# US 2018/0023111 A1 · Apparatus for characterizing biological objects > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0023111 A1 - Document ID: US20180023111A1 - Status: Published application - Kind: A1 - Application number: 15/724,816 - Filed: 2017-10-04 - Published: 2018-01-25 - Earliest claimed: 2010-06-09 - Assignees: CellTool GmbH - Applicants: CellTool GmbH - Inventors: Raimund Schütze; Karin Schütze - Web page: https://patentgrep.com/patent/US20180023111A1 ## CPC - C12Q 1/04: Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} - C12Q 1/025: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics (antimicrobial activity C12Q1/18)} - G01N 15/1468: {with spatial resolution of the texture or inner structure of the particle} - G01N 21/453: {Holographic interferometry (for dimensional measurements G01B9/021 - G01B9/029)} - G01N 21/65: Raman scattering - G03H 1/0443: {Digital holography, i.e. recording holograms with digital recording means (holobject computation G03H1/0866)} - G01J 3/44: Raman spectrometry; Scattering spectrometry {; Fluorescence spectrometry} - G01N 15/1484: {microstructural devices} - G01N 15/149: specially adapted for sorting particles, e.g. by their size or optical properties - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - G03H: HOLOGRAPHIC PROCESSES OR APPARATUS (holograms, e.g. point holograms, used as ordinary optical elements G02B5/32; producing stereoscopic or other three-dimensional effects G02B30/00; diffraction-grating systems G02B27/44; systems using moiré fringes G02B27/60; optical logic elements G02F3/00; stereo-photography G03B35/00; photosensitive materials or processes for photographic purposes G03C; {stereo-photographic or similar processes G03C9/00}; apparatus for processing exposed photographic materials G03D; analogue computers performing mathematical operations with the aid of optical elements G06E3/00; authentication by radiation, of concealed information carried by holograms or diffraction gratings G06K19/16; holographic storage G11B7/0065, G11C13/04; {stereoscopic or other three dimensional effects in television systems H04N13/00}) - G01J: MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY (light sources F21, H01J, H01K, H05B; investigating properties of materials by optical means G01N) ## Abstract In order to quantitatively characterize biological objects, for example individual cells, a stimulus is applied to a biological object (8) in a contactless fashion. A measurement and a further measurement are performed on the biological object (8) in order to ascertain a response of the biological object (8) to the stimulus, wherein the measurement and the further measurement comprise detecting Raman scattering on and/or in the biological object (8) and/or capturing data using digital holographic microinterferometry (DHMI). The biological object (8) is characterized according to a result of the measurement and is sorted if needed. The stimulus can be applied by means of a laser beam that creates optical tweezers or an optical trap, by means of ultrasonic waves or an electric or magnetic radio frequency field. ## Claims ### Claim 1 An apparatus for characterizing a biological object, comprising a device for holding a biological object in a position where a stimulus can be applied to the biological object; a measurement device for performing a measurement on the biological object to ascertain a response of the biological object to the stimulus; wherein the measurement device is configured for data acquisition by a detection of Raman scattering on the biological object; wherein the measurement device is further configured for ascertaining the response of the biological object to the stimulus, said measurement device performing a measurement comprising a detection of the Raman scattering before application of the stimulus, and performing a further measurement comprising a further detection of the Raman scattering after or during application of the stimulus; and an evaluation logic configured to compare results of the measurement performed before application of the stimulus and results of the further measurement performed after or during application of the stimulus, and to characterize the biological object as a function of a comparison of the results of the measurement and of the further measurement. ### Claim 2 (depends on 1) The apparatus according to claim 1, wherein the device for holding the biological object holds the biological object in such a way that there is no contact between the biological object and the stimulus. ### Claim 3 (depends on 1) The apparatus according to claim 1, wherein the device for holding the biological object in such a way that there is no contact between the biological object and the stimulus during Raman measurement. ### Claim 4 (depends on 1) The apparatus according to claim 1, wherein the apparatus further comprises an optical microscope. ### Claim 5 (depends on 1) The apparatus according to claim 1, wherein the apparatus further comprises a laser source that provides an excitation beam to induce the Raman scattering. ### Claim 6 (depends on 5) The apparatus according to claim 5, wherein said excitation beam additionally acts as optical tweezers for holding or positioning or sorting the biological object ### Claim 7 (depends on 5) The apparatus according to claim 5, wherein the laser source is configured to simultaneously arrest the biological object during Raman spectra acquisition to allow Raman measurements of the biological object in solution. ### Claim 8 (depends on 1) The apparatus according to claim 1, further