Devices


1h in vivo-like phenotypic screening device

1.  Device for solid cells MitoPOM (Mitochondria polarization monitor

MitoPOM is an in vivo-like phenotypic screening device for solid cells against drugs (candidates) such as anti-cancer and bioactive compounds. The device analyzes 12 samples at once. The operation is semi-automatic.

Conventional technology of in vivo-like test is based on expensive endpoint assay of 3D cell culture with extracellular matrix necessitating time-consuming experimental process (2-4 weeks) and labeling agents causing interference with a target compound that provide low reliability. The previous device methods depend on the pharmaceutical mode of action, and give no relation to the conventional method. And a separate set of experiment is required to obtain both efficacy and toxicity results. Our new technology overcomes these all problems sensing dynamic cellular reaction against target compound(s) by laser.

The technological break points are as follows.

  1. New device is developed for real-time monitoring of mitochondrial polarization status within live cells without both labeling and invasion.
  2. Early mitochondrial polarization change rate after addition of target compound (s) is revealed as a key to quantitatively predict the final compound efficacy and toxicity against live cells.
  3. 3D cell activity is obtained by conditioning 2D attached cells covered by extracellular matrix for short time with no cell division.

Advantages of our technology are as follows.

  1. Easy handling
  2. Medium exchange free
  3. Rapid decision duration (1h)
  4. Label free
  5. Small test error
  6. Limited cells used (1000)
  7. Regardless to compound mode of action
  8. High reliability in polypharmacy
  9. Physiological concentration evaluation
  10. Compatibility with conventional results
  11. Simultaneous evaluation of efficacy and toxicity

MitoPOM provides in vivo-like test (screening) against the following targets using human live cells.

    1. Anti-cancer
    2. Pro-fat burning
    3. Pro-metabolism
    4. Anti-aging
    5. Pro-skin turn over
    6. Pro-body temp

The expected application for MitoPOM relates to mitochondria and its examples are as follows.

  1. Anti-Alzheimer disease
  2. Anti –diabetes
  3. Anti-epileptic
  4. Pro -hair restoration
  5. Pro-skin whitening
  6. Anti-skin wrinkling

MitoPOM is suitable for drug repositioning, and searches synergistic effect and rescue effect for combination use of compounds. This enables regeneration of old or discarded drugs to be patented. Furthermore, MitoPOM well determines drug efficacy and toxicity in case of drug delivery. Moreover, MitoPOM requires no cell culture and is very effective for new drug development especially in using stem cell disease model necessitating long term cell culture causing difficulty to keep the healthy cell condition.

 

Build-to-order manufacturing product, Price: from 600,000 USD (excluding TAX and shipping)

 

2.  Device for floating cells DriaPOM (Mitochondria polarization monitor)

DriaPOM has the same basics as MitoPOM, but DriaPOM is specialized for floating cells. The device analyzes 6 samples at once. The operation is semi-automatic. The therapy of acute lymphocytic leukemia is based on anti-cancer drug chemotherapy. Conventional drug screening for acute lymphocytic leukemia depends on genomics achieved within 1h and the therapy is started. The successful drug matching brings maximum 80% saving yield in case of small child. However, in case of adolescent, the saving yield is much lower. This insufficiency is often caused by abnormal genomic mutation. The selection of anti-cancer drug is extremely important for acute lymphocytic leukemia, but the conventional screening is not enough similarly for solid cancers. DriaPOM predicts both efficacy and toxicity of 6 species of anti-cancer drugs to accelerate remission at initial treatment.

DriaPOM provides in vivo-like test (screening) against anti-cancer using human live floating cells.

The expected application for DriaPOM relates to mitochondria and its example is natural killer (NK) cells of immune system.

 

Build-to-order manufacturing product, Price: from 600,000 USD (excluding TAX and shipping)

 

Key publications

Kosaihira, A. and Ona, T. Rapid and quantitative method for evaluating the personal therapeutic potential of cancer drugs. Anal Bioanal Chem, 391:1889 (2008).

