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Sci Adv. 2016 Jun 10;2(6):e1600077. doi: 10.1126/sciadv.1600077. eCollection 2016 Jun.

Ultrasensitive interferometric on-chip microscopy of transparent objects.

Author information

1
ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels (Barcelona), Spain.
2
ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels (Barcelona), Spain.; Department of Signal Theory and Communications, Universitat Politècnica de Catalunya, 08034 Barcelona, Spain.
3
ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels (Barcelona), Spain.; ICREA-Institució Catalana de Recerca i Estudis Avançats, Passeig Lluís Companys 23, 08010 Barcelona, Spain.

Abstract

Light microscopes can detect objects through several physical processes, such as scattering, absorption, and reflection. In transparent objects, these mechanisms are often too weak, and interference effects are more suitable to observe the tiny refractive index variations that produce phase shifts. We propose an on-chip microscope design that exploits birefringence in an unconventional geometry. It makes use of two sheared and quasi-overlapped illuminating beams experiencing relative phase shifts when going through the object, and a complementary metal-oxide-semiconductor image sensor array to record the resulting interference pattern. Unlike conventional microscopes, the beams are unfocused, leading to a very large field of view (20 mm(2)) and detection volume (more than 0.5 cm(3)), at the expense of lateral resolution. The high axial sensitivity (<1 nm) achieved using a novel phase-shifting interferometric operation makes the proposed device ideal for examining transparent substrates and reading microarrays of biomarkers. This is demonstrated by detecting nanometer-thick surface modulations on glass and single and double protein layers.

KEYWORDS:

digital interference contrast microscopy; high-throughput biodetection; interferometry; lens-free imaging; on-chip sensing

PMID:
27386571
PMCID:
PMC4928994
DOI:
10.1126/sciadv.1600077
[Indexed for MEDLINE]
Free PMC Article

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