Abstract
Traditional high-throughput screening (HTS) is carried out in centralized facilities that require extensive robotic liquid and plate handling equipment. This model of HTS is restrictive as such facilities are not accessible to many researchers. We have designed a simple microarray platform for cell-based screening that can be carried out at the benchtop. The device creates a microarray of 2100 individual cell-based assays in a standard microscope slide format. A microarray of chemical-laden hydrogels addresses a matching array of cell-laden microwells thus creating a microarray of sealed microscale cell cultures each with unique conditions. We demonstrate the utility of the device by screening the extent of apoptosis and necrosis in MCF-7 breast cancer cells in response to exposure to a small library of chemical compounds. From a set of screens we produced a rank order of chemicals that preferentially induce apoptosis over necrosis in MCF-7 cells. Treatment with doxorubicin induced high levels of apoptosis in comparison with staurosporine, ethanol, and hydrogen peroxide, whereas treatment with 100 μM ethanol induced minimal apoptosis with high levels of necrosis. We anticipate broad application of the device for various research and discovery applications as it is easy to use, scalable, and can be fabricated and operated with minimal peripheral equipment.
| Original language | English |
|---|---|
| Pages (from-to) | 4118-4125 |
| Number of pages | 8 |
| Journal | Analytical Chemistry |
| Volume | 83 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2011 Jun 1 |
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ASJC Scopus subject areas
- Analytical Chemistry
Cite this
Drug-eluting microarrays for cell-based screening of chemical-induced apoptosis. / Kwon, Cheong Hoon; Wheeldon, Ian; Kachouie, Nezamoddin N.; Lee, Seung Hwan; Bae, Hojae; Sant, Shilpa; Fukuda, Junji; Kang, Jeong Won; Khademhosseini, Ali.
In: Analytical Chemistry, Vol. 83, No. 11, 01.06.2011, p. 4118-4125.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Drug-eluting microarrays for cell-based screening of chemical-induced apoptosis
AU - Kwon, Cheong Hoon
AU - Wheeldon, Ian
AU - Kachouie, Nezamoddin N.
AU - Lee, Seung Hwan
AU - Bae, Hojae
AU - Sant, Shilpa
AU - Fukuda, Junji
AU - Kang, Jeong Won
AU - Khademhosseini, Ali
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Traditional high-throughput screening (HTS) is carried out in centralized facilities that require extensive robotic liquid and plate handling equipment. This model of HTS is restrictive as such facilities are not accessible to many researchers. We have designed a simple microarray platform for cell-based screening that can be carried out at the benchtop. The device creates a microarray of 2100 individual cell-based assays in a standard microscope slide format. A microarray of chemical-laden hydrogels addresses a matching array of cell-laden microwells thus creating a microarray of sealed microscale cell cultures each with unique conditions. We demonstrate the utility of the device by screening the extent of apoptosis and necrosis in MCF-7 breast cancer cells in response to exposure to a small library of chemical compounds. From a set of screens we produced a rank order of chemicals that preferentially induce apoptosis over necrosis in MCF-7 cells. Treatment with doxorubicin induced high levels of apoptosis in comparison with staurosporine, ethanol, and hydrogen peroxide, whereas treatment with 100 μM ethanol induced minimal apoptosis with high levels of necrosis. We anticipate broad application of the device for various research and discovery applications as it is easy to use, scalable, and can be fabricated and operated with minimal peripheral equipment.
AB - Traditional high-throughput screening (HTS) is carried out in centralized facilities that require extensive robotic liquid and plate handling equipment. This model of HTS is restrictive as such facilities are not accessible to many researchers. We have designed a simple microarray platform for cell-based screening that can be carried out at the benchtop. The device creates a microarray of 2100 individual cell-based assays in a standard microscope slide format. A microarray of chemical-laden hydrogels addresses a matching array of cell-laden microwells thus creating a microarray of sealed microscale cell cultures each with unique conditions. We demonstrate the utility of the device by screening the extent of apoptosis and necrosis in MCF-7 breast cancer cells in response to exposure to a small library of chemical compounds. From a set of screens we produced a rank order of chemicals that preferentially induce apoptosis over necrosis in MCF-7 cells. Treatment with doxorubicin induced high levels of apoptosis in comparison with staurosporine, ethanol, and hydrogen peroxide, whereas treatment with 100 μM ethanol induced minimal apoptosis with high levels of necrosis. We anticipate broad application of the device for various research and discovery applications as it is easy to use, scalable, and can be fabricated and operated with minimal peripheral equipment.
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U2 - 10.1021/ac200267t
DO - 10.1021/ac200267t
M3 - Article
C2 - 21476591
AN - SCOPUS:79957933734
VL - 83
SP - 4118
EP - 4125
JO - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 11
ER -