Ona, T., Nishijima, H., Kosaihira, A. and Shibata, J. Development of cell-based quantitative evaluation method for cell cycle-arrest type cancer drugs for apoptosis by high precision surface plasmon resonance sensor. Biophotonics 9:69910R (2008).

Nishijima, H., Kosaihira, A., Shibata, J. and Ona, T. Development of signaling echo method for cell-based quantitative efficacy evaluation of anti-cancer drugs in apoptosis without drug presence using high-precision surface plasmon resonance sensing. Anal Sci, 26:529 (2010).

Ona, T. and Shibata, J. Advanced dynamic monitoring of cellular status using label-free and non-invasive cell-based sensing technology for the prediction of anti-cancer drug efficacy. Anal Bioanal Chem, 398:2505 (2010).

Ona, T. and Shibata, J. Label-free, rapid and reliable new chemosensitivity test for physiological concentration of anti-cancer drug: evaluation within 1h. J Pharm Sci, 121:132 (2013).

Ona, T. and Shibata, J. Label-free, rapid and reliable new cell-based assay for physiological concentration of anti-cancer and anti-metabolic syndrome compounds: evaluation within 1h. J Pharm Sci, 121:159 (2013).

Ona, T. and Shibata, J. Cell-based rapid and quantitative toxicity and efficacy monitoring in consecutive before and after the compound metabolism within liver for two ginger compounds at physiological concentration. ALTEX Proc, 3:24 (2014).

Ona, T. and Shibata, J. Rapid in vivo-like efficacy and toxicity evaluation of target compound using mitochondria activity change within epidermis keratinocyte cell. FRAGRANCE J, 42:50 (2014).

 

IP rights

Ona, T. and Kosaihira, A. Method of screening substance with anticancerous activity and apparatus therefor. JP2005-17081A (2005); WO 2005/001472 A1 (2005).

Ona, T. and Kosaihira, A. Monitoring of intercellular mitochondrial polarization. WO2007/069692 A1 (2007); CN 200680052043.8 (2008); EP 1 961 824 A1 (2008); US 2011/0003321 A1 (2011); JP2012-93369A (2012).

Ona, T., Method for activating two-dimensional cultured cells similarly to three-dimensional culture or in vivo, and use thereof. WO 2013/039112 A1 (2013).

 

3.  Device for stem cells DiffPOM (Prediction of differentiation status of stem cell at the initiation by mitochondrial polarization monitoring)

DiffPOM is based on the in vivolike test technology described above. DiffPOM enables the prediction of next or final differentiation status of stem cell at the initiation. The monitoring of mitochondrial polarization status including distribution within cells is revealed as a key to predict the destination of cells by differentiation.

Much attention is paid to utilize stem cells such as iPS cells for regenerative therapy in organ diseases, which will replace organ and artificial organ transplantation. To achieve this, the produced mature functional cells should possess high in purity, safety, and therapeutic effect.

Conventional method to obtain target cells is based on the test of staining cells using labeling agents sometimes conjugated with antibiotics using isolated cells from the culture plate. Then the cells are analyzed by a high energy scanning instrument such as a flow cytometer. However, this will bring toxicity to the target cells by the procedure of labeling agents, high energy scanning and cell isolation. Furthermore, this will not apply to all screened cells to cause contamination of not-targeting cells and the screened cells are unknown in the nature of activity.

Target cells can be screened by our technology without labeling and cell-invasion, rapidly. Our technology does not require isolation of cells from a culture plate and tests all cells used to avoid contamination and to achieve high purity. Furthermore, high safety is kept because future cancerous cells are screened by our technology. Additionally, high activity cells are screened by monitoring mitochondrial activity.

By using DiffPOM , efficient and safe regenerative therapy is expected. DiffPOM will help creating organs from stem cells and will achieve quality control of stem cells efficiently.

 

Engineer -to-order manufacturing product, Price: from 1,200,000 USD (excluding TAX and shipping)

 

IP rights

Nomura, M., Matsubara, E., Ona, T. Determination system, selection system, determination method, cell production method, program, and recording medium. JP2009-122016A (2009).