cardiology 65(10S) A1478 doi: 10.1016/S0735-1097(15)61478-4

Pecorelli N et al.  (2017) Does the risk of postoperative complications affect the adherence to enhanced recovery pathways after pancreaticoduodenectomy? Clinical Nutrition ESPEN 19: p. 76 OR08

Sastry A et al. (2017) The impact of goal directed intraoperative fluid administration during pancreaticoduodenectomy on pancreatic leaks and delayed gastric emptying. Hepato-Pancreato-Billiary Journal of Clinical Nutrition ESPEN 19, Supplement 1:  S27

4. FirePlex Particle Technology Publications

The FirePlex particle technology employs encoded hydrogel particles to provide the highest performance in multiplex biomarker detection. Read more about how this technology works, and how it has transformed miRNA and protein profiling capabilities.

Founding publications

The innovative FirePlex particle technology was conceptualized and created by Dr. Daniel Pregibon. The platform emerged from Pregibon’s PhD thesis at MIT, where he combined photolithography, used to build computer chips, with modern microfluidics techniques to generate customizable microgel particles for biological applications. The ground-breaking new technology promised to revolutionize personalized medicine with fast, easy and affordable biomarker testing; the seminal work was published in the journal Science.

• Pregibon DC, Toner M and Doyle PS (2007). Multifunctional encoded particles for high-throughput biomolecule analysis. Science 315, 1393.

While at MIT, the project was supported by multiple industry partners, as well as MIT’s Deshpande Center for Technological Innovation. Building off the academic success of the platform, Pregibon aimed to commercialize the technology by co-founding Firefly BioWorks, Inc., where he served as President and Chief Technology Officer. The company was awarded multiple grants from the National Cancer Institute and National Institute of Allergies and Infectious Disease at NIH, as well as Massachusetts Life Sciences Center, with a focus on early disease detection. With support from these grants and angel investment, Firefly BioWorks developed and commercialized the first assay capable of detecting circulating miRNA biomarkers directly from crude sample digests.

In 2015, Abcam acquired Firefly Bioworks to extend breadth of content offered on the platform, creating the FirePlex product line. Pregibon continues to impart his expertise, advancing the capabilities and impact of his revolutionary platform as General Manager of Platform Innovation at Abcam.

• Pregibon D. (2014) Leveraging Smart Reagents to Validate Clinical Biomarkers. Seminar, IDEASTREAM: MIT Deshpande Center Symposium 2014
• Perea A, Heinrich B, Austin W, Rafferty C, Camilleri M, To L, Atabakhsh E, Pregibon D. (2018) High-throughput, multiplex quantitation of protein biomarkers using the FirePlex-HT technology platform. Poster, SLAS 2018.   
• Tiny Particles, Big Ideas: Interview with Firefly Bioworks’ Dan Pregibon. Entrepreneurship Review, March 22, 2011.

Others

Appleyard D, Chapin SC, Srinivas R, Doyle PS (2011). Barcoded hydrogel microparticles for protein detection: synthesis, assay and scanning. Nature Protocols 6, 1761.

Chapin SC, Doyle PS (2011) Ultrasensitive multiplexed microRNA quant on encoded gel microparticles using rolling circle amplification. Analytical Chemistry 83, 7179.

Chapin SC, Pregibon DC and Doyle PS (2009). High-throughput flow alignment of barcoded hydrogel microparticles. Lab on a Chip 9, 3100.

Chapin SC, Pregibon DC and Doyle PS (2011). Rapid microRNA profiling on encoded gel microparticles. Agnew Chem Int Ed 50, 2289.

Dendukuri D, Pregibon DC, Collins J, Hatton TA and Doyle PS (2006). Continuous-flow lithography for high-throughput microparticle synthesis. Nature Materials 5, 369.

Helgeson ME, Chapin S, Doyle P. (2011) Hydrogel microparticles from lithographic processes: Novel materials for fundamental and applied colloid science. Curr Opin Colloid Interface Sci. 16(2): 106-7.
 
Markowska A. (2017) A novel method for the isolation of extracellular vesicles and RNA from urine. Journal of Circulating Biomarkers 6

Pregibon DC and Doyle PS (2009). Optimization of encoded hydrogel particles for nucleic acid quantification. Analytical Chemistry 81, 4873.

