About

TruCulture

A Whole Blood Collection and Culture Tube for Standardized Immunophenotyping Procedures

TruCulture tubes are designed to capture immune cell activity at the time and place of sample collection, thereby minimizing the bias and variability introduced by sample shipping and manipulation. These revolutionary tubes consist of an integrated whole-blood collection and leukocyte culture system that is reliable, simple to use and does not require specialized laboratory equipment. TruCulture enables researchers to reproducibly ascertain information about immune responses to stress or stimulation, including responses to novel therapeutics. The ex vivo TruCulture procedure preserves physiological cellular interactions to more accurately reflect the complexities of the human immune system, bringing added value to immune monitoring in clinical trials.

How TruCulture Works:

TruCulture tubes simplify and optimize the procedure for immune stimulation, assuring standardization and harmonization of results across different laboratories.

Collect

TruCulture tubes are pre-loaded with cell culture media and your choice of stimulant. The tubes are sent frozen and shipped directly to the collection site.

1mL of blood is drawn directly into the tube.

Incubate

The tubes are incubated in dry heat blocks at 37°C for at least 30 minutes and up to 48 hours, depending on the application.

After incubation, an easy to use mechanical separator is inserted to stop the reaction.

Analyze

The frozen tubes should be sent to Myriad RBM’s testing laboratory for analysis of secreted cytokines and chemokines.

The tubes are also compatible with flow cytometry and gene expression analysis.

TruCulture Tube Components

Applications

TruCulture has been utilized as a whole-blood stimulation system by researchers and drug developers in several fields to reliably measure immune response for the following applications.

  • Pharmacodynamics (including dose response)
  • Functional immune cell analysis
  • Disease characterization
  • Patient stratification
  • Genotype – to – Phenotype association studies

In one pertinent example, our partner, The Institut Pasteur, demonstrated the indispensable benefits of TruCulture in The Milieu Intérieur (“Environment Within”) project. Briefly, the Milieu Intérieur project is working to establish the determinants of a healthy immune response by identifying the genetic, epigenetic and environmental factors that contribute to the observed heterogeneity of immune responses. The challenge of the project is to establish the boundaries of a healthy immune response, and to that end, the Milieu Intérieur Project recruited 1,000 healthy individuals stratified across age (five-decades of life from age 20 – 69), and gender (1:1 gender ratio). TruCulture tubes were an integral part of the Milieu Intérieur clinical study, used as a standardized method for monitoring human response to immune stimulation.

To define the boundaries of a healthy immune response, The Milieu Intérieur project combined the use of TruCulture whole blood culture system with the use of stimuli to define the protein signatures induced by (i) medically relevant bacteria, fungi and viruses; (ii) agonists specific for defined host sensors; (iii) clinically employed cytokines; and (iv) activators of T cell immunity.

Visit The Milieu Intérieur website for more information on the project, publications, protocols, and data exploration.

View an Overview of The Milieu Intérieur Project:

Publications

View Peer-Reviewed Publications Citing TruCulture

Bibliography

TruCulture

2018

A decade of research on the 17q12-21 asthma locus: Piecing together the puzzle (2018) Stein MM, Thempson EE, Schoettler N, Helling BA, Magnaye KM, Stanhope C, Igartua C, Morin A, Washinton C, Nicolae D, Bonnelykke K, Ober C J Allergy Clin Immunol 2018
 
Therapy Indications
TruCulture
Pulmonary
 
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2017

Effects of Traumeel (Tr14) on recovery and inflammatory immune response after repeated bouts of exercise: a double-blind RCT. (2017) Muders K, Pilat C, Deuster V, Frech T, Krüger K, Pons-Kuhnemann J, Mooren FC Eur J Appl Physiol.
Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy (2017) Gnjatic S, Bronte V, Brunet LR, Butler MO, Disis ML, Galon J, Hakansson LG, Hanks BA, Karanikas V, Khleif SN, Kirkwood JM, Miller LD, Schendel DJ, Tanneau I, Wigginton JM and Butterfield LH J Immunother Cancer
 