comprising an optical source that generates a stimulus for the biological object. ### Claim 9 (depends on 1) The apparatus according to claim 1, wherein the measurement device comprises a Raman device for detecting a Raman scattering on the biological object. ### Claim 10 (depends on 4) The apparatus according to claim 4, wherein the measurement device comprises a Raman device for detecting a Raman scattering on the biological object; and wherein the Raman device is configured to controllably move a focus of an excitation beam of the Raman device in three orthogonal spatial directions independently of a focus of a beam path of the optical microscope. ### Claim 11 (depends on 10) The apparatus according to claim 10, wherein the Raman device comprises: one or more lenses; and a positioning device coupled to the one or more lenses and configured to controllably move the one or more lenses in the three orthogonal spatial directions in a controllable manner, and to controllably move the focus of the excitation beam of the Raman device in the three orthogonal spatial directions independently of a focus of the optical microscope. ### Claim 12 (depends on 1) The apparatus according to claim 1, further comprising: an electronically controllable beam deflection device configured to scan a laser beam of the apparatus to generate the stimulus or Raman scattering over a plurality of positions. ### Claim 13 (depends on 1) The apparatus according to claim 1, further comprising: a microfluidic system that upholds or transports or sorts the biological object. ### Claim 14 (depends on 13) The apparatus according to claim 13, further comprising: an optical trap that holds or transports or sorts the biological object. ### Claim 15 (depends on 13) The apparatus according to claim 13, further comprising: an optical trap that holds or transports or sorts the biological object without physical contact within the microfluidic device. ### Claim 16 (depends on 13) The apparatus according to claim 13, wherein the microfluidic system comprises a closed fluid loop for transporting biological objects before and after the measurement is performed. ### Claim 17 (depends on 16) The apparatus according to claim 16, wherein the closed fluid loop of the microfluidic system is configured to continuously transports the biological object. ### Claim 18 (depends on 1) The apparatus according to claim 1 configured to perform a method for characterizing the biological object, wherein when the stimulus is applied to the biological object, plural measurements are carried out on the biological object to ascertain the response of the biological object to the stimulus, and wherein, to ascertain the response, the measurement which comprises the detection of the Raman scattering is performed on the biological object prior to application of the stimulus, and the further measurement which comprises the further detection of the Raman scattering is performed on the biological object after or during application of the stimulus, and wherein a comparison of results of the measurement and the further measurement is performed, and the biological object is characterized as a function of the comparison of the results of the measurement and the further measurement. ### Claim 19 An apparatus for characterizing a biological object comprising: a microfluidic system that transports a biological object; a device for generating a stimulus on the biological object in the microfluidic system; a measurement device that performs a measurement on the biological object to ascertain a response of the biological object to the stimulus, wherein the measurement device is configured for enrichment or sorting of the biological object using a second laser source to isolate and eject a desired biological sample for further analysis; and an evaluation logic configured to compare results of the measurement performed before application of the stimulus and results of the further measurement performed after or during application of the stimulus, and to characterize the biological object as a function of a comparison and results of the measurement and the further measurement. ### Claim 20 (depends on 19) The apparatus according to claim 19, wherein the measurement device comprises a Raman device for detecting the Raman scattering on the biological object. ### Claim 21 (depends on 20) The apparatus according to claim 20, wherein the measurement device further comprises an optical microscope; and wherein the Raman device is configured to controllably move a focus of an excitation beam of the Raman device in three orthogonal spatial directions independently of a focus of a beam path of the optical microscope. ### Claim 22 (depends on 21) The apparatus according to claim 21, wherein the Raman device comprises: a lens; and a positioning device coupled to the lens and configured to controllably move the lens in the three orthogonal spatial directions in a controllable manner to controllably move the focus of the excitation beam of the Raman device in the three orthogonal spatial directions independently of the focus of the optical microscope. ### Claim 23 (depends on 19) The apparatus according to claim 19, further comprising: an electronically controllable beam deflection device for scanning a laser beam to generate the stimulus or a measurement beam of the measurement device over a plurality of positions. ### Claim 24 (depends on 19) The apparatus according to claim 19, wherein the microfluidic system comprises a closed fluid loop adapted to transport the biological object before the measurement is performed.