Royo F et al. (2016) Comparative miRNA Analysis of Urine Extracellular Vesicles Isolated through Five Different Methods.  Cancers 8(12), 112

Tacket MR. (2017) Using FirePlex Particle Technology for Multiplex MicroRNA Profiling Without RNA Purification. Methods Mol Biol. 1654:209-219. doi: 10.1007/978-1-4939-7231-9_14

5. News and Reviews

See what people are saying about FirePlex:

Anfossi et al. (2018) Clinical utility of circulating non-coding RNAs - an update. Nat Rev Clin Oncol.  15(9):541-563. doi: 10.1038/s41571-018-0035-x.

Fiammengo F. (2016) Can nanotechnology improve cancer diagnosis through miRNA detection? Biomarkers in Medicine 11(1) 

Kai K, Dittmar RL, Sen A. (2018) Secretory microRNAs as biomarkers of cancer. Semin Cell Dev Biol. 78:22-36.

Kaufman M, Klinger C, Savelsbergh A. (2017) Functional Genomics: Methods and Protocols. Springer--Methods in Molecular Biology

Khodakov D, Wang C, Zhang DY (2016). Diagnostics based on nucleic acid sequence variant profiling: PCR, hybridization, and NGS approaches. Adv Drug Deliv Rev. S0169-409X(16)30104-1.

Kilic T, Erdem A, Ozsoz M, Carrara S. (2018) microRNA biosensors: Opportunities and challenges among conventional and commercially available techniques. Current Opinion in Colloid & Interface Science 16(2):106-117

Smith-Vikos, T. (2013) Exploiting miRNA’s Potential for Diagnostics and Drugs. Genetic Engineering and Biotechnology News. 33(4): 20, 22-23.

Tacket M, Doran G, Pregibon D. (2015) Multiplex microRNA Profiling from Crude Biofluids. Genetic Engineering and Biotechnology News 35(12)  

• Are you using FirePlex miRNA or immunoassays?
  Send us your FirePlex publications at fireplex@abcam.com to update our list! 

**Note- FirePlex technology was acquired by Abcam in 2015 from Firefly Bioworks. Publications prior to this date refer to the previous proprietary name, “Firefly Bioworks.”

6.  Presentations by the FirePlex Team

Abcam’s FirePlex team develops, optimizes and validates FirePlex products through rigorous scientific studies to ensure the highest-performance capabilities. With an open approach to research and development, we share our data and seek input from colleagues and customers alike to guide the best product design. Our team members are active members of the research community, presenting their work at scientific conferences, research institutes and other venues for scientific review and feedback. We have recently presented posters and seminars at: 

American Association of Cancer Research Annual Meeting

Heinrich B, Doran G, Atabakhsh E, Rafferty C, Pregibon D. (2017) High-throughput, purification-free, multiplexed profiling of circulating miRNA for discovery, validation, and diagnostics. Poster, AACR meeting 2017.

Tackett M, Kelley K, Doran G, Diwan I, Tejada G, Rafferty C, Atabakhsh E, Pregibon D. (2016) Multiplex profiling of circulating miRNAs for biomarker discovery and verification using the FirePlex platform. Poster, AACR meeting 2016.

Society for Laboratory Automation and Screening Annual Meeting

Perea A, Heinrich B, Austin W, Rafferty C, Camilleri M, To L, Atabakhsh E, Pregibon D. (2018) Introducing FirePlex-HT: High-throughput, multiplex immunoassays using FirePlex particle technology.

See Dr. Pregibon’s presentation for LabTube at SLAS 2018

Perea A, Heinrich B, Austin W, Rafferty C, Camilleri M, To L, Atabakhsh E, Pregibon D. (2018) Introducing FirePlex-HT: High-throughput, multiplex immunoassays using FirePlex particle technology. Poster

IDEASTREAM: MIT Deshapande Center Symposium 2014
Pregibon D. (2014) Leveraging Smart Reagents to Validate Clinical Biomarkers. Seminar, IDEASTREAM: MIT Deshapande Center Symposium 2014

FirePlex^? is a registered trademark in the United States and is an unregistered trademark elsewhere.
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FirePlex immunoassays guide

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FirePlex miRNA assay guide

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