Therapy Indications
Cancer
Immuno-oncology
TruCulture
 
Effect of DHA supplementation on oxylipin levels in plasma and immune cell stimulated blood. (2017) Schuchardt JP, Ostermann AI, Stork L, Fritzsch S, Kohrs H, Greupner T, Hahn A, Schebb NH Prostaglandins Leukot Essent Fatty Acids
The REAnimation Low Immune Status Markers (REALISM) project: a protocol for broad characterisation and follow-up of injury-induced immunosuppression in intensive care unit (ICU) critically ill patients (2017) Rol ML, Venet F, Rimmele T, Moucadel V, Cortez P, Quemeneur L, Gardiner D, Griffiths A, Pachot A, Textoris J, Monneret G, On behalf of the REALISM study group BMJ Open
Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study (2017) Duffy D, Rouilly V, Braudeau C, Corbière V, Djebali R, Ungeheuer MN, Josien R, LaBrie ST, Lantz O, Louis D, Martinez-Caceres E, Mascart F, Ruiz de Morales JG, Ottone C, Redjah L, Guen N, Savenay A, Schmolz M, Toubert A, Albert ML Clin Immunol
Dietary Buglossoides Arvensis Oil Increases Circulating n-3 Ployunsaturated Fatty Acids in a Dose Dependent Manner and Enhances Lipopolysaccharide-Stimulated Whole Blood Interleukin-10-A Randomized Placebo-Controlled Trial. (2017) Lefort N, LeBlanc R, Surette M Nutrients
 
Therapy Indications
Cytokines/Chemokine
TruCulture
 
Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges. (2017) Piasecka B, Duffy D, Urrutia A, Quach H, Patin E, Posseme C, Bergstedt J, Charbit B, Rouilly V, MacPherson CR, Hasan M, Albaud B, Gentien D, Fellay J, Albert ML, Quintana-Murci L, Milieu Intérieur Consortium Proc Natl Acad Sci U S A
Impact of Maternal antibodies and infant gut microbiota on the immunogenicity of rotacirus vaccines in African, Indian, and European infants: protocol for a prospective cohort study. (2017) Sindhu KN, Cunliffe N, Peak M, Turner M, Darby A, Grassly N, Gordon M, Dube Q, Babji S, Praharaj I, Verghese V, Iturriza-Gomara M, Kang G BMJ
Immunodepression after CPB: Cytokine dynamics and clinics after pediatric cardiac surgery – A prospective trial (2017) Justus G, Walker C, Rosenthal LM, Berger F, Miera O, Schmitt KR Cytokine
Altered Immune Activation and IL-23 Signaling in Response to Candida albicans in Autoimmune Polyendocrine Syndrome Type 1 (2017) Bruserud O, Bratland E, Hellesen A, Delaleu N, Reikvam H, Oftedal BE, and Wolff A Front Immunol.
Randomized clinical study of safety, pharmacokinetics, andpharmacodynamics of RIPK1 inhibitor GSK2982772 in healthyvolunteers (2017) Weisel K, Scott NE, Tompson DJ, Votta BJ, Madhavan S, Povey K, Wolstenholme A, Simeoni M, Rudo T, Richards-Peterson L, Sahota T, Wang JE, Lich J, Finger J, Verticelli A, Reilly M, Gough PJ, Harris PA, Bertin J, Wang M Pharmacol Res Perspect.
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2016

Standardized Whole-Blood Transcriptional Profiling Enables the Deconvolution of Complex Induced Immune Responses (2016) Urrutia A, Duffy D, Rouilly V, Posseme C, Djebali R, Illanes G, Libri V, Albaud B, Gentien D, Piasecka B, Hasan M, Fontes M, Quintana-Murci L, Albert Matthew l, Abel L, Alcover A, Astrom K, Bousso P, Bruhns P, Cumano A, Demangel C, Deriano L, Di santo J, Dromer F, Eberl G, Enninga J, Fellay J, Freitas A, Gelpi O, Gomperts-Boneca I, Hercberg S, Lantz O, Leclerc C, Mouquet H, Pellegrini S, Pol S, Rogge L, Sakuntabhai A, Schwartz O, Schwikowski B, Shorte S, Soumelis V, Tangy F, Tartour E, Toubert A, Ungeheuer M-N, Quintana-Murci L, Albert Matthew Cell Reports
 
Therapy Indications
TruCulture
 
Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity (2016) Dietsch GN, Lu H, Yang Y, Morishima C, Chow LQ, Disis ML, Hershberg RM PLoS ONE
 
Therapy Indications
Cancer
TruCulture
 
Biological stress systems, adverse life events and the improvement of chronic multi-site musculoskeletal pain across a 6-year follow-up. (2016) Generaal E, Vogelzangs N, Macfarlane GJ, Geenen R, Smit JH, de Geus EJ, Dekker J, Penninx BW. J Pain
 
Therapy Indications
TruCulture
 
Immune Monitoring Technology Primer: Immunoprofiling of Antigen-Stimulated Blood (2016) Brunet LR, LaBrie S, Hagemann T Journal for Immunotherapy of Cancer
Social status alters immune regulation and response to infection in macaques (2016) Snyder-Mackler N, Sanz J, Kohn JN, Brinkworth JF, Morrow S, Shaver AO, Grenier JC, Pique-Regi R, Johnson ZP, Wilson ME, Barreiro LB, Tung J Science
Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture-Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial (2016) Lerman I, Hauger R, Sorkin L, Proudfoot J, Davis B, Huang A, Lam K, Simon B, Baker DG Neuromodulation: Technology at the Neural Interface
Exercise-induced cytokine changes in antigen stimulated whole-blood cultures compared to serum (2016) Pilat C, Krüger K, Frech T, Mooren FC J Immunol Methods.
Vagus Nerve Stimulation Inhibits Cytokine Production and Attenuates Disease Severity in Rheumatoid Arthritis (2016) Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP PNAS
Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT (2016) Muders K, Pilat C, Deuster V, Frech T, Kruger K, Pons-Kuhnemann J, Mooren F-C Mediators of Inflammation
Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children (2016) Stein MM, Hrusch CL, Gozdz J, Igartua C, Pivniouk V, Murray SE, Ledford JG, Marques Dos Santos M, Anderson RL, Metwali N, Neilson JW, Maier RM, Gilbert JA, Holbreich M, Thorne PS, Martinez FD, Von Mutius E, Vercelli D, Ober C, Sperling AI New England Journal of Medicine
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2015

Immune cell profiling to guide therapeutic decisions in rheumatic diseases. (2015) Ermann J, Rao DA, Teslovich NC, Brenner MB, Raychaudhuri S. Nat Rev Rheumatol. 2015 Jun 2. doi: 10.1038/nrrheum.2015.71. [Epub ahead of print]
Specificity of human anti-variable heavy (VH) chain autoantibodies and impact on the design and clinical testing of a VH domain antibody antagonist of TNF-a receptor 1 (2015) Cordy JC, Morley PJ, Wright TJ, Birchler MA, Lewis AP, Emmins R, Chen YZ, Powley WM, Bareille PJ, Wilson R, Tonkyn J, Bayliffe AI, Lazaar AL. Clin Exp Immunol.
The Milieu Intérieur Study — an Integrative Approach for Study of Human Immunological Variance (2015) Thomas S, Rouilly V, Patin E, Alanio C, Dubois A, Delval C, Marquier L-G, Fauchoux N, Sayegrih S, Vray M, Duffy D, Quintana-Murci L, Albert ML, Abel L, Alcover A, Bousso P, Bruhns P, Cumano A, Daëron M, Delval C, Demangel C, Deriano L, Di Santo J, Dromer F, Eberl G, Enninga J, Freitas A, Gelpi O, Gomperts-Boneca I, Hercberg S, Lantz O, Leclerc C, Mouquet H, Pellegrini S, Pol S, Rogge L, Sakuntabhai A, Schwartz O, Schwikowski B, Shorte S, Soumelis V, Tangy F, Tartour E, Toubert A, Ungeheuer M-N, Quintana-Murci L, Albert ML Clinical Immunology
Identification of circulatory biomarkers from clinical trial samples (2015) Brunet LR, Bodman-Smith K, Bodman-Smith M, Kassam Z, Dalgleish A, LaBrie S and Hagemann T J Immunother Cancer
Late Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337) (2015) Dietsch GN, Randall TD, Gottardo R, Northfelt DW, Ramanathan RK, Cohen PA, Manjarrez KL, Newkirk M, Bryan JK, Hershberg RM Clinical Cancer Research
Cd4+ T-Cell Profiles and Peripheral Blood Ex-Vivo Responses to T-Cell Directed Stimulation Delineate Copd Phenotypes (2015) Roberts MEPH, Brandon W.; Brohawn, Philip; Pilataxi, Fernanda; Guo, Xiang; Kuziora, Michael; Bowler, Russell P.; White, Wendy I. Chronic Obstructive Pulmonary Diseases
 
Therapy Indications
TruCulture
 
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2014

Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats. (2014) Erdely A, Antonini JM, Young SH, Kashon ML, Gu JK, Hulderman T, Salmen R, Meighan T, Roberts JR, Zeidler-Erdely PC. Part Fibre Toxicol. 2014 Aug 15;11:34. doi: 10.1186/s12989-014-0034-8.
 
Therapy Indications
TruCulture
 
Exploring effects of a natural combination medicine on exercise-induced inflammatory immune response: A double-blind RCT (2014) Pilat C, Frech T, Wagner A, Krüger K, Hillebrecht A, Pons-Kühnemann J, Scheibelhut C, Bödeker RH, Mooren FC Scand J Med Sci Sports. 2014 Jun 12
Functional Analysis via Standardized Whole-Blood Stimulation Systems Defines the Boundaries of a Healthy Immune Response to Complex Stimuli (2014) Duffy D, Rouilly V, Libri V, Hasan M, Beitz B, David M, Urrutia A, Bisiaux A, LaBrie ST, Dubois A, Boneca IG, Delval C, Thomas S, Rogge L, Schmolz M, Quintana-Murci L, Albert ML Immunity Volume 40, Issue 3, 20 March 2014, Pages 436–450
Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized, Placebo-Controlled, Double-Blind Clinical Trial in Healthy Volunteers (2014) Schmolz M, März RW, Schaudt M, Schaudt C, Lauster C Food and Nutrition Sciences, Vol. 5 No. 4, 2014, pp. 341-350
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2013

Placebo-Controlled Randomized Clinical Trial on the Immunomodulating Activities of Low- and High-Dose Bromelain after Oral Administration – New Evidence on the Antiinflammatory Mode of Action of Bromelain (2013) Müller S, März R, Schmolz M, Drewelow B, Eschmann K, Meiser P Phytotherapy Research
Identification of a molecular profile associated with immune status in first onset schizophrenia patients (2013) Herberth M, Rahmoune H, Schwarz E, Koethe D, Harris LW, Kranaster L, Witt SH, Spain M, Barnes A, Schmolz M, Leweke MF, Guest PC, Bahn S Clin Schizophr Relat Psychoses
Autoantibodies to Variable Heavy (VH) Chain Ig Sequences in Humans Impact the Safety and Clinical Pharmacology of a VH Domain Antibody Antagonist of TNF-a Receptor 1 (2013) Holland MC, Wurthner JU, Morley PJ, Birchler MA, Lambert J, Albayaty M, Serone AP, Wilson R, Chen Y, Forrest RM, Cordy JC, Lipson DA, Bayliffe AI Journal of Clinical Immunology, July 2013
 
Therapy Indications
Cytokines/Chemokine
TruCulture
 
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2012

Intraindividual long term stability and response corridors of cytokines in healthy volunteers detected by a standardized whole-blood culture system for bed-side application (2012) Mueller SC, März R, Schmolz M, Drewelow B BMC Med Res Methodol. 2012 Aug 1;12(1):112
 
Therapy Indications
Cytokines/Chemokine
TruCulture
 
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2011

Discrimination of agonist and antagonist forms of CXCL10 in biologic samples (2011) Casrouge A, Bisiaux A, Stephen L, Schmolz M, Mapes J, Pfister C, Pol S, Mallet V, Albert ML Clin Exp Immunol. 2012 Jan;167(1):137-48
Phagocytosis and digestion of pH-sensitive fluorescent dye (Eos-FP) transfected E. coli in whole blood assays from patients with severe sepsis and septic shock (2011) Schreiner L, Huber-Lang M, Weiss ME, Hohmann H, Schmolz M, Schneider EM J Cell Commun Signal. 2011 Jun;5(2):135-44
Effects of Echinaforce® treatment on ex vivo-stimulated blood cells (2011) Ritchie MR, Gertsch J, Klein P, Schoop R Phytomedicine. 2011 Jul 15;18(10):826-31
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2010

Synthetic Ligands Against TLR2-9 in TruCulture - whole blood assays distinguish clinical stages of SIRS (trauma) and sepsis (2010) Bindja J, Weiss ME, Schmolz M, Stein GM, Mapes J, Schneiderhan-Marra N, Joos TO, Schneider EM TSIS Mar 9-13th
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2008

"Host Tissue Damage" Signal ATP Impairs IL-12 and IFNgamma Secretion in LPS Stimulated Whole Human Blood. (2008) Nalos M, Huang S, Sluyter R, Khan A, Santner-Nanan B, Nanan R, McLean AS Intensive Care Med 34: 1891-1897.
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2004

Validation of a new highly standardised, lab-independent whole-blood leukocyte function assay for clinical trials (ILCS). (2004) Schmolz M, Hurst TL, Bailey DM, Powell JR, Forsey RJ, Thompson JM, Williams C, Pawelec G Exp Gerontol 39: 667-671.
 
Therapy Indications
Miscellaneous
TruCulture
 

Case Studies

Milieu Intérieur: Personalized Immune Response Monitoring

“We hope to advance the promise of personalized medicine with functional biomarkers.”
Dr. Matthew Albert, Director of the Department of Immunology; Co-Director and Founder of the Center for Human Immunology at Institut Pasteur; Adjunct Faculty at Cochin Hospital

Applications of TruCulture in Chronic infection

“What makes our project unique is our ability to induce standardized immune responses…possible because of the reproducibility of the TruCulture system.”
Dr. Darragh Duffy, Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur

Statistical Analysis and Mathematical Modeling of Data Derived from TruCulture

“[Using TruCulture] we get high quality data with very little variation.”
Pr. Magnus Fontes, Director of the International Group for Data Analysis, Institut Pasteur

Stimulants

Part # Description Type
782-001086 Null TruCulture Tubes (TC Tubes Null) Control
782-001291 NegCo Control
782-001219 TNF-alpha (TC Tubes TNFa 10ng/ml) Cytokine
782-001224 Intron A, IFN-alpha (TC Tubes IFNa) Cytokine
782-001277 Interferon beta (TC Tubes IFN-beta) Cytokine
782-001278 Interleukin-1beta + tumor necrosis factor-alpha (TC Tubes IL-1b+TNFa) Cytokine
782-001279 Intron A + anti-CD3 + anti-CD28 (TC Tubes IFNa+CD3+CD28) Cytokine
782-001225 Intron A + LPS-EB high (TC Tubes IFNa+LPS-EB) Cytokine / TLR4 Ligand
782-001272 Adenosine Triphosphate + Lipopolysaccharide, high concentration (TC Tubes ATP+LPS-EB) NLRP3 Inflammasome / TLR4 Ligand
782-001273 Lauroyl-γ-D-glutamyl-meso-diaminopimelic acid (TC Tubes C12-iE-DAP) NOD Ligand
782-001280 Lipoarabinomannan from M. smegmatis (TC Tube LAM-MS) NOD Ligand
782-001124 SEB TruCulture Tubes (TC Tubes SEB) T-Cell
782-001125 CD3/CD28 TruCulture Tubes (TC Tubes CD3+CD28) T-Cell
782-001126 SEB/CD28 TruCulture Tubes (TC Tubes SEB+CD28) T-Cell
782-001202 CD3 TruCulture Tubes (TC Tubes CD3) T-Cell
782-001259 Zymosan TruCulture Tubes (TC Tubes ZYM) TLR2 Ligand
782-001274 Fibroblast-stimulating Lipopeptide (TC Tubes FSL-1) TLR2 Ligand
782-001275 HKEB (TC Tubes HKEB) TLR2 Ligand
782-001276 HKLR (TC Tubes HKLR) TLR2 Ligand
782-001282 Polyinosinic:polycytidylic acid (TC Tube Poly I:C) TLR3 Ligand
782-001087 LPS TruCulture Tubes (TC Tubes LPS) TLR4 Ligand
782-001089 LPS+SEB TruCulture Tubes (TC Tubes LPS+SEB) TLR4 Ligand / T-Cell
782-001264 Resiquimod R848 (TC Tubes R848) TLR7/8 Ligand
782-001269 Gardiquimod (TC Tubes GDQ) TLR7/8 Ligand
782-001281 Class A CpG oligonucleotide + LPS-EB high (TC Tube ODN2216+LPS-EB) TLR9 Ligand

If the stimulant you’d like to use in our TruCulture tubes is not listed, please fill out this form to request it. One of our experts will contact you to discuss the feasibility of your request. Thank you for your interest in TruCulture.

Request a Stimulant 

Analysis

Myriad RBM provides quantitative measurement of immune related proteins from TruCulture supernatants. Whether your specific application requires a broad range or a focused set of analytes, Myriad RBM’s panels are designed to meet your needs.

TruCulture® OptiMAP is an immunoassay testing panel validated and optimized to quantify the effect of TruCulture stimulations.  It is a cost-effective test comprised of 13 biomarkers that captures the diversity of responses to microbial, viral, and T cell stimulants.

OptiMAP Biomarkers

Click or mouse over biomarkers for more information. Analytes included in this MAP are subject to change.
Don't See Your Biomarker? Request It »
1. Epithelial-Derived Neutrophil-Activating Protein 782. Granulocyte-Macrophage Colony-Stimulating Factor
3. Interferon gamma4. Interleukin-1 beta
5. Interleukin-106. Interleukin-12 Subunit p70
7. Interleukin-138. Interleukin-17
9. Interleukin-210. Interleukin-23
11. Interleukin-612. Interleukin-8
13. Tumor Necrosis Factor alpha
MAP Volume Required
OptiMAP v. 1.0 TruCulture Supernatant 100 μL

OptiMAP Design

A total of 106 immune-related biomarkers were tested on TruCulture samples taken from healthy subjects. A careful selection of the key stimulants listed below were used to monitor a wide range of immune response pathways.  From the 106 candidate biomarkers, we selected a subset of 13 assays that were useful in distinguishing responses to individual stimuli while also revealing population variances.

Microbial stimulants: LPS, IL-1β, TNF-α, BCG, HK C. albicans, HK E. coli, HK S. aureus

Viral stimulants: Poly IC, R848, IFN- α/β

T cell stimulants:  SEB, anti-CD3/CD28

Principle component analysis of 25 normal subjects each tested with 12 TruCulture stimuli and responses monitored with either 106 protein biomarkers or an optimized panel of 13 protein biomarkers. Both analyses show a similar ability to segregate responses by the various stimuli, indicating the utility and efficiency of the OptiMAP panel.

 

For a more comprehensive understanding of functional immune cell activity, TruCulture supernatant can be tested on any of our Human MAP products. The tubes are also compatible with flow cytometry and gene expression analysis.

Multiplex immunoassay analysis of TruCulture supernatants is conducted in our CLIA-certified testing laboratory.

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Co-Developing new tubes

To co-develop Truculture tubes of interest, please contact us.
Myriad RBM can evaluate your stimuli of interest for sterility, solubility, dose response, short and long-term stability, and reproducibility.

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