A Biosensor and Method for Disease Diagnosis Based on Magnetic Resonance Relaxometry

Technology #14651-15161-17520

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(a) A train
 of radiofrequency pulses at the resonance frequency of 21.65 MHz 
with respect to the proton nuclei spins is applied at an inter-echo 
time interval, techo. (b) The transverse 
relaxation rate, R2, is a function of the parasite load present in the sample.
 Owing to the presence of highly paramagnetic hemozoin crystallites formed
 in the intra-erythrocyte cycle of the Plasmodium spp. infection, proton
spin-spin interaction in iRBCs dephases much faster than the one in uninfected
 RBCs.Schematic illustration of the MRR 
system, which consists of a portable permanent magnet that provides a strong polarizing
 magnetic field and a home-built radiofrequency (RF) detection probe. The biosensor is connected to an RF spectrometer, which acts as a transmitter and receiver of the RF signal. A microcentrifuge is used to separate the plasma from the RBC- and iRBC-containing pellet is placed inside a microcapillary tube. The microcapillary tube is then slotted into the RF detection probe.
Categories
Inventors
Professor Jongyoon Han
Electrical Engineering - Computer Science, MIT
External Link (www.rle.mit.edu)
Weng Kung Peng
Singapore-MIT Alliance for Research & Technology
Lan Chen
Aeronautics & Astronautics, Nanyang Technological University
Tze Ping Loh
National University Hospital
Managed By
Michelle Hunt
MIT Technology Licensing Officer
Patent Protection

Biosensor, palm-sized device and method based on magnetic resonance relaxometry

US Patent Pending US 2015-0177348

Micro Magnetic Resonance Relaxometry

PCT Patent Application Filed

Micro Magnetic Resonance Relaxometry

US Patent Pending US 2016-0313425
Publications
Micromagnetic resonance relaxometry for rapid label-free malaria diagnosis
Nature Medicine, VOLUME 20, NUMBER 9, SEPTEMBER 2014, p 1069

Applications

  • Diagnosis of malaria parasitemia
  • Diagnosis of Diabetes Mellitus
  • Monitoring of malaria recurrence
  • Rapid detection and quantification of harmful methemoglobin (oxidized form of ferum in blood)
  • Rapid detection and quantification of deoxygenated red blood cells in whole blood
  • Rapid detection and quantification sickle cells / anemia

  • Rapid detection and quantification of cells or objects, which are paramagnetic in nature
  • Rapid detection and quantification of magnetically-labeled cells

Problem Addressed

Sensitive, quantitative and rapid detection of diseased cells such as Plasodium spp. infected red blood cells in blood or cells and plasma affected by Diabetes Mellitus.

Technology

A major challenge in disease diagnostics is obtaining sensitive, quantitative diagnostic results, preferably in real-time and in an inexpensive manner. Here, a new technique for sensitive, quantitative and rapid detection of parasitemia is developed, by means of microfluidic-based magnetic resonance relaxometry (MRR). This technique can be applied to a wide range of diseases.

As one example, during the intra-erythrocytic cycle, malaria parasites catabolize large amount of cellular hemoglobins and convert them into hemozoin crystallites. These hemozoin crystallites have relatively large paramagnetic susceptibility and are thus able to induce substantial changes in the transverse relaxation rate of proton nuclear magnetic resonance (NMR) of red blood cells (RBCs). They are therefore a 'natural biomarker' to quantify the parasitemia level. Using an inexpensive bench-top 0.5 Tesla MRR system, it is shown that with minimal sample preparation steps and without chemical labeling, a parasitemia level of as low as 0.0875% in 300 nL of RBCs (in less than 1 microliter of whole blood) can be detected within a few seconds of scanning time and the whole assay can be completed within minutes. This rapid quantification of malaria parasitemia can help to address many issues in existing diagnostic methods such as the Giemsa-stained blood smear microscopy or lateral-flow rapid diagnostics kits based on immunochromatography.

Another application for this device is found in the diagnosis of Diabetes Mellitus (DM). In DM, a major pathological effect is oxidative-nitrosative stress (ONS), which causes many of the secondary complications of diabetes. ONS changes the redox reduction-oxidation states of plasma/erythrocytes, thereby changing their magnetic properties, allowing measurement by the MRR system. This technique allows ex-vivo tests on plasma/RBCs for deep-phenotyping of an individual’s oxidative status, susceptibility and capacity.

Advantages

  • Minimal and fast sample preparation steps
  • High volume sensitivity
  • Low cost
  • Real-time analysis