Frequently Asked Questions
What is EMPE Diagnostics?
EMPE Diagnostics is a Swedish molecular diagnostics company specializing in tuberculosis (TB) drug resistance testing. Its tests use PLi-RCA technology to detect TB and resistance to TB drugs with high accuracy in a qPCR format. The company’s tagline is “Decoding TB drug resistance”.
Where is EMPE Diagnostics based?
EMPE Diagnostics AB has its corporate headquarters in Stockholm, Sweden. Its Global Operations Center, EMPE Diagnostics Pvt. Ltd, is in Genome Valley, Hyderabad, India, where it designs, develops and manufactures its TB test kits.
When was EMPE Diagnostics founded?
EMPE Diagnostics was founded in 2015.
What problem does EMPE Diagnostics solve?
EMPE Diagnostics makes accurate TB drug resistance testing simple, accessible and affordable, so it can be done at scale in decentralized settings such as district and regional laboratories. Resistance information then reaches clinicians in time to choose the right treatment, rather than after weeks of culture.
Is EMPE Diagnostics' manufacturing certified?
Yes. EMPE Diagnostics’ Hyderabad facility holds ISO certification for the design, development, manufacture and sale of in vitro diagnostic test kits for Mycobacterium tuberculosis.
What is PLi-RCA?
PLi-RCA stands for padlock probe-linked rolling circle amplification. It is EMPE Diagnostics’ technology for detecting specific DNA sequences, including the mutations that make TB resistant to drugs.
How does PLi-RCA work?
A padlock probe is a short DNA strand whose two ends bind side by side on the target sequence. The probe only closes into a circle when both ends match the target exactly; the closed circle is then copied many times by rolling circle amplification, producing a strong signal. A single mismatch stops the probe closing, so no signal is produced.
Why does PLi-RCA give high specificity?
Because a padlock probe must match its target exactly at both ends before it can close and amplify, PLi-RCA distinguishes a resistance mutation from the normal sequence with high specificity. This reduces false resistant results, which can otherwise take patients off the most effective treatment.
Which EMPE tests use PLi-RCA?
mfloDx™ MDR-TB, the upcoming CircuLOK MDR-TB and CircuLOK pre-XDR-TB tests, and EMPE’s pipeline of tests for resistance to bedaquiline, pretomanid and linezolid all use PLi-RCA. CircuLOK TBDx, EMPE’s TB screening test, uses multiplex qPCR.
What is mfloDx™ MDR-TB?
mfloDx™ MDR-TB is EMPE Diagnostics’ test for multidrug-resistant TB. In a single test, it detects Mycobacterium tuberculosis and resistance to the two main first-line drugs, rifampicin and isoniazid, using PLi-RCA technology. It detects 15 targets covering the wild-type sequences and clinically significant resistance mutations in rpoB (codons 516, 526, 531 and 533), katG (codon 315) and the inhA promoter (position −15).
Is mfloDx™ MDR-TB approved?
Yes. mfloDx™ MDR-TB is approved by the Central Drugs Standard Control Organisation (CDSCO), India’s medical device regulator, for use on smear-positive sputum samples.
What samples does mfloDx™ MDR-TB use?
mfloDx™ MDR-TB is approved for smear-positive sputum. Studies in other sample types, including smear-negative and extrapulmonary samples, are under way.
How are mfloDx™ MDR-TB results read?
mfloDx™ MDR-TB results are read by eye, without the need for a dedicated reader instrument.
How long does mfloDx™ MDR-TB take?
mfloDx™ MDR-TB takes about 3 hours from sample to result.
Does mfloDx™ MDR-TB need a culture step?
No. mfloDx™ MDR-TB runs directly on a patient’s sputum sample after standard NALC-NaOH decontamination, without any preceding culture.
What equipment does mfloDx™ MDR-TB need?
mfloDx™ MDR-TB is designed for minimal, standard laboratory equipment: a thermal cycler, a heat block, a microcentrifuge and a vortex mixer. Results are developed on a lateral flow cassette and read visually, so no dedicated reader instrument is needed. Samples are handled in a class II biosafety cabinet, as for all TB sputum processing.
What is the limit of detection of mfloDx™ MDR-TB?
In spiked sputum, the limit of detection of mfloDx™ MDR-TB is about 650 CFU/ml for TB detection, 517 CFU/ml for katG and inhA, and 563 CFU/ml for rpoB, equivalent to about 2.5 to 3.2 CFU per reaction.
Does mfloDx™ MDR-TB cross-react with non-tuberculous mycobacteria?
No cross-reactivity was found. mfloDx™ MDR-TB detects the Mycobacterium tuberculosis complex (M. tuberculosis, M. africanum, M. bovis, M. microti and M. canetti), and gave no signal with 11 non-tuberculous mycobacteria tested, including M. avium, M. intracellulare, M. kansasii, M. abscessus and M. fortuitum.
What quality controls are built into mfloDx™ MDR-TB?
Each mfloDx™ MDR-TB test has two built-in controls. An internal control confirms the whole process worked, from sample preparation to signal development, guarding against false negatives. A hybridisation control confirms that the visualisation reagents and the lateral flow cassette performed correctly.
How is mfloDx™ MDR-TB stored?
The mfloDx™ MDR-TB amplification kit (AMP) is stored at −25 °C to −16 °C, and the visualisation kit (VIS) at 2 °C to 8 °C.
How does mfloDx™ MDR-TB compare with line probe assays?
Like first-line line probe assays (LPAs), mfloDx™ MDR-TB detects TB together with rifampicin and isoniazid resistance from a single sample. The key difference is the samples each can test directly. The WHO recommends first-line LPAs only for smear-positive sputum or cultured isolates, and does not recommend them for direct testing of smear-negative sputum (WHO). Smear microscopy typically detects TB only above about 5,000–10,000 bacilli per ml (aidsmap), so smear-negative samples must first be cultured, which can add 3 to 4 weeks. mfloDx™ MDR-TB has a limit of detection of about 650 CFU/ml, well below the smear-positive threshold, and runs directly on decontaminated sputum without culture. It gives results in about 3 hours and is read visually. mfloDx™ MDR-TB is currently approved for smear-positive sputum, with studies in smear-negative samples under way.
What is CircuLOK TBDx?
CircuLOK TBDx is EMPE Diagnostics’ molecular test for TB screening. It is a lyophilised multiplex qPCR test that detects Mycobacterium tuberculosis using four gene targets, and runs on open qPCR instruments.
Does CircuLOK TBDx detect drug resistance?
No. CircuLOK TBDx detects TB only. Positive samples are reflexed to EMPE’s resistance tests for rifampicin, isoniazid and, with CircuLOK pre-XDR-TB, fluoroquinolones.
Why does CircuLOK TBDx use four gene targets?
CircuLOK TBDx amplifies four separate TB gene targets. Detecting several targets makes the test more reliable, because a positive result does not depend on a single region of the TB genome.
How long does CircuLOK TBDx take and how many samples can it run?
CircuLOK TBDx takes about 75 minutes and runs anywhere from 1 to 96 samples per run, with a three-step workflow.
Why is CircuLOK TBDx lyophilised?
CircuLOK TBDx reagents are lyophilised (freeze-dried), which simplifies storage and transport and reduces the risk of contamination during set-up. CircuLOK TBDx is stored between 4 °C and 25 °C.
When will CircuLOK TBDx be available?
CircuLOK TBDx will soon be available as an early access opportunity for laboratories. Full regulatory approval is expected in 2027.
What are CircuLOK MDR-TB and CircuLOK pre-XDR-TB?
CircuLOK MDR-TB and CircuLOK pre-XDR-TB are EMPE Diagnostics’ upcoming TB drug resistance tests in a qPCR format. CircuLOK MDR-TB detects resistance to rifampicin and isoniazid; CircuLOK pre-XDR-TB adds resistance to fluoroquinolones.
What technology do the CircuLOK resistance tests use?
The CircuLOK resistance tests use EMPE’s PLi-RCA technology, read out on open qPCR instruments. This combines the high specificity of padlock probes with a format that laboratories already know.
Can laboratories choose which resistance tests to run?
Yes. Laboratories can choose the resistance coverage that fits their patients and budget, from rifampicin and isoniazid with CircuLOK MDR-TB to fluoroquinolones with CircuLOK pre-XDR-TB, and expand as their needs grow.
When will the CircuLOK resistance tests be available?
CircuLOK MDR-TB and CircuLOK pre-XDR-TB will be available to laboratories for evaluation towards the end of 2026.
Is EMPE Diagnostics developing tests for bedaquiline, pretomanid and linezolid resistance?
Yes. EMPE Diagnostics is developing PLi-RCA tests for resistance to bedaquiline, pretomanid and linezolid, the core drugs of the WHO-recommended BPaLM regimen for drug-resistant TB. These tests are in development and not yet available.
Why does testing for BPaLM drug resistance matter?
BPaLM has shortened treatment for drug-resistant TB to six months, but resistance to bedaquiline is already being reported worldwide. Without accessible testing, resistance is often found only after treatment fails. EMPE’s aim is for resistance testing to keep pace with the regimens being rolled out.
Which mutations will EMPE's BPaLM tests detect?
EMPE’s BPaLM tests are designed to detect only mutations with strong evidence of resistance, rather than every variant. This makes them rule-in tests: a resistant result can be acted on with confidence, without the false positives that mutations of uncertain significance can cause. As new resistance mutations are confirmed, the panels can be extended.
Why not sequence the whole genome to test for BPaLM resistance?
For bedaquiline, pretomanid and linezolid, many mutations found by sequencing are still of uncertain significance, so sequencing can miss resistance or over-call it. Sequencing is also expensive and technically demanding to carry out: it needs culture, specialist laboratories, highly trained staff and bioinformatics. That makes it very difficult to scale to the district and regional laboratories where most patients are diagnosed. Sequencing remains essential for surveillance and discovering new resistance mechanisms.
Who might use EMPE's BPaLM tests first?
EMPE expects early interest from countries already using BPaLM at scale, through early access opportunities.
How accurate are EMPE Diagnostics' tests?
EMPE Diagnostics measures the accuracy of its tests against culture-based drug susceptibility testing, the reference standard for TB drug resistance. In a performance evaluation at ICMR-NIRT, Chennai, mfloDx™ MDR-TB showed 100% sensitivity for detecting TB and for detecting rifampicin and isoniazid resistance in smear-positive sputum, with 100% positive predictive value and diagnostic accuracy. Across pooled smear-positive and smear-negative sputum in the same evaluation, it showed 98% diagnostic accuracy, 97% sensitivity, 100% specificity, 100% positive predictive value and 91% negative predictive value. mfloDx™ MDR-TB is currently approved for smear-positive sputum; further studies to extend its use, including to smear-negative samples, are under way.
What reference standard does EMPE Diagnostics use?
EMPE Diagnostics uses culture, phenotypic drug susceptibility testing, as its gold standard. Culture shows whether TB bacteria actually grow in the presence of a drug, which is the most direct measure of resistance.
Why does EMPE Diagnostics benchmark its tests against line probe assays?
Line probe assays (LPAs) are the established molecular method for TB drug resistance testing in reference and intermediate laboratories, and are recommended by the WHO. EMPE benchmarks against LPAs because they are the method its tests are designed to complement or replace in those laboratories.
Do EMPE's tests need a culture step first?
No. All EMPE Diagnostics tests run directly on decontaminated sputum, without any preceding culture.
Why does specificity matter in TB drug resistance testing?
A false resistant result can move a patient off the most effective regimen onto treatment that is longer, more toxic or less likely to work. EMPE’s PLi-RCA technology is designed for high specificity, so resistant results can be trusted.
Which laboratories can use EMPE Diagnostics' tests?
EMPE Diagnostics’ qPCR tests are designed for laboratories with open real-time PCR (qPCR) instruments, including district and regional laboratories. This enables testing at scale in decentralised settings, closer to where patients are diagnosed.
What instruments do EMPE Diagnostics' tests need?
EMPE’s CircuLOK tests run on open qPCR instruments, which are easy to source and cost much less than closed diagnostic platforms. There is no closed platform to buy into.
Why use open qPCR systems rather than a closed platform?
Open qPCR systems are widely available, cost less than closed systems, and can run many other tests. A laboratory equipped for EMPE’s TB tests can also respond to outbreaks of other infectious diseases, such as Ebola, chikungunya or Lassa fever, using the same instruments.
Can EMPE's tests handle high sample volumes?
Yes. CircuLOK TBDx runs from 1 to 96 samples in about 75 minutes, so a single laboratory can screen high volumes in a working day while still running small batches when needed.
How much training do EMPE's tests need?
Laboratory staff need 1 to 2 days of training to run EMPE Diagnostics’ tests.
Which EMPE Diagnostics tests are available now?
mfloDx™ MDR-TB is approved by CDSCO in India. CircuLOK TBDx will soon be available as an early access opportunity, with full regulatory approval expected in 2027. CircuLOK MDR-TB and CircuLOK pre-XDR-TB will be available to laboratories for evaluation towards the end of 2026. The BPaLM resistance tests are in development.
What is an early access opportunity?
An early access opportunity lets laboratories start using an EMPE Diagnostics test before its full regulatory approval, to evaluate it and build experience with it.
Where are EMPE Diagnostics' tests available?
EMPE Diagnostics serves India directly and is building a distributor network in Latin America, Africa and APAC
How can a laboratory evaluate an EMPE Diagnostics test?
Laboratories can request an evaluation kit and an on-site demonstration through the EMPE Diagnostics website.
Does EMPE Diagnostics work with distributors and partners?
Yes. EMPE Diagnostics partners with distributors, laboratory networks and national TB programmes to make its tests available. Organisations interested in partnering can contact the company through empediagnostics.com.