Optical measuring apparatus and method for the analysis of samples contained in liquid drops

An optical measuring method of analyzing samples contained in liquid drops (2) that are provided by liquid handling systems (3),

• wherein the method comprises the steps of:
• (a) providing a liquid handling system (3) which comprises at least one liquid handling tip (4) with a liquid handling axis (5) and with a liquid handling orifice (6) at a distal end (7) of the liquid handling tip (4), the liquid handling axis (5) extending inside the liquid handling tip (4) and penetrating the liquid handling orifice (6);
• the liquid handling system (3) further comprising a pump (39) that is controlled by a central processor (44) of the liquid handling system (3), the pump (39) being operatively connected to the liquid handling tip (4) via a pressure line (40);
• (b) providing a liquid drop (2) that is suspended at the liquid handling orifice (6) of the liquid handling tip (4) of the liquid handling system (3) in a position where the liquid drop (2) is penetrated by a first optical axis (14) that extends essentially perpendicular to the liquid handling axis (5);
• (c) providing an optical measuring apparatus (1) that comprises a processor (13), a light source (8), a detector (10), and an optics system (43) with first optical elements (18) for transmitting irradiation light (9) from the light source (8) to the liquid drop (2) and with second optical elements (19) for transmitting sample light (11) from the liquid drop (2) to the detector (10);
• the light source (8) and the liquid drop (2) defin-ing the first optical axis (14) of the first optical elements (18) of the optics system (43);
• a first and second air space (15,16) separating the liquid drop (2) from the light source (8) and detector (10) and their associated first and second optical elements (18,19) that thus do not contact the liquid drop (2);
• and
• (d) providing a second light source (37), a collimating lens (38), and an imaging chip (32) of the optical measuring apparatus (1) on a third optical axis (35);
• wherein the second light source (37), collimating lens (38), and imaging chip (32) of the optical measuring apparatus (1) are used for imaging and for controlling the size and/or position of the liquid drop (2);
• wherein the size of the liquid drop (2) is adapted with respect to at least one optical element (18,19) of the optics system (43) by the central processor (44) of the liquid handling system (3) as controlled by the processor (13) of the optical measuring apparatus (1) and by the pump (39) of the liquid handling system (3);
• and wherein the following steps are being carried out:
• (e) irradiating the liquid drop (2) with irradiation light (9) originating from the light source (8);
• (f) measuring sample light (11) arriving at the detector (10) from the liquid drop (2) and providing measurement signals (12) with the detector (10);
• and
• (g) processing with the processor (13) that is operatively connected to the detector (10) the measurement signals (12) provided by the detector (10).

An optical measuring apparatus (1) configured for the analysis of samples contained in liquid drops (2) that are provided by a liquid handling system (3) which comprises at least one liquid handling tip (4) with a liquid handling axis (5) and with a liquid handling orifice (6) at a distal end (7) of the liquid handling tip (4), the liquid handling axis (5) extending inside the liquid handling tip (4) and penetrating the liquid handling orifice (6);

• the optical measuring apparatus (1) comprising a light source (8) configured for providing irradiation light (9) for irradiating a liquid drop (2) of a liquid sample (30);
• a detector (10) configured for measuring sample light (11) arriving from said liquid drop (2) and for providing measurement signals (12) that represent the measured sample light (11);
• an optics system (43) with first optical elements (18) for transmitting the irradiation light (9), and a processor (13) connected to the detector (10) and configured to accept and process the measurement signals (12) provided by the detector (10),
• wherein the light source (8) and the liquid drop (2) define a first optical axis (14) of the first optical elements (18) of the optics system (43) that extends essentially perpendicular to the liquid handling axis (5), the liquid drop (2) being provided by the liquid handling system (3) and being suspended at the liquid handling orifice (6) of the liquid handling tip (4) in a position where the liquid drop (2) is penetrated by the first optical axis (14),
• wherein the liquid drop (2) is physically separated from the optics system (43) of the optical measuring apparatus (1) and is physically touched only by the liquid handling tip (4) of the liquid handling system (3) and the liquid sample (30) inside the liquid handling tip (4), the light source (8) with the first optical elements (18) being thus separated from the liquid drop (2) by a first air space (15) and the detector (10) being thus separated from the liquid drop (2) by a second air space (16),
• wherein the optical measuring apparatus (1) comprises an imaging chip (32) that is configured for detecting an actual optical pathlength of the light penetrating the liquid drop (2) or for controlling the size and position of the liquid drop